Protein and peptide vaccines targeting methanogens
Vaccines targeting methanogen cell surface antigens in ruminants surprisingly reduce methane and hydrogen emissions, enhancing productivity and treating associated diseases, addressing the limitations of existing inhibition methods.
Patent Information
- Authority / Receiving Office
- AU · AU
- Patent Type
- Applications
- Current Assignee / Owner
- ARKEA BIO CORP
- Filing Date
- 2025-01-10
- Publication Date
- 2026-07-23
AI Technical Summary
Existing methods to inhibit methanogens in ruminants for reducing methane emissions are ineffective, non-selective, and unsafe, particularly in extensive production environments where precise daily dosages are difficult to maintain.
Development of vaccines comprising polypeptides and/or peptide fragments targeting methanogen cell surface antigens to induce immune responses and reduce methane and hydrogen production, applicable in both intensive and extensive production environments.
The vaccines effectively reduce methane and hydrogen emissions, improve feed conversion efficiency, and enhance productivity in ruminants, while also treating diseases associated with methanogens such as periodontal disease and lactic acidosis.
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Abstract
Description
CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 63 / 619572, filed January 10, 2024; and U.S. Provisional Application No. 63 / 645238, filed May 10, 2024. The entire contents of each of said applications are incorporated herein in their entirety by this reference. INCORPORATION BY REFERENCE OF SEQUENCE LISTING The application contains a Sequence Listing which has been submitted electronically in the form of an XML file, created January 3, 2025, and named ARD-00825_SL.xml (93,100,973 bytes), the contents of which are incorporated herein by reference in their entirety. BACKGROUND OF THE INVENTION Methane (CH4) is the world’s second most abundant greenhouse gas after carbon dioxide (CO2), accounting for 16% of total greenhouse gas emissions. Livestock emissions, in particular, account for -32% of all anthropogenic CH4 emissions - equating to -6% of all CO2 equivalents (CO2e) of greenhouse gas emissions and -3 billion Tonnes / yr of CO2e. CH4 is a powerful greenhouse gas with a potential global warming effect -28-fold higher than that of CO2 over a 100 year period and -80-fold higher than that of CO2 over a 20 year period. Furthermore, CH4 has an atmospheric half-life of-10 years, thus reducing enteric CH4 emissions could have an immediate and dramatic effect on limiting the rate of global warming, which would be of great significance to efforts to reduce global greenhouse gas emissions. Furthermore, CH4 emissions also represent energy losses during ruminant production. On average, approximately 2-12% of the energy consumed in feed is lost in the form of CH4 emissions. For rumiants, CH4is predominantly formed in the ruminant fore-stomach (rumen) by methanogens, a subgroup of the Archaea. During normal rumen function, plant material is broken down by fiber-degrading microorganisms and fermented mainly to volatile fatty acids, ammonia, hydrogen (H2) and CO2. Ruminal methanogens principally use H2 to reduce CO2 to CH4 in a series of reactions that are coupled to ATP synthesis. Additional biochemical pathways to produce CH4 from acetate and methanol / methylamine substrates are also present, but represent a lower fraction of the total CH4 biosynthesis in the rumen. Attempts have been made to inhibit the action of methanogens in the rumen using a variety of interventions but most have failed, or were met with only limited success, due to low efficacy, poor selectivity, toxicity of compounds against the host, and / or build-up of resistance to anti-methanogen compounds. Further most solutions, e.g., feed additives and antibiotics, are only applicable to intensive production environments where the animal’s diet can be effectively controlled to ensure precise daily dosages of the intervention. These solutions are, thus, not effective in extensive, grass-fed production environments where the animals a rarely handled and / or operations where feed cannot readily be mixed daily. Accordingly, there is a great need in the art for effective, selective, and safe compositions and methods for inhibiting methanogens. SUMMARY OF THE INVENTION The present invention is based, at least in part, on the discovery that vaccines of the present disclosure (e.g., vaccines comprising at least one polypeptide and / or at least one peptide fragment) against at least one cell surface antigen or a fragment thereof (e.g., antigenic fragment, epitope) of at least one methanogen, when administered to a subject (e.g., animal, ruminant, human), are surprisingly effective in inducing immunue response and antibody production against the methanogen, and reducing the methane production in the subject. Previous attempts to vaccinate ruminants and reduce methane production have been largely unsuccessful. Research on a vaccine targeting methanogen(s) has cost between $4 million to $5 million a year for more than 20 years. Unfortunately, while the vaccination was able to induce immune response and production of antibodies against methanogens, it was not possible to induce production of a consistently large amount of antibodies; and to produce effective antibodies that can neutralize the growth of the methanogen and / or the production of methane. Thus, vaccination to reduce methane and / or hydrogen production in a subject (e.g., animal, ruminant, human) remained a failure. Surprisingly, the vaccine compositions and methods of the present disclosure are surpringly effective in reducing the CH4 emission reductions. In addition to CH4 emission reductions, vaccine compositions and methods of the present disclosure have shown surprising and unexpected reductions in emitted H2 following treatment. These results are both surprising and unexpected as reductions in CH4 following treatment with small molecule inhibitors and feed additives have contrarily shown increases in H2 emissions. The reduction in both CH4 and H2 emissions suggest that the vaccine compositions and methods of the present disclosure have utility in improving the feed conversion efficiency and thereby the productivity of treated animals, e.g., increasing the production and / or ruminal concentration of one or more volatile fatty acids (e.g., propionate, butyrate, acetate) in the rumen of the animal, increasing the average daily gain of the animal, reducing the dry matter intake of the animal, reducing the feed requirements of the animal during lactation, and / or increasing the milk production of the animal. Increasing productivity of treated animals can further reduce the carbon intensity of resultant animal products (e.g., milk and meat) as treated animals are not only emit less CH4 but also produce more product per animal. Thus, the total reduction in carbon intensity of animal-derived products from animals treated with a vaccine composition of the present disclosure may can be calculated as the composite of the CH4 reduction of the animal following treatment in combination with the reduced carbon footprint associated with growing and maintaining those animals (e.g., less total feed, manure, urine, etc.). The vaccine compositions and methods of the present disclosure are useful beyond reducing the methane emission in ruminants. It is well documented that methanogens are associated with various diseases, including a periodontal disease, inflammatory bowel disease (IBD), irritable bowel syndrome (ISB), IBS-C, small instestinal bacterial overgrowth (SIBO), colorectal cancer, obesity and metabolic syndrome, diverticulosis and diverticulitis, gingivitis, and bloat. Thus, the vaccine compositions and methods of the present disclosure have utility in treating these diseases in animals including humans. The vaccines of the present disclosure also provide a surprising and unexpected effect on lactic acidosis (e.g., reducing rumen lactate, increasing pH, or combination thereof). Therefore, the vaccine compositions methods of the present disclosure have utility in treating diseases associated with elevated, increased, or severe lactic acidosis, e.g., liver abscess. BRIEF DESCRIPTION OF FIGURES Fig. lA-Fig. IB show schematic diagrams representing the relative abundance of methanogen species across geographies and herds. The diagrams indicate that methanogen populations are relatively stable across geographies and herds. For example, Methanobrevibacter gottschalkii comprises -30-40% of ruminal methanogens globally; thus, a cell vaccine could provide an effective global solution for reducing the amount of methane generated by ruminants. Fig-2 A subway diagram of our improved metatdenovo pipeline. Fig. 3 Heatmap of the expression values of 192 genes of interest within the M. gottchalkii transcriptome. Each row represents the expression of a single gene and is labeled by its corresponding protein ID. Each column represents one AT. gottschalkii monoculture harvested in exponential phase. Row annotations include any enriched GO terms (GOgroup) or Pfams (Pfamgroup) and the number of mass spectrometry samples in which the protein was found MS Samples). Genes with multiple enriched GO terms or Pfams are labeled as such for simplicity. Fig. 4 Heatmap of the normalized and transformed expression values of the metaT de novo assembly contigs that best matched to a gene of interest. Each row represents the expression of a single contig and is labeled by the corresponding gene of interest’s protein ID and the contig ID, separated by an underscore. Each column represents one rumen sample harvested under different conditions. Fig- 5 shows a schematic diagram that illustrates vaccination and post-vaccination testing of a ruminant (e.g., a cow). Fig. 6A-Fig. 6C show schematic diagrams that illustrate exemplary tests performed for a ruminant vaccinated with a polypeptide and / or peptide vaccine of the present disclosure. Fig. 6A shows quantifying Ig antibody in serum and saliva of a vaccinated ruminant. The antibody is evaluated for methanogen binding to methanogens (e.g., affinity, specificity, etc.) and / or its effect on the fitness of methanogens (e.g., proliferation, methane production, etc.) upon binding. Fig. 6B shows measuring the amount of methane produced by a vaccinated ruminant using the GreenFeed system (C-lock Inc., Rapid City, South Dakota). Fig. 6C shows evaluation of the changes in the rumen microbiome in a vaccinated ruminant. The 16S rRNA sequencing identifies the presence and the amount of specific methanogens. Fig- 7 shows a schematic diagram of an exemplary instrument (e.g., GreenFeed) that measures the methane produced from the rumen of a ruminant. Fig. 8 is a schematic of a biochemical pathway and enzymes for the production of methane from acetate (i.e., the acetoclastic pathway), hydrogen and carbon dioxide (i.e., the hydrogenotrophic pathway), and methanol and derivatives thereof (i.e., the methylotrophic pathway). Fig. 9 is a schematic describing the reduction of methyl-CoM and coenzyme B into methane by methyl-coenzyme M reductase (MCR), a key enzyme present in methane production via the acetoclastic, hydrogenotrophic, and methylotrophic pathways. Fig. 10 is a schematic describing the application of small molecules that affect MCR activity to modulate methane production. Fig. 11A shows a computational pipeline (left) for selection of methanogen cell surface proteins for vaccine production. The pipeline includes collation of all ORFs, filtering based on uniqueness to methanogens, cell localization, and function. A network map of key methanogen cell surface protein functions is shown to the right. Fig. 11B shows a schematic representation of the protein fragments described in Table 21. The amino acid sequence of each folded domain is designated as a “protein fragment” in Table 21, each of which is useful as an antigen for the vaccines of the present disclosure. Fig. 12 is a cross-sectional diagram of the application of a composition for reduction of deleterious atmospheric gases and / or precursors thereof to a flooded ecosystem. Fig. 13 shows aerial delivery of a composition for reduction of deleterious atmospheric gases and / or precursors thereof to a flooded ecosystem. Fig. 14 shows 3NOP concentration (mM) v. adsorbent (~20mM stock solution). Fig. 15 shows 3NOP concentration (mM) v. adsorbent (~8mM stock solution). Fig. 16 shows exemplary multilayer poly electrolyte coatings of 15% activated carbon tablets. Fig. 17 shows exemplary multilayer polyelectrolyte coatings of 25% activated carbon tablets. Fig. 18 shows exemplary multilayer poly electrolyte coatings of 15% activated carbon tablets with 5% sodium lignosulfonate. Fig. 19 shows exemplary multilayer poly electrolyte coatings of 15% activated carbon with 5% hydroxypropyl cellulose. Fig. 20 is a graph showing the release profiled of a silica v. activated carbon adsorbent. Fig. 21 is a table showing the composition of various polycaprolactone-based formulations according to some embodiments of the invention. Fig. 22 is a bar graph showing 3NOP release in mM for exemplary polycaprolactone-based formulations. Fig. 23 is a graph showing normalized 3NOP concentration v. release time in days of exemplary polybutylene succinate-based formulations. Fig. 24 is a bar graph showing 3NOP release (%) from exemplary PEC microcapsules. Samples are prepared with a 3NOP concentration of 100 pM. Final pH solution ~7. K, L, F, and E refer to lysine, leucine, phenylalanine, and glutamic acid, respectively. PSS refers to polystyrene sulfonate. Fig. 24 discloses (KKLF)3 as SEQ ID NO: 79312, (EELF)3 as SEQ ID NO: 79313 and (kKlF)3 as SEQ ID NO: 79314. Fig. 25 is bar graph showing 3NOP release (%) from exemplary PEC microcapsules. Samples are prepared with a 3NOP concentration of 100 pM. Final pH solution ~7. PLR refers to poly (L-arginine), and PLK refers to poly (L-lysine). SLS and PSS refer to sodium lignosulfonate and polystyrene sulfonate. Fig. 26 shows average daily group ADG (kg per day) for individual animals, grouped by treatment group, as described in Example 12. Fig. 27 shows the GreenFeed visitation for all animals, grouped by measurement period, as described in Example 12. Fig. 28 shows the GreenFeed visitation pattern overlaid with maximum local temperature (McGregor, TX) as described in Example 12. Fig. 29 shows visual definition of AA analysis as described in Example 12. Fig. 30 shows AA CH4 production (g / d) for protein antigen formulations, relative to preprime baseline (pO), as described in Example 12. Fig. 31 shows AA CH4 intensity (g / d) for protein antigen formulations, relative to preprime baseline (pO), as described in Example 12. Fig. 32 shows RPF51698.1 ELISA IgG response, average value of treatment groups over time. Treatment groups 9G & 9H have elevated IgG response against RPF51698.1 protein relative to the control group 9A at d28 & d42 (p < 0.001) and d63 (p < 0.01 ). T-tests do not support treatment group 91 being greater than the control group at d42 (p = 0.08), as described in Example 12. Fig. 33 shows ADC46800.1 ELISA IgG response, average value of treatment groups over time. Treatment groups 9G, 9H, & 91 have elevated IgG response against ADC46800.1 protein compared to the control group 9A (p < 0.001 all days except Group 9H d63 p < 0.01). T-tests support a difference in Group 9C d63 (p < 0.05) but do not support a difference in Group 9D d42 (p = 0.2), as described in Example 12. DETAILED DESCRIPTION OF THE INVENTION Provided herein are vaccines (e.g., comprising at least one protein and / or at least one peptide fragment) against at least one cell surface antigen or a fragment thereof (e.g., antigenic fragment, epitope) of at least one methanogen, which are effective in inducing immune response and antibody production against the methanogen antigen, and reducing the methane and / or hydrogen production in subjects. The vaccines of the present disclosure are also useful in treating diseases in subjects (e.g., animals, mammals, ruminants, humans) that are associated with methanogens (e.g., a periodontal disease, Inflammatory Bowel Disease (IBD), irritable bowel syndrome (ISB), IBS-C, small instestinal bacterial overgrowth (SIBO), colorectal cancer, obesity and metabolic syndrome, diverticulosis and diverticulitis, gingivitis, and / or bloat). The vaccines of the present disclosure are also useful in treating diseases in subjects (e.g., animals, mammals, ruminants, humans) that are associated with elevated, increased, or severe lactic acidosis, e.g., liver abscess. DEFINITIONS The articles “a” and “an” are used herein to refer to one or to more than one (i. e. to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element. As used herein, the term "about" when used before a numerical designation, e.g., temperature, time, amount, concentration, and such other, including a range, indicates approximations which may vary by (+) or (-) 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1%. The term “administering” is intended to include routes of administration which allow an agent (e.g., a vaccine composition, an agent that reduces methane production in a subject) to perform its intended function. Examples of routes of administration which can be used include injection (subcutaneous, intravenous, parenteral, intraperitoneal, intrathecal, intradermal, intramuscular, etc.\ oral, inhalation, and transdermal routes. The injections can be bolus injections or can be continuous infusion. Depending on the route of administration, the agent (e.g., a vaccine composition, an agent that reduces methane production in a subject) can be coated with or disposed in a selected material to protect it from natural conditions which may detrimentally affect its ability to perform its intended function. The agent may be administered alone, or in conjunction with a pharmaceutically acceptable carrier or adjuvant. The agent (e.g., a vaccine composition, an agent that reduces methane production in a subject) also may be administered as a prodrug, which is converted to its active form in vivo. The term “conjoint” or “combination” administration, as used herein, refers to the administration of two or more agents that aid in reducing methane production in a subject. The different agents comprising the combination may be administered concomitant with, prior to, or following the administration of one or more agents. The term “fragment,” as used herein encompasses any and all that is less than the full length. In some embodiments, a fragment of a polypeptide of the present disclosure is an antigenic fragment of the polypeptide. Such antigenic fragment may comprise at least one epitope that binds to the antibody. In preferred embodiments, a fragment of a polypeptide of the present disclosure is a fragment of the polypeptide that is effective in eliciting immune response and / or inducing antibody production when administered to a subject. The term “methanogen,” as used herein, refers to a microorganism that produces methane as a metabolic byproduct. Methanogens belong to the domain Archaea, and include, but are not limited to those of a family Methanobacteriaceae, e.g., those of genera Methanobrevibacter, Methanosphaera, Methanomicrobium, Methanobacterium, Methanocorpusulum, Methanosaeta, Methanoculleus, Methanosarcina, and Thermoplasmatales. Specific methanogens include, but are not limited to, Methanobrevibacter ruminantium (e.g., the Ml strain or strain DSM 1093 (see e.g., World Wide Web at dsmz.de / microorganisms / html / strains / strain.dsm001093. htm) and Methanobrevibacter gottschalkii. Additional relevant species are further described below. The term “ruminant” refers to a hoofed herbivorous grazing or browsing mammal that is able to acquire nutrients from plant-based food by fermenting it in a specialized stomach prior to digestion, principally through microbial actions. The process, which takes place in the front part of the digestive system and therefore is called foregut fermentation, typically requires the fermented ingesta (known as cud) to be regurgitated and chewed again. The roughly 200 species of ruminants include both domestic and wild species. Ruminants include, but are not limited to, cattle (e.g., large domesticated ruminant animals, e.g., cows (including dairy cattle), bulls), all domesticated and wild bovines (i.e., those belonged to the family Bovidae; e.g., cows, cattle, bulls, bisons, yaks, African buffalos, water buffalos, antelopes), goats, sheep, giraffes, deer, caribou, and gazelles. In preferred embodiments, ruminants are domesticated. As used herein, the term “ruminant” includes ruminant-like animals or pseudo-ruminant animals such as macropods, llamas, camels, and alpacas. In some embodiments, a ruminant has not been administered with an agent that reduces methane. In other embodiments, a ruminant has been administered or is being administered with an agent that reduces methane. As used herein, the term “valency” refers to the number of antigenic components in the vaccine or polypeptide. In some embodiments, the vaccines are monovalent. In some embodiments, the vaccines are divalent. In some embedments the vaccines are trivalent. In some embodiments the vaccines are multi-valent. Multivalent vaccines may comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12,13,14, 15, 16, 17, 18, 19, 20, or more antigens or antigenic moieties (e.g., antigenic peptides, etc.). The antigenic components of the vaccines may be in a single polypeptide or peptide molecule. The antigenic components of the vaccines may be in separate polypeptide or peptide molecules. The term “subject” refers to any healthy or diseased animal, including any mammal, ruminant, canine, feline, or human. METHANOGENS The diversity of the ruminal methanogens is much smaller, and their diversity is much lower than that of rumen bacteria, with archaeal SSU rRNA only accounting for 6.8% of rumen total SSU rRNA. Archaea in the rumen is represented by <3.3% of the total rRNA (both 16S and 18S) therein. Representative family of methanogens includes Methanobacteriaceae. Rumen methanogens typically comprises 2-3% of the total microbial biomass in the rumen. Representative genera of methanogens include Methanobrevibacter, Methanosphaera, Methanomicrobium, Methanobacterium, Methanocorpusulum, Methanosaeta, Methanoculleus, Methanosarcina, and Thermoplasmatales. Certain species of ruminal methanogens have been isolated into pure cultures: Methanobacterium formicicum, Methanobacterium bryantii, Methanobrevibacter ruminantium, Methanobrevibacter gottschalkii, Methanobrevibacter millerae, Methanobrevibacter olleyae, Methanomicrobium mobile, Methanoculleus olentangyi, and Methanosarcina barkeri. Additional species have been recently isolated, including Methanobrevibacter boviskoreani (isolated from the rumen of Korean native cattle), Methanobacterium beijingense (isolated from the rumen of goat), Methanoculleus marisnigri (isolated from the rumen of Indian crossbred cattle), Methanoculleus bourgensis (isolated from the rumen of Holstein cattle), and Methanosarcina mazei (isolated from the rumen of Korean Hanwoo cattle) (based on the RDP database). A Thermoplasmatales-like pyrrolysine-dependent archaeon BRNA1 was also isolated from bovine (GenBank access number: CP002916). Collectively, 16S rRNA gene sequences from cultured methanogens only accounted for approximately 0.7% of the total archaeal sequences of rumen origin, and several taxa do not have a single cultured representative. Most of the isolates are members of the family Methanobacteriaceae. Compared to other anaerobic habitats where >100 species of methanogens of 28 genera have been isolated, the diversity and species richness of ruminal methanogens are quite low, reflecting the highly selective ruminal environment for methanogens. In addition, sequenced ruminal 16S rRNA gene clones shared >95% sequence similarity with that of Methanobrevibacter gottschalkii, Methanobrevibacter thaueri, Methanobrevibacter smithii and Methanosphaera stadtmanae, indicating that these species may be common ruminal methanogens. Much of the ruminal methanogen diversity was characterized by 16S rRNA gene sequences. The RDP Release 11 (Update 3) contains 8,623 archaeal 16S rRNA gene sequences of rumen origin. These sequences were generated using the Sanger sequencing technology, which produces higher sequence accuracy than NGS technologies, in 96 separate studies including 48 unpublished studies. About 90% of these sequences were assigned to methanogens. These sequences were classified to 10 known genera, with Methanobrevibacter being represented by 63.2% of all the sequences followed by Methanosphaera (9.8%), Methanomicrobium (7.7%), and Methanobacterium (1.2%). The order Thermoplasmatales, which was previously referred to as the rumen cluster C (RCC) group, is represented by 7.4% of the total archaeal sequences. CELL SURFACE PROTEINS OF METHANOGENS Provided herein is at least one cell surface protein or a fragment thereof (e.g., an antigenic fragment, e.g., a fragment comprising an epitope, e.g., a fragment comprising an extracellular domain or a portion thereof) of at least one methanogen that can be used in a vaccine composition, which can elicit immune response, antibody production, and antibody-mediated neutralization of the growth of methanogens and / or production of methane. Further provided herein are nucleic acid(s) encoding the at least one cell surface protein or a fragment thereof. In certain aspects, the at least one cell surface protein or a fragment thereof (e.g., an antigenic fragment, e.g., a fragment comprising an epitope, e.g., a fragment comprising an extracellular domain or a portion thereof) of at least one methanogen is of a family Methanobacteriaceae. In some embodiments, the at least one methanogen is of a genus selected from: Methanobrevibacter, Methanosphaera, Methanomicrobium, Methanobacterium, Methanocorpusulum, Methanosaeta, Methanoculleus, Methanosarcina, and Thermoplasmatales. In some embodiments, the at least one methanogen comprises Methanobacterium formicicum, Methanobacterium bryantii, Methanobrevibacter ruminantium, Methanobrevibacter millerae, Methanobrevibacter olleyae, Methanomicrobium mobile, Methanoculleus olentangyi, Methanosarcina barkeri, Methanobrevibacter boviskoreani, Methanobacterium beijingense, Methanoculleus marisnigri, Methanoculleus bourgensis, Methanosarcina mazei, Thermoplasmatales archaeon BRNA1, Methanobrevibacter gottschalkii, Methanobrevibacter thaueri, Methanobrevibacter smithii, Methanosphaera stadtmanae, Methanococcoides burtonii, Methanolobus psychrophilus RI5, Methanobacterium paludism, Methanohalobium evestigatum, Methanomethylovorans hollandica, Methanothrix soehngenii, Methanocaldococcus vulcanius, Methanosalsum zhilinae, Methanocorpusculum labreanum, Methanoregula formicica, Methanoculleus marisnigri, Methanocella arvoryzae, Methanoculleus bourgensis, Methanolacinia petrolearia, Methanospirillum hungatei, Methanoplanus limicola, Methanohalophilus mahii, Methanococcus aeolicus, Methanosphaerula palustris, Methanocaldococcus fervens, Methanocaldococcus jannaschii, Methanocaldococcus sp. FS406-22, Methanoregula boonei, Methanobrevibacter sp. AbM4, Methanobrevibacter ruminantium, Methanosphaera, Methanobacterium formicicum, Methanocaldococcus villosus, Methanosarcina barkeri, Methanobacterium lacus, Methanotorris igneus, Methanotorris formicicus, Methanocaldococcus infernus, Methanofollis liminatans, Methanothermococcus okinawensis, Methanobrevibacter smithii, Methanobrevibacter, Methanocella conradii, Methanothermococcus thermolithotrophicus, Methanococcus maripaludis, Methanococcus maripaludis, Methanococcus vannielii, Methanothermus fervidus, Methanosarcina acetivorans, Methanosarcina mazei, Methanosaeta harundinacea 6Ac, Methanococcus maripaludis, Methanococcus voltae, Methanolinea tarda, Methanolobus psychrophilus, Methanosaeta harundinacea, or any combination thereof. In some embodiments, the at least one methanogen comprises Methanobrevibacter ruminantium. In some embodiments, the at least one methanogen comprises Methanobrevibacter ruminantium Ml (DSM 1093). In preferrred embodiments, the at least one methanogen comprises Methanobrevibacter gottschalkii. In some embodiments, the at least one methanogen comprises Methanobrevibacter gottschalkii DSMI 1977. In some embodiments, a vaccine composition comprises a polypeptide or a fragment thereof (e.g., an antigenic fragment, an epitope) of at least one cell surface protein. In some embodiments, the polypeptide comprises the extracellular domain or a fragment thereof of at least one cell surface protein. In some embodiments, the polypeptide or a fragment thereof does not comprise the transmembrane and / or intracellular domains or a fragment thereof of the at least one cell surface protein. In certain aspects, provided herein are vaccine compositions comprising at least one cell surface protein or a fragment thereof (e.g., an antigenic peptide fragment, e.g., a peptide fragment comprising an epitope, e.g., a peptide fragment comprising an extracellular domain or a portion thereof, e.g., a polypeptide fragment, e.g., peptide fragment) of at least one methanogen. In some embodiments, a vaccine composition comprises at least one polypeptide and / or at least one peptide of at least one methanogen. In some embodiments, the at least one polypeptide or a fragment thereof does not comprise a signal peptide. In some embodiments, the at least one polypeptide or a fragment thereof does not comprise a transmembrane domain. In some embodiments, the at least one polypeptide or a fragment thereof comprises at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97% 98%, 99%, or 100% sequence identity to an amino acid sequence presented herein. In some embodiments, the at least one polypeptide or a fragment thereof comprises at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97% 98%, 99%, or 100% sequence identity to an amino acid sequence set forth in any one of Tables C-F, 1A, IB, 2A, 2B, 3 A, 3B, 4A, 4B, 5A, 5B, and 6A-6G, or a fragment thereof. In some embodiments, the at least one polypeptide or a fragment thereof comprises at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97% 98%, 99%, or 100% sequence identity to an amino acid sequence encoded by at least one nucleic acid presented herein. In some embodiments, the at least one polypeptide or a fragment thereof is encoded by a nucleic acid comprising the the nucleotide sequence set forth in any one of Tables C-F, 1A, IB, 2A, 2B, 3 A, 3B, 4A, 4B, 5A, 5B, and 6A-6G, or a fragment thereof. In some embodiments, the at least one polypeptide or a fragment thereof further comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 heterologous amino acid residues that are not native to the cell surface protein of a methanogen. In some embodiments, the at least one polypeptide or a fragment thereof further comprises about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 heterologous amino acid residues that are not native to the cell surface protein of a methanogen. In some embodiments, the at least one polypeptide or a fragment thereof further comprises no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 heterologous amino acid residues that are not native to the cell surface protein of a methanogen. In some embodiments, the heterologous amino acid residues comprise a heterologous signal peptide and / or a heterologous transmembrane domain. In some embodiments, a vaccine composition comprises at least one fragment (e.g., at least one polypeptide fragment and / or a peptide fragment) of at least one cell surface protein of at least one methanogen. In some embodiments, a vaccine composition comprises at least one fragment (e.g., polypeptide fragment and / or a peptide fragment), which is not a full-length cell surface protein of at least one methanogen. In some embodiments, the at least one fragment of at least one cell surface protein lacks at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 amino acid residues from its native full-length protein sequence. In some embodiments, the at least one fragment of at least one cell surface protein lacks about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 amino acid residues from its native full-length protein sequence. In some embodiments, the at least one fragment of at least one cell surface protein lacks no more than 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 amino acid residues from its native full-length protein sequence. In some embodiments, the at least one fragment of at least one cell surface protein lacks at least, about, or no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 amino acid residues from the N-terminus of its native full-length protein sequence. In some embodiments, the at least one fragment of at least one cell surface protein lacks at least, about, or no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 amino acid residues from the C-terminus of its native full-length protein sequence. In preferred embodiments, the at least one fragment of at least one cell surface protein comprises one or more extracellular domain or a portion thereof. A person of ordinary skill in the art can readily predict an extracellular portion of any given sequence by using a suitable tool known in the art, e.g., TMbed or TMHMM. In some embodiments, the at least one fragment of at least one cell surface protein lacks a native signal peptide. In some embodiments, the at least one fragment of at least one cell surface protein lacks a native transmembrane domain. In certain aspects, certain classes of methanogen cell surface proteins are particularly useful in generating an effective vaccine composition of the present disclosure (e.g., comprising at least one cell surface protein or a fragment thereof of at least one methanogen). In some embodiments, the at least one cell surface protein comprises at least one of the following structures and / or functions: adhesin-like, ATP-processing, cell wall biosynthesis, cofactor biosynthesis, CRISPR (provides methanogens an immunity against viruses), energy metabolism, enzyme, fatty acid synthesis, general metabolism, membrane protein, metalbinding, methanogenesis, methanogenesis Mtr proteins, methanogenesis MtrE proteins, phage related, proteolysis, transcription regulation, ribosomal, substrate binding, transcription, transport, and a protein whose gene expression changes in response to lauric acid stress (see Table 6G below). A person of ordinary skill in the art can determine the polypeptide sequences from the nucleic acid sequences, or determine the nucleic acid sequences from the polypeptide sequences presented herein or those known in the art. The nucleic acid and amino acid sequence information for nucleic acid and polypeptide molecules useful in the present invention are well-known in the art and readily available on publicly available databases, such as the National Center for Biotechnology Information (NCBI). The representative cell surface antigens of various methanogens and their nucleic acid sequences and amino acid sequences are provided in the US Application No. 18 / 350526 (e.g., Table 2A, Table 2B, Table 3, Table 17A, Table 19, Table 20, and Table 21), US Application No. 63 / 359,978, or US Application No. 63 / 524,513,, the entire contents of each of which are incorporated herein by reference in its entirety. Certain representative antigens and their amino acid and nucleic acid sequences are also presented in Tables C-F, 1 A, IB, 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, and 6A-6G of the present disclosure. SEQUENCES As used herein, coding region refers to regions of a nucleotide sequence comprising codons which are translated into amino acid residues, whereas noncoding region refers to regions of a nucleotide sequence that are not translated into amino acids (e.g., 5' and 3' untranslated regions). Complement [to] or complementary refers to the broad concept of sequence complementarity between regions of two nucleic acid strands or between two regions of the same nucleic acid strand. It is known that an adenine residue of a first nucleic acid region is capable of forming specific hydrogen bonds (base pairing) with a residue of a second nucleic acid region which is antiparallel to the first region if the residue is thymine or uracil. Similarly, it is known that a cytosine residue of a first nucleic acid strand is capable of base pairing with a residue of a second nucleic acid strand which is antiparallel to the first strand if the residue is guanine. A first region of a nucleic acid is complementary to a second region of the same or a different nucleic acid if, when the two regions are arranged in an antiparallel fashion, at least one nucleotide residue of the first region is capable of base pairing with a residue of the second region. In some embodiments, the first region comprises a first portion and the second region comprises a second portion, whereby, when the first and second portions are arranged in an antiparallel fashion, at least about 50%, and preferably at least about 75%, at least about 90%, or at least about 95% of the nucleotide residues of the first portion are capable of base pairing with nucleotide residues in the second portion. In other embodiments, all nucleotide residues of the first portion are capable of base pairing with nucleotide residues in the second portion. A nucleic acid is operably linked when it is placed into a functional relationship with another nucleic acid sequence. For instance, a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence. With respect to transcription regulatory sequences, operably linked means that the DNA sequences being linked are contiguous and, where necessary to join two protein coding regions, contiguous and in reading frame. For switch sequences, operably linked indicates that the sequences are capable of effecting switch recombination. There is a known and definite correspondence between the amino acid sequence of a particular protein and the nucleotide sequences that can code for the protein, as defined by the genetic code (shown below). Likewise, there is a known and definite correspondence between the nucleotide sequence of a particular nucleic acid and the amino acid sequence encoded by that nucleic acid, as defined by the genetic code. GENETIC CODE Alanine (Ala, A) GCA, GCC, GCG, GCT Arginine (Arg, R) AGA, ACG, CGA, CGC, CGG, CGT Asparagine (Asn, N) AAC, AAT Aspartic acid (Asp, D) GAC, GAT Cysteine (Cys, C) TGC, TGT Glutamic acid (Glu, E) GAA, GAG Glutamine (Gin, Q) CAA, CAG Glycine (Gly, G) GGA, GGC, GGG, GGT Histidine (His, H) CAC, CAT Isoleucine (He, I) ATA, ATC, ATT Leucine (Leu, L) CTA, CTC, CTG, CTT, TTA, TTG Lysine (Lys, K) AAA, AAG Methionine (Met, M) ATG Phenylalanine (Phe, FJ TTC, TTT Proline (Pro, P) CCA, CCC, CCG, CCT Serine (Ser, S) AGC, AGT, TCA, TCC, TCG, TCT Threonine (Thr, T) ACA, ACC, ACG, ACT Tryptophan (Trp, W) TGG Tyrosine (Tyr, Y) TAC, TAT Valine (Vai, V) GTA, GTC, GTG, GTT Termination signal (end) TAA, TAG, TGA An important and well-known feature of the genetic code is its redundancy, whereby, for most of the amino acids used to make proteins, more than one coding nucleotide triplet may be employed (illustrated above). Therefore, a number of different nucleotide sequences may code for a given amino acid sequence. Such nucleotide sequences are considered functionally equivalent since they result in the production of the same amino acid sequence in all organisms (although certain organisms may translate some sequences more efficiently than they do others). Moreover, occasionally, a methylated variant of a purine or pyrimidine may be found in a given nucleotide sequence. Such methylations do not affect the coding relationship between the trinucleotide codon and the corresponding amino acid. In making the changes in the amino sequences of polypeptide, the hydropathic index of amino acids may be considered. The importance of the hydropathic amino acid index in conferring interactive biologic function on a protein is generally understood in the art. It is accepted that the relative hydropathic character of the amino acid contributes to the secondary structure of the resultant protein, which in turn defines the interaction of the protein with other molecules, for example, enzymes, substrates, receptors, DNA, antibodies, antigens, and the like. Each amino acid has been assigned a hydropathic index on the basis of their hydrophobicity and charge characteristics these are: isoleucine (+4.5); valine (+4.2); leucine (+3.8); phenylalanine (+2.8); cysteine / cystine (+2.5); methionine (+1.9); alanine (+1.8); glycine (-0.4); threonine (0.7); serine (-0.8); tryptophane (-0.9); tyrosine (-1.3); proline (-1.6); histidine (-3.2); glutamate (3.5); glutamine (-3.5); aspartate (<RTI 3.5); asparagine (-3.5); lysine (-3.9); and arginine (-4.5). It is known in the art that certain amino acids may be substituted by other amino acids having a similar hydropathic index or score and still result in a protein with similar biological activity, i.e. still obtain a biological functionally equivalent protein. As outlined above, amino acid substitutions are generally therefore based on the relative similarity of the amino acid side-chain substituents, for example, their hydrophobicity, hydrophilicity, charge, size, and the like. Exemplary substitutions which take various of the foregoing characteristics into consideration are well-known to those of skill in the art and include: arginine and lysine; glutamate and aspartate; serine and threonine; glutamine and asparagine; and valine, leucine and isoleucine. In view of the foregoing, the nucleotide sequence of a DNA or RNA encoding a cell surface antigen nucleic acid (or any portion thereof) can be used to derive the polypeptide amino acid sequence, using the genetic code to translate the DNA or RNA into an amino acid sequence. Likewise, for polypeptide amino acid sequences, corresponding nucleotide sequences that can encode the polypeptide can be deduced from the genetic code (which, because of its redundancy, will produce multiple nucleic acid sequences for any given amino acid sequence). Thus, description and / or disclosure herein of a nucleotide sequence which encodes a polypeptide should be considered to also include description and / or disclosure of the amino acid sequence encoded by the nucleotide sequence. Similarly, description and / or disclosure of a polypeptide amino acid sequence herein should be considered to also include description and / or disclosure of all possible nucleotide sequences that can encode the amino acid sequence. Table 1A: Representative Antigens (full-length proteins) of Methanobrevibacter gottschalkii Set 1 (amino acid sequences (SEQ ID NOS 71070-71706) and nucleic acid sequences (SEQ ID NOS 71707-72343)) Table IB: Representative Antigens (full-length proteins) of Methanobrevibacter gottschalkii Set 1 (codon-optimized nucleic acid sequences) Left column discloses SEQ ID NOS 72344-72980 and right column discloses SEQ ID NOS 72981-73617. Table 2A: Representative Antigens (full-length proteins) of Methanobrevibacter gottschalkii Set 2 (amino acid sequences (SEQ ID NOS 73618-73993) and nucleic acid sequences (SEQ ID NOS 73994-74369)) Table 2B: Representative Antigens (full-length proteins) of Methanobrevibacter gottschalkii Set 2 (codon-optimized nucleic acid sequences) Left column discloses SEQ ID NOS 74370-74745 and right column discloses SEQ ID NOS 74746-75121. Table 3A: Representative Antigens (full-length proteins) of Methanobrevibacter gottschalkii Set 3 (amino acid sequences (SEQ ID NOS 75122-75220) and nucleic acid sequences (SEQ ID NOS 75221-75319) Table 3B: Representative Antigens (full-length proteins) of Methanobrevibacter gottschalkii Set 3 (codon-optimized nucleic acid sequences) Left column discloses SEQ ID NOS 75320-75418 and right column discloses SEQ ID NOS 75419-75517. Table 4A: Representative Antigens (fragments) of Methanobrevibacter gottschalkii Set 4 (amino acid sequences (SEQ ID NOS 75518-76049) and nucleic acid sequences (SEQ ID NOS 76050-76581)) Table 4B: Representative Antigens (fragments) of Methanobrevibacter gottschalkii Set 4 (codon-optimized nucleic acid sequences) Left column discloses SEQ ID NOS 76582-77112 and right column discloses SEQ ID NOS 77113-77643. Table 5A: Representative Antigens (fragments) of Methanobrevibacter gottschalkii Set 5 (amino acid sequences (SEQ ID NOS 77644-77967) and nucleic acid sequences (SEQ ID NOS 77968-78291)) Table 5B: Representative Antigens (fragments) of Methanobrevibacter gottschalkii Set 5 (codon-optimized nucleic acid sequences) Left column discloses SEQ ID NOS 78292-78615 and right column discloses SEQ ID NOS 78616-78939. Table 6A: Representative Antigens (fragments) of Methanobrevibacter gottschalkii Set 6 (amino acid sequences (SEQ ID NOS 78940-79032) and nucleic acid sequences (SEQ ID NOS 79033-79125)) Table 6B: Representative Antigens (fragments) of Methanobrevibacter gottschalkii Set 6 (codon-optimized nucleic acid sequences) Left column discloses SEQ ID NOS 79126-79218 and right column discloses SEQ ID NOS 79219-79311. Table 6C: Representative sequences of the cell surface proteins of Methanobrevibacter ruminantium Ml (GenBank: CP001719.1) See SEQ ID NO. 1 to SEQ ID NO. 2217 for the native nucleic acid sequences. See SEQ ID NO. 2218 to SEQ ID NO. 4434 for the bovine codon-optimized nucleic acid sequences. See SEQ ID NO. 4435 to SEQ ID NO. 6651 for the aminio acid sequences. Table 6D: Representative sequences of the cell surface proteins of Methanobrevibacter gottschalkii See SEQ ID NO. 6652 to SEQ ID NO. 8451 for the native nucleic acid sequences. See SEQ ID NO. 8452 to SEQ ID NO. 10251 for the bovine codon-optimized nucleic acid sequences. See SEQ ID NO. 10252 to SEQ ID NO. 12051 for the aminio acid sequences. Table 6E: Representative mtrE sequences of methanogens See SEQ ID NO. 12100 to SEQ ID NO. 12147 for the nucleic acid sequences. See SEQ ID NO. 12052 to SEQ ID NO. 12099 for the aminio acid sequences. Table 6F: Genes and Bos taurus codon-optimized nucleic acid sequence of the genes Name Species Bos taurus optimized nucleic acid sequence (SEQ ID NO) WP_004031278.1 Methanobacterium formicicum SEQ ID NO: 16969 WP_012956721.1 Methanobrevibacter ruminantium SEQ ID NO: 16970 WP_019264904.1 Methanobrevibacter smithii SEQ ID NO: 16971 WP_016359091.1 Methanobrevibacter sp. AbM4 SEQ ID NO: 16972 WP_011033493.1 Methanosarcina mazei SEQ ID NO: 16973 mru0143 Methanobrevibacter ruminantium SEQ ID NO: 16974 mru0842 Methanobrevibacter ruminantium SEQ ID NO: 16975 mru2048 Methanobrevibacter ruminantium SEQ ID NO: 16976 mrul222 Methanobrevibacter ruminantium SEQ ID NO: 16977 mru2047 Methanobrevibacter ruminantium SEQ ID NO: 16978 *The vaccine compositions of the present disclosure may comprise a polypeptides or a fragment thereof encoded by any one of the nucleic acids above. Table 6G: Exemplary structural / functional groups of representative cell surface proteins This table contains SEQ ID NOs of amino acid sequences of proteins; or SEQ ID NOs of nucleic acid sequences that encode the proteins that belong to the indicated structural and / or functional groups. (1) Adhesin-like proteins (SEQ ID NOs) 4438 4449 4453 4454 4465 4472 4517 4518 4519 4520 4524 4751 4752 4760 4761 4765 4926 5137 5156 5160 5205 5329 5335 5395 5396 5403 5556 5563 5639 5642 5654 5848 5849 5856 5897 5929 6082 6083 6158 6230 6387 6486 6487 6491 6522 6555 10280 10281 10282 10336 10337 10540 10591 10613 10614 10616 10665 10671 10677 10697 10723 11594 11595 11596 11646 11902 16976 16977 16774 16777 16780 16793 16794 16795 16797 16799 16807 16808 16857 16861 16863 53219 53220 53221 53222 53223 53231 53232 53233 53234 53235 53250 53251 53252 53253 53254 53262 53263 53264 53265 53266 53274 53275 53276 53277 53278 53286 53287 53288 53289 53290 53298 53299 53300 53301 53302 53310 53311 53312 53313 53314 53322 53323 53324 53325 53326 53334 53335 53336 53337 53338 53346 53347 53348 53349 53350 53358 53359 53360 53361 53362 53371 53372 53373 53374 53375 53383 53384 53385 53386 53387 53395 53396 53397 53398 53399 53409 53410 53411 53412 53413 53421 53422 53423 53424 53425 53433 53434 53435 53436 53437 53445 53446 53447 53448 53449 53457 53458 53459 53460 53461 53477 53478 53479 53480 53481 53489 53490 53491 53492 53493 53501 53502 53503 53504 53505 53524 53525 53526 53527 53528 53536 53537 53538 53539 53540 53551 53552 53553 53554 53555 53563 53564 53571 53572 53573 53581 53582 53583 53584 53585 53599 53603 53604 53605 53606 53614 53615 53616 53617 53618 53626 53627 53628 53629 53630 53638 53639 53640 53641 53642 53657 53658 53659 53660 53661 4482 4498 4506 4510 4511 4513 4516 4577 4594 4618 4656 4679 4689 4747 4772 4850 4851 4852 4883 4884 4922 5208 5244 5257 5261 5272 5275 5276 5409 5410 5411 5412 5509 5510 5521 5679 5753 5774 5790 5808 5818 5819 5930 5931 5932 5938 5945 6036 6038 6403 6428 6475 6480 6481 6484 6485 6556 6566 6579 6610 6621 6628 10279 10341 10342 10357 10369 10514 10522 10539 10617 10618 10627 10637 10638 10639 10640 10731 10810 10935 11091 11311 11331 11528 11903 11904 11909 11961 11987 16974 16975 16784 16785 16786 16787 16789 16791 16792 16800 16801 16802 16803 16804 16805 16806 16864 16865 16868 16869 16871 16872 53218 53224 53225 53226 53227 53228 53229 53230 53236 53237 53238 53239 53240 53241 53242 53255 53256 53257 53258 53259 53260 53261 53267 53268 53269 53270 53271 53272 53273 53279 53280 53281 53282 53283 53284 53285 53291 53292 53293 53294 53295 53296 53297 53303 53304 53305 53306 53307 53308 53309 53315 53316 53317 53318 53319 53320 53321 53327 53328 53329 53330 53331 53332 53333 53339 53340 53341 53342 53343 53344 53345 53351 53352 53353 53354 53355 53356 53357 53363 53364 53365 53366 53367 53368 53370 53376 53377 53378 53379 53380 53381 53382 53388 53389 53390 53391 53392 53393 53394 53400 53401 53402 53403 53406 53407 53408 53414 53415 53416 53417 53418 53419 53420 53426 53427 53428 53429 53430 53431 53432 53438 53439 53440 53441 53442 53443 53444 53450 53451 53452 53453 53454 53455 53456 53462 53463 53464 53465 53466 53467 53468 53482 53483 53484 53485 53486 53487 53488 53494 53495 53496 53497 53498 53499 53500 53508 53509 53510 53511 53512 53522 53523 53529 53530 53531 53532 53533 53534 53535 53541 53542 53546 53547 53548 53549 53550 53556 53557 53558 53559 53560 53561 53562 53574 53575 53576 53577 53578 53579 53580 53586 53587 53594 53595 53596 53597 53598 53607 53608 53609 53610 53611 53612 53613 53619 53620 53621 53622 53623 53624 53625 53631 53632 53633 53634 53635 53636 53637 53643 53644 53645 53646 53647 53648 53649 53662 53663 53664 53665 53666 53667 53668 53669 53670 53671 53672 53673 53674 53675 53684 53685 53694 53695 53696 53697 53698 53699 53700 53701 53702 53703 53704 53705 53706 53707 53708 53709 53710 53711 53712 53713 53714 53715 53716 53717 53718 53719 53720 53721 53722 53723 53724 53725 53726 53727 53728 53729 53730 53731 53732 53733 53734 53735 53736 53737 53738 53739 53740 53741 53742 53743 53744 53745 53746 53747 53748 53749 53750 53751 53752 53753 53754 53755 53756 53757 53758 53759 53760 53761 53762 53763 53764 53765 53766 53767 53768 53769 53770 53771 53772 53773 53774 53775 53776 53777 53778 53779 53780 53781 53782 53783 53784 53785 53786 53787 53788 53789 53790 53791 53792 53793 53794 53796 53797 53798 53799 53800 53801 53802 53803 53804 53805 53806 53807 53808 53809 53810 53811 53812 53813 53820 53821 53822 53823 53824 53825 53826 53827 53828 53829 53830 53831 53832 53833 53834 53835 53836 53837 53838 53839 53840 53841 53842 53843 53844 53845 53846 53847 53848 53849 53850 53851 53852 53853 53854 53855 53856 53857 53858 53859 53860 53861 53862 53866 53867 53868 53869 53870 53871 53872 53873 53874 53875 53876 53877 53878 53879 53880 53906 53907 53908 53909 53910 53911 53916 53917 53918 53919 53920 53921 53922 53923 53924 53925 53926 53927 53928 53929 53930 53931 53932 53934 53935 53936 53937 53938 53939 53940 53941 53942 53943 53944 53945 53946 53947 53948 53949 53950 53951 53952 53953 53954 53955 53956 53957 53958 53959 53960 53961 53962 53963 53964 53965 53966 53967 53968 53969 53970 53972 53973 53974 53976 53977 53978 53979 53980 53981 53982 53983 53984 53986 53987 53988 53989 53990 54010 54011 54034 54035 54036 54037 54038 54039 54040 54041 54042 54043 54044 54045 54046 54047 54048 54049 54050 54051 54052 54053 54054 54055 54056 54057 54058 54059 54060 54061 54062 54063 54064 54065 54066 54067 54068 54069 54070 54071 54072 54075 54076 54077 54078 54079 54081 54082 54093 54099 54100 54110 54111 54112 54113 54114 54115 54116 54117 54118 54122 54132 54133 54134 54135 54136 54137 54138 54139 54140 54149 54150 54151 54152 54155 54156 54188 54189 54190 54191 54192 54193 54194 54195 54196 54197 54198 54199 54200 54201 54202 54203 54204 54205 54222 54223 54224 54225 54242 54243 54247 54248 54249 54250 54251 54252 54253 54262 54263 54264 54265 54266 54267 54268 54269 54270 54271 54272 54283 54284 54285 54286 54287 54288 54289 54290 54291 54292 54293 54296 54297 54313 54314 54315 54316 54318 54328 54329 54330 54331 54332 54333 54334 54335 54336 54337 54353 54371 54372 54373 54374 54375 54376 54377 54378 54387 54392 54393 54417 54462 54463 54464 54465 54466 54467 54468 54469 54472 54473 54474 54475 54493 54494 54495 54496 54497 54498 54499 54500 54501 54502 54503 54504 54505 54506 54519 54520 54521 54526 54527 54542 54543 54544 54545 54646 54647 54648 54649 54650 54651 54652 54653 54654 54655 54656 54657 54699 54707 54708 54709 54710 54711 54712 54713 54716 54732 54733 54734 54735 54736 54737 54738 54739 54740 54748 54749 54750 54751 54755 54756 54757 54758 54773 54774 54775 54826 54827 54828 54829 54830 54831 54832 54833 54834 54835 54836 54837 54838 54854 54887 55009 55075 55076 55077 55078 55079 55080 55081 55082 55083 55084 55088 55089 55096 55097 55102 55103 55104 55105 55106 55114 55115 55116 55117 55118 55125 55126 55127 55128 55129 55130 55131 55142 55161 55162 55166 55167 55168 55169 55188 55189 55190 55191 55258 55259 55260 55261 55285 55286 55287 55288 55290 55291 55329 55370 55375 55376 55462 55463 55464 55465 55466 55467 55468 55469 55470 55471 55472 55473 55725 55726 55727 55732 55733 55797 55798 55799 55800 55805 55810 55811 55812 55813 55843 55844 55894 55895 55896 55897 55898 55899 55970 55971 56160 56161 56162 56163 56164 56165 56166 56180 56471 56472 56473 56552 56553 56554 56555 56591 56640 56641 56668 56669 56704 56705 56747 56748 56757 56758 56763 56764 56772 56773 56774 56775 56776 56777 56778 56779 57110 57111 57112 57144 57145 57153 57154 57181 57199 57200 57201 57202 57206 57221 57225 57250 57251 57252 57265 57266 57318 57319 57343 57344 57345 57375 57376 57381 57382 57383 57384 57407 57421 57422 57428 57429 57448 57449 57483 57484 57485 57486 57529 57530 57546 57619 57641 57642 57643 57644 57645 57689 57696 57697 57814 57815 57841 57842 57843 57844 57848 57922 58229 58230 58231 58232 58266 58267 58279 58280 58281 58282 58283 58284 58311 58312 58313 58314 58315 58351 58352 58353 58354 58355 58356 58357 58358 58578 58579 58703 58704 58705 58706 58707 58708 58709 58740 58741 58742 58743 58746 58747 58752 58761 58762 58768 58769 58841 58842 58940 58941 59909 59910 60356 60357 60445 60446 60468 60569 60663 60664 60676 60677 60751 60754 60755 60784 60785 60786 60787 60788 60789 60790 60791 60792 60814 60815 60940 60941 60942 60943 60944 60945 60946 60947 60997 60998 60999 61000 61001 61002 61006 61083 61093 61094 61095 61131 61136 61137 61138 61139 61140 61141 61142 61143 61162 61378 61379 61380 61492 61493 61494 61633 61679 61680 61681 61735 61736 61737 61738 61778 61779 61780 61911 61912 61913 61914 61915 61959 62019 62054 62055 62060 62061 62076 62077 62078 62079 62080 62081 62082 62083 62084 62103 62104 62107 62108 62137 62261 62262 62263 62270 62292 62293 62294 62295 62311 62332 62345 62384 62385 62540 62541 62542 62624 62625 62626 62627 62645 62646 62647 62648 62649 62650 62651 62652 62916 62917 62942 62957 63054 63066 63203 63204 63205 63206 63207 63211 63212 63213 63214 63215 63497 63551 63552 63553 63554 63555 63556 63557 63558 63632 63703 63706 63724 63735 63899 64177 64178 64179 64180 64181 64182 64183 64184 64200 64216 64252 64253 64254 64296 64297 64298 64299 64314 64337 64338 64339 64340 64341 64342 64343 64390 64471 64515 64516 64517 64528 64529 64535 64536 64537 64569 64570 64633 64634 64635 64636 64715 64716 64723 64724 64732 64733 64734 64739 64740 64741 64742 64755 64756 64776 64777 64778 64779 64780 64952 64953 64985 65050 65051 65127 65170 65320 65323 65506 65507 65508 65509 65510 65523 65531 65571 65586 65618 65642 65643 65664 65736 65810 65811 65812 65833 65948 65949 65950 65951 65952 66006 66144 66145 66393 66394 66396 66438 66439 66458 66538 66656 66670 66687 66716 66839 66892 66907 66908 66909 66952 67160 67161 67221 67281 67520 67774 67775 67776 67880 67924 68140 68141 68284 68402 68409 68421 68436 68476 68482 68571 68648 68649 68650 68690 68695 68698 68722 68723 68741 68742 68743 68744 68911 68989 69071 69116 69124 69160 69161 69162 69201 69202 69203 69204 69233 69278 69299 69300 69301 69333 69343 69344 69425 69464 69508 69523 69524 69574 69577 69585 69603 69613 69734 69839 69896 69897 69958 70062 70078 70081 70107 70114 70142 70143 70145 70154 70162 70204 70214 70231 70241 70249 70256 70289 70316 70320 70326 70334 70370 70402 70444 70446 70475 70500 70509 70511 70519 70521 70524 70537 70538 70539 70543 70546 70548 70558 70559 70569 70576 70585 70586 70587 70590 70591 70599 70601 70603 70613 70614 70616 70617 70619 70625 70631 70646 70648 70649 70658 70659 70666 70667 70668 70669 70677 70679 70692 70693 70696 70707 70731 70737 70741 70752 70757 70768 70796 70807 70808 70811 70819 70820 70821 70829 70837 70841 70843 70851 70852 70860 70865 70879 70880 70881 70882 70890 70891 70895 70896 70905 70906 70907 70918 70920 70926 70931 70951 70993 71009 71014 71015 71017 71020 71022 71031 71035 71038 71055 71062 71082 71083 71085 71104 71105 71106 71107 71116 71121 71182 71186 71195 71196 71214 71217 71218 71219 71220 71221 71226 71232 71233 71234 71235 71248 71251 71253 71255 71262 71265 71300 71343 71383 71461 71470 71531 71560 71561 71562 71580 71653 71654 71655 71658 71674 71682 75524 75525 75527 75544 75545 75546 75547 75548 75549 75550 75551 75552 75553 75554 75555 75566 75571 75572 75615 75620 75626 75627 75637 75638 75639 75640 75641 75642 75643 75644 75645 75646 75654 75658 75659 75660 75661 75679 75681 75682 75683 75695 75698 75725 75726 75727 75728 75729 75730 75731 75766 75798 75852 75858 75859 75860 75861 75862 75863 75864 75865 75866 75867 75868 75869 75870 75871 75914 75937 75938 75939 75948 76002 76003 76004 76006 76019 76020 76021 76022 76023 76024 76025 76026 76030 (2) ATP-processing proteins (SEQ ID NOs) 5132 5619 6156 6234 6293 6369 10378 10839 10840 11388 11452 53881 53882 53883 53884 53933 53991 53992 53993 53994 53995 54005 54006 54007 54008 54009 54073 54074 54172 54173 54174 54212 54213 54238 54239 54277 54278 54279 54280 54281 54282 54294 54295 54298 54299 54302 54303 54306 54320 54321 54324 54325 54369 54370 54388 54389 54390 54391 54394 54395 54396 54397 54398 54399 54400 54401 54402 54403 54404 54405 54406 54407 54408 54409 54410 54411 54412 54413 54414 54415 54416 54418 54419 54420 54421 54422 54423 54424 54425 54426 54427 54428 54429 54430 54431 54440 54442 54443 54536 54537 54844 54845 55542 55559 55560 55561 55562 55567 55577 55615 55616 55705 55724 55791 55793 55795 55796 55804 55806 55807 55809 56212 56213 56585 56586 56725 56726 57045 57046 57196 57207 57208 57363 57364 58862 58970 59114 59115 60701 61682 61994 61997 61998 61999 62000 62001 62002 62003 62008 62009 62010 62014 62015 62016 62017 62018 62022 62117 62279 62280 62281 62282 62308 62318 62333 62614 62615 62616 62617 63506 66812 66813 66814 67056 67761 68729 68731 69049 69050 69051 69081 69082 69168 69356 69595 69608 69614 69640 69659 69663 69665 69671 69715 69718 69726 69732 69735 69736 69741 69745 69747 69748 69781 69794 69960 70169 70180 70185 70350 70508 70609 70726 70761 70970 71047 71081 71095 71097 71125 71143 71149 71150 71210 71237 71245 71286 71305 71306 71309 71310 71386 71389 71394 71403 71409 71445 71457 71476 71493 71504 71505 71507 71508 71583 71584 71606 71608 71684 71686 71695 75573 75732 75733 75889 (3) Cell wall biosynthesis proteins (SEQ ID NOs) 16876 69386 69387 70804 (4) Cofactor biosynthesis proteins (SEQ ID NOs) 55348 55349 55350 56938 56939 56940 57423 57424 58518 58519 58520 58521 65125 68706 71029 (5) CRISPR proteins (provides methanogens an immunity against viruses) (SEQ ID NOs) 70636 71045 (6) Energy metabolism proteins (SEQ ID NOs) 58756 58757 61126 61127 61128 (7) Enzymes (SEQ ID NOs) 4617 4774 4986 6013 6559 11013 11468 11485 11506 11773 11845 16771 53045 53046 53047 53048 53049 53050 53051 53052 53053 53054 53055 53056 53057 53058 53059 53060 53061 53062 53063 53064 53065 53066 53067 53068 53069 53070 53071 53072 53073 53074 53075 53076 53077 53078 53079 53080 53081 53082 53083 53084 53085 53086 53087 53088 53089 53090 53091 53092 53093 53094 53095 53096 53097 53098 53099 53100 53101 53102 53103 53104 53105 53106 53107 53108 53109 53110 53111 53112 53113 53114 53115 53116 53117 53118 53119 53120 53121 53122 53123 53124 53125 53126 53127 53128 53129 53130 53131 53132 53133 53134 53135 53136 53137 53138 53139 53140 53141 53142 53143 53144 53145 53146 53147 53148 53149 53150 53151 53152 53153 53154 53155 53156 53157 53158 53159 53160 53161 53162 53163 53164 53165 53166 53167 53168 53169 53170 53171 53172 53173 53174 53175 53176 53177 53178 53179 53180 53181 53182 53183 53184 53185 53186 53187 53188 53189 53190 53191 53192 53193 53194 53195 53196 53197 53198 53199 53200 53201 53202 53203 53204 53205 53206 53207 53208 53209 53210 53211 53212 53213 53214 53215 53216 53217 53243 53244 53245 53246 53247 53248 53249 53404 54379 54380 54441 54517 54518 54798 54799 54800 54801 54807 54808 54809 54810 55017 55018 55019 55257 55434 55694 55714 55738 55767 55772 55781 55782 55792 55794 55808 56331 56332 56333 56606 56734 56735 56744 56745 56746 57077 57078 57120 57121 57122 57173 57174 57175 57176 57182 57183 57184 57332 57333 57430 57431 57432 57433 57434 57439 57440 57560 57561 57599 57600 57822 57823 57870 57871 58169 58170 58316 58436 58437 58438 58439 58588 58712 58713 58714 58720 58721 58729 58730 58731 58855 58893 58894 58901 58902 58909 58910 58959 58960 59122 59123 59124 59958 59959 59960 60337 60338 60339 60361 60362 60363 60364 60507 60508 60509 60510 60511 60512 60629 60630 60631 60632 60633 60641 60642 60643 60644 60645 60646 60647 60648 60649 60650 60651 60652 60653 60654 60655 60656 60657 60658 60675 60717 60718 60719 60763 60764 60765 60766 60896 60897 60898 61029 61030 61201 61202 61203 61204 61205 61206 61207 61208 61256 61257 61258 61259 61284 61285 61286 61287 61288 61289 61295 61383 61384 61385 61386 61387 61388 61389 61390 61391 61392 61393 61394 61395 61396 61397 61398 61399 61400 61401 61402 61403 61404 61409 61410 61411 61412 61413 61414 61417 61418 61419 61420 61421 61422 61423 61424 61425 61426 61427 61428 61429 61430 61431 61432 61433 61434 61435 61436 61437 61438 61439 61440 61444 61445 61446 61447 61448 61449 61709 61710 61711 61752 61753 61754 61830 61831 61832 61855 61856 61924 62056 62057 62085 62089 62099 62110 62133 62148 62208 62209 62210 62211 62212 62228 62389 62390 62391 62392 62393 62394 62395 62396 62405 62406 62420 62421 62422 62463 62464 62465 62481 62482 62483 62484 62493 62494 62495 62496 62497 62498 62499 62509 62510 62511 62512 62513 62514 62518 62519 62520 62521 62522 62523 62524 62525 62526 62527 62535 62536 62537 62547 62548 62549 62557 62558 62559 62565 62566 62567 62571 62572 62573 62574 62575 62576 62577 62578 62579 62590 62591 62641 62642 23 62673 62674 62675 62676 62677 63385 63502 63564 63565 63965 64067 64278 64563 64589 64604 64605 64606 64607 64608 64626 64627 64628 64629 64637 64651 64660 64679 64682 64687 64688 64693 64750 64784 64785 64786 64920 64921 65076 65237 65449 65479 65480 65481 65499 65532 65537 65589 65740 65775 65776 65992 65993 65994 65995 65996 65997 65998 66200 66201 66202 66203 66204 66205 66206 66207 66208 66229 66230 66231 66359 66477 66523 66536 66561 67804 67884 67885 67886 67910 67911 68392 68393 68394 68395 68396 68412 68413 68414 68661 68662 68664 68665 68701 68702 68719 68720 68762 68763 68825 68843 69060 69061 69167 69210 69217 69367 69368 69369 69398 69422 69423 69514 69556 69570 69600 69616 69617 69618 69623 69638 69639 69677 69708 69723 69956 69972 70038 70128 70171 70194 70284 70317 70318 70351 70354 70412 70413 70421 70466 70608 70633 70650 70651 70685 70686 70714 70733 70748 70758 70765 70925 71026 71036 71046 71058 71432 71078 71094 71117 71119 71131 71167 71177 71187 71193 71197 71200 71205 71207 71212 71215 71229 71230 71246 71250 71254 71258 71284 71293 71296 71331 71333 71339 71347 71350 71356 71373 71375 71376 71378 71379 71385 71410 71417 71431 71432 71434 71435 71444 71447 71448 71451 71458 71477 71509 71517 71526 71530 71538 71539 71556 71566 71567 71587 71602 71603 71609 71611 71623 71624 71625 71629 71635 71637 71639 71642 71643 71644 71656 71678 71702 71703 75778 75779 75780 75781 75782 75783 75784 75897 75998 (8) Fatty acid synthesis (SEQ ID NOs) 68659 68660 (9) General metabolism (SEQ ID NOs) 75905 75906 75907 75908 75909 75910 75985 5480 5955 11908 16866 16867 16874 53369 53405 54450 54451 54452 54453 54454 54888 54889 54890 54891 54892 55649 56541 56542 56550 56551 56556 56557 56558 56559 56560 56561 56562 56563 56749 56750 56759 56760 56761 56762 56801 56802 56826 56827 57308 57309 57902 57903 58386 58387 58388 58389 58413 58414 58415 58416 61231 61232 61233 62215 62216 62217 62223 62224 62963 63030 63031 63582 63916 63917 63918 63919 63920 63972 63973 63974 64450 64451 65272 65273 65539 65722 65723 65724 65766 65767 65786 66530 66616 66655 67200 67201 67253 67934 67946 67947 68134 68135 68306 68434 68435 68669 68670 68673 68682 68683 68709 68759 68784 68787 68840 68841 69175 69176 69226 69586 69591 69664 69672 69690 70033 70295 70310 70381 70485 70486 70610 70675 70921 71103 71136 71168 71192 71202 71324 71328 71341 71374 71388 71405 71419 71688 71691 76005 (10) Membrane proteins (SEQ ID NOs) 71422 71466 71471 71485 71573 71613 71657 4452 4478 4481 4483 4500 4505 4515 4529 4547 4580 4581 4584 4601 4606 4621 4627 4630 4657 4658 4659 4664 4665 4667 4668 4671 4682 4712 4713 4740 4749 4762 4764 4790 4791 4795 4809 4810 4811 4812 4842 4845 4848 4857 4861 4866 4879 4893 4903 4921 4923 4924 4928 4932 4942 4943 4945 4948 4954 4957 4975 4976 4978 4980 5000 5014 5029 5030 5031 5035 5037 5047 5055 5058 5064 5067 5072 5096 5103 5104 5116 5119 5126 5127 5139 5149 5150 5151 5153 5159 5169 5178 5179 5180 5188 5192 5193 5202 5235 5238 5264 5265 5266 5271 5273 5310 5334 5363 5373 5397 5400 5401 5408 5422 5433 5454 5455 5460 5463 5474 5487 5492 5513 5517 5529 5534 5549 5557 5576 5624 5626 5627 5628 5638 5645 5651 5664 5665 5666 5721 5734 5754 5762 5763 5768 5775 5807 5817 5855 5874 5883 5912 5925 5966 5967 5974 5982 5987 6010 6017 6030 6037 6039 6067 6068 6073 6074 6085 6086 6089 6125 6126 6170 6191 6217 6226 6227 6235 6264 6265 6266 6290 6314 6316 6321 6324 6332 6378 6382 6384 6401 6422 6423 6447 6455 6476 6482 6488 6489 6497 6538 6540 6550 6562 6568 6575 6578 6588 6604 6607 6612 6616 6617 6634 10272 10291 10306 10322 10325 10329 10347 10349 10350 10353 10368 10373 10383 10385 10391 10392 10408 10432 10438 10439 10443 10460 10462 10465 10497 10501 10502 10503 10504 10510 10512 10513 10515 10517 10538 10543 10545 10559 10564 10573 10586 10626 10641 10653 10667 10703 10721 10727 10734 10735 10736 10743 10744 10745 10752 10770 10792 10793 10797 10799 10848 10939 10940 10941 10944 10945 10978 10983 10984 24 11021 11024 11041 11042 11056 11057 11115 11126 11137 11138 11146 11158 11165 11177 11183 11186 11199 11217 11218 11219 11233 11234 11238 11247 11248 11268 11272 11276 11277 11301 11305 11312 11322 11326 11338 11351 11357 11358 11365 11385 11410 11428 11432 11434 11457 11474 11475 11476 11482 11537 11561 11565 11597 11599 11600 11622 11623 11631 11636 11637 11639 11643 11647 11679 11682 11683 11685 11691 11692 11701 11703 11709 11724 11752 11753 11763 11766 11778 11779 11784 11803 11874 11914 11916 11931 11932 11935 11937 11944 11954 11962 11963 11967 11976 12005 12010 12020 12021 12031 12049 53513 53514 53515 53516 53517 53518 53519 53520 53521 53601 53602 53650 53651 53652 53653 53654 53655 53656 53676 53677 53678 53679 53680 53681 53682 53683 53686 53687 53688 53689 53690 53691 53692 53693 53795 53912 53913 53914 53915 53971 53975 54014 54015 54016 54017 54080 54083 54084 54085 54086 54087 54088 54089 54090 54091 54092 54101 54102 54103 54104 54105 54106 54107 54123 54124 54125 54126 54127 54128 54129 54130 54131 54305 54447 54448 54449 54470 54471 54491 54492 54625 54626 54627 54660 54661 54662 54677 54693 54694 54746 54747 54761 54762 54763 54764 54765 54766 54767 54768 54769 54770 54771 54772 54776 54781 54782 54783 54784 54879 54880 54881 55015 55016 55065 55074 55090 55100 55101 55110 55111 55112 55113 55119 55120 55121 55122 55123 55124 55133 55134 55135 55136 55137 55138 55139 55140 55141 55143 55144 55145 55146 55147 55148 55149 55150 55151 55152 55153 55154 55155 55156 55157 55158 55159 55160 55163 55164 55165 55170 55171 55172 55173 55175 55176 55177 55197 55198 55199 55200 55201 55202 55205 55206 55207 55208 55209 55210 55211 55212 55213 55214 55215 55216 55217 55218 55219 55220 55221 55222 55223 55224 55225 55226 55227 55228 55229 55230 55231 55232 55233 55235 55236 55237 55239 55240 55241 55242 55243 55244 55245 55246 55247 55248 55249 55250 55251 55252 55253 55254 55255 55256 55262 55263 55264 55265 55266 55267 55268 55269 55270 55271 55272 55273 55274 55275 55276 55277 55278 55280 55281 55282 55283 55284 55293 55294 55295 55297 55298 55299 55300 55301 55303 55304 55305 55309 55310 55312 55313 55314 55315 55316 55317 55318 55319 55320 55321 55322 55323 55324 55325 55326 55327 55328 55330 55331 55332 55333 55334 55335 55336 55337 55338 55339 55340 55341 55342 55343 55344 55345 55346 55347 55351 55352 55353 55354 55355 55362 55363 55364 55365 55366 55367 55368 55377 55378 55379 55380 55381 55382 55388 55391 55392 55393 55394 55395 55396 55397 55407 55408 55409 55412 55418 55419 55420 55422 55424 55425 55427 55428 55429 55430 55431 55432 55433 55435 55436 55437 55438 55439 55440 55441 55442 55443 55444 55451 55452 55453 55454 55455 55456 55457 55458 55460 55461 55474 55475 55476 55478 55479 55483 55484 55485 55492 55493 55496 55497 55505 55506 55507 55508 55509 55510 55511 55513 55514 55515 55516 55521 55522 55523 55524 55525 55529 55530 55531 55532 55533 55534 55535 55536 55538 55539 55540 55541 55543 55544 55545 55548 55549 55550 55551 55552 55553 55554 55555 55556 55557 55563 55564 55568 55569 55570 55571 55572 55573 55574 55575 55576 55578 55579 55580 55581 55582 55583 55584 55587 55588 55589 55593 55594 55595 55597 55598 55600 55601 55602 55603 55604 55605 55606 55607 55608 55609 55610 55611 55612 55613 55614 55617 55618 55619 55620 55621 55622 55623 55625 55626 55627 55628 55635 55639 55640 55641 55642 55643 55644 55645 55646 55647 55648 55652 55653 55656 55657 55658 55659 55660 55661 55662 55663 55664 55665 55666 55667 55668 55669 55670 55671 55672 55673 55674 55675 55676 55677 55678 55679 55680 55681 55682 55683 55684 55685 55686 55687 55691 55692 55693 55701 55702 55703 55704 55706 55707 55708 55709 55710 55739 55740 55741 55742 55743 55744 55745 55746 55747 55748 55749 55757 55758 55759 55783 55784 55830 55831 55832 55969 55986 55987 56001 56002 56003 56004 56005 56006 56007 56012 56013 56014 56015 56081 56082 56083 56107 56108 56109 56110 56111 56112 56130 56131 56132 56133 56134 56135 56136 56153 56154 56155 56156 56157 56170 56171 56172 56173 56184 56185 56186 56187 56188 56197 56198 56199 56206 56207 56208 56209 56210 56214 56215 56216 56217 56218 56221 56222 56223 56224 56225 56259 56260 56261 56262 56271 56272 56273 56274 56275 56276 56277 56280 56281 56282 56283 56284 56288 56289 56290 56295 56296 56297 56298 56299 56300 56301 56302 56303 56307 56308 56309 56310 56311 56312 56313 56314 56315 56316 56317 56326 56327 56328 56329 56330 56334 56335 56336 56337 56338 56339 56340 56341 56347 56348 56349 56350 56412 56413 56414 25 56419 56420 56421 56449 56450 56451 56452 56465 56466 56476 56477 56478 56486 56500 56501 56502 56504 56505 56506 56507 56525 56526 56527 56528 56564 56565 56566 56567 56568 56569 56570 56571 56576 56577 56587 56588 56593 56594 56595 56596 56597 56598 56601 56654 56655 56682 56684 56685 56686 56687 56688 56689 56690 56691 56698 56699 56710 56711 56724 56736 56737 56738 56739 56740 56751 56752 56753 56754 56768 56769 56770 56771 56780 56781 56806 56807 56808 56830 56831 56832 56848 56849 56850 56866 56867 56868 56903 56904 56905 56947 56948 56960 56961 56962 56963 56996 56997 56998 56999 57016 57017 57018 57032 57033 57034 57035 57053 57054 57055 57097 57098 57099 57100 57101 57102 57103 57104 57105 57106 57113 57114 57115 57116 57117 57118 57119 57123 57124 57125 57126 57127 57128 57129 57137 57138 57148 57149 57150 57151 57165 57166 57211 57212 57294 57295 57298 57299 57300 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68824 68826 68827 68828 68832 68834 68835 68836 68846 68847 68848 68851 68852 68853 68854 68855 68859 68860 68861 68862 68868 68869 68873 68880 68881 68882 68883 68884 68885 68886 68887 68890 68891 68892 68893 68894 68895 68896 68897 68900 68901 68902 68903 68905 68906 68907 68908 68909 68910 68912 68913 68914 68915 68917 68918 68920 68921 68922 68925 68926 68930 68931 68932 68933 68937 68940 68941 68943 68944 68945 68946 68952 68956 68967 68968 68970 68971 68975 68976 68979 68984 68987 68988 68992 68993 69005 69006 69012 69013 69014 69016 69022 69023 69025 69026 69027 69028 69029 69032 69038 69039 69042 69044 69045 69047 69052 69054 69055 69062 69063 69065 69066 69069 69070 69074 69075 69076 69077 69083 69084 69086 69087 69088 69089 69090 69093 69094 69096 69097 69098 69099 69105 69106 69115 69126 69133 69137 69138 69139 69143 69144 69146 69147 69148 69149 69150 69151 69153 69154 69155 69156 69157 69158 69159 69163 69164 69169 69170 69173 69174 69177 69178 69181 69186 69187 69188 69191 69192 69193 69194 69195 69196 69197 69205 69207 69209 69211 69213 69214 69216 69223 69224 69227 69228 69229 69230 69231 69232 69234 69235 69238 69239 69240 69243 69245 69246 69247 69248 69249 69250 69251 69252 69254 69255 69256 69257 69258 69259 69262 69263 69268 69269 69270 69271 69272 69273 69275 69276 69277 69279 69280 69281 69282 69284 69289 69291 69292 69293 69296 69298 69302 69306 69307 69315 69316 69317 69318 69319 69323 69327 69330 69331 69332 69336 69337 69341 69342 69345 69346 69347 69348 69351 69354 69355 69357 69358 69359 69363 69364 69365 69370 69372 69373 69374 69377 69378 69382 69385 69388 69390 69391 69393 69394 69395 69396 69397 69399 69401 69402 69403 69404 69405 69407 69408 69409 69410 69411 69412 69413 69414 69415 69416 69417 69418 69419 69420 69421 69426 69427 69428 69429 69431 69432 69433 69434 69435 69438 69442 69443 69444 69445 69448 30 69449 69461 69462 69463 69465 69468 69473 69474 69477 69478 69479 69480 69482 69483 69485 69492 69493 69495 69496 69503 69504 69509 69512 69513 69517 69518 69519 69520 69521 69526 69530 69531 69535 69536 69538 69539 69540 69543 69546 69547 69548 69549 69551 69552 69553 69554 69555 69560 69563 69564 69566 69568 69569 69571 69572 69573 69575 69578 69579 69580 69581 69587 69588 69589 69590 69592 69596 69597 69598 69599 69604 69605 69606 69607 69609 69611 69619 69620 69622 69624 69625 69626 69627 69628 69630 69631 69635 69636 69641 69643 69645 69646 69647 69648 69649 69651 69653 69657 69660 69661 69662 69666 69670 69673 69674 69675 69676 69680 69684 69685 69686 69687 69689 69691 69692 69693 69694 69697 69698 69699 69700 69701 69702 69703 69704 69706 69710 69711 69713 69714 69716 69717 69720 69721 69724 69725 69727 69728 69729 69730 69733 69737 69738 69742 69743 69746 69749 69750 69751 69753 69754 69755 69756 69757 69758 69759 69760 69762 69763 69764 69765 69766 69767 69768 69770 69771 69772 69774 69775 69776 69777 69782 69783 69784 69785 69786 69788 69789 69790 69793 69800 69801 69802 69806 69807 69808 69809 69811 69814 69815 69821 69824 69827 69833 69835 69837 69838 69841 69842 69844 69845 69848 69851 69852 69853 69855 69857 69858 69865 69866 69868 69869 69870 69871 69872 69873 69875 69879 69880 69881 69884 69887 69888 69890 69892 69894 69898 69900 69901 69904 69907 69908 69909 69911 69912 69914 69915 69916 69917 69919 69925 69926 69929 69931 69933 69937 69945 69946 69950 69952 69959 69985 69988 69989 69991 69992 69993 69994 69998 69999 70002 70003 70004 70005 70006 70009 70011 70012 70013 70014 70016 70017 70019 70023 70026 70027 70028 70029 70030 70032 70034 70036 70037 70042 70043 70045 70046 70047 70049 70051 70052 70054 70055 70057 70059 70061 70063 70064 70065 70072 70073 70075 70076 70079 70080 70083 70085 70086 70089 70090 70091 70092 70093 70094 70095 70096 70098 70099 70100 70102 70103 70105 70106 70108 70109 70110 70111 70113 70115 70116 70117 70118 70119 70122 70127 70129 70133 70134 70135 70138 70139 70141 70144 70147 70148 70149 70150 70151 70155 70159 70160 70161 70163 70165 70170 70174 70176 70182 70187 70188 70191 70192 70195 70197 70198 70199 70200 70201 70202 70203 70205 70206 70207 70208 70209 70212 70213 70215 70216 70217 70219 70220 70221 70222 70223 70224 70225 70226 70229 70233 70234 70235 70236 70238 70239 70240 70243 70244 70245 70247 70248 70252 70254 70255 70257 70259 70260 70262 70264 70266 70267 70270 70271 70272 70273 70274 70275 70276 70277 70279 70280 70281 70282 70283 70286 70287 70290 70291 70292 70294 70296 70297 70298 70299 70300 70301 70303 70304 70307 70308 70311 70312 70313 70314 70315 70319 70321 70322 70328 70330 70331 70335 70337 70338 70342 70344 70345 70347 70348 70349 70352 70353 70356 70357 70358 70359 70360 70361 70363 70364 70365 70366 70367 70368 70369 70373 70374 70375 70376 70377 70378 70380 70382 70384 70385 70386 70387 70390 70391 70392 70393 70394 70396 70399 70400 70401 70409 70415 70416 70417 70422 70425 70429 70430 70436 70443 70450 70469 70473 70474 70476 70477 70479 70481 70483 70484 70488 70489 70492 70493 70494 70495 70498 70501 70504 70522 70526 70531 70536 70555 70562 70563 70564 70574 70577 70579 70580 70583 70593 70594 70605 70611 70618 70624 70630 70632 70638 70639 70640 70641 70642 70644 70647 70656 70660 70662 70663 70664 70665 70676 70678 70691 70701 70704 70708 70709 70712 70715 70717 70718 70719 70720 70722 70723 70727 70728 70729 70730 70732 70734 70738 70739 70740 70743 70744 70745 70746 70747 70749 70750 70751 70756 70759 70760 70762 70766 70767 70771 70772 70773 70774 70775 70776 70777 70779 70780 70781 70782 70783 70785 70786 70787 70788 70789 70790 70791 70792 70793 70794 70795 70797 70798 70799 70800 70802 70803 70805 70806 70809 70812 70813 70814 70815 70816 70818 70822 70824 70825 70827 70828 70833 70834 70835 70836 70838 70840 70844 70845 70846 70847 70848 70849 70853 70854 70855 70856 70857 70858 70859 70861 70862 70863 70864 70866 70867 70868 70869 70874 70875 70877 70878 70883 70884 70885 70886 70888 70889 70892 70897 70898 70899 70901 70902 70903 70904 70909 70910 70911 70912 70913 70915 70917 70919 70922 70923 70927 70930 70932 70934 70935 70937 70938 70939 70940 70941 70942 70943 70944 70946 70947 70949 70950 70952 70953 70955 70956 70957 70958 70960 70961 70962 70963 70964 70965 70966 70967 70968 70969 70971 70972 70975 70976 70977 70978 70979 70981 70982 70983 70984 70985 70986 70987 70988 70989 70990 70991 70995 70996 70998 70999 71000 71001 71002 71003 71004 71006 71007 71008 71010 71011 71013 71016 71019 71021 71023 71024 71027 71033 71042 71044 71051 71053 71056 71061 71064 71065 71066 71679 71070 71077 71088 71093 71096 71099 71109 71110 71111 71113 71120 71123 71128 71130 71132 71133 71140 71146 71147 71148 71151 71152 71154 71156 71157 71159 71160 71161 71163 71165 71166 71170 71173 71174 71175 71176 71179 71180 71181 71185 71194 71198 71199 71203 71204 71206 71213 71225 71236 71241 71257 71261 71263 71266 71267 71268 71271 71272 71273 71276 71280 71291 71292 71294 71295 71313 71344 71345 71346 71348 71349 71352 71354 71361 71362 71367 71368 71371 71372 71391 71396 71398 71399 71406 71408 71412 71415 71418 71421 71428 71429 71430 71438 71439 71442 71443 71449 71450 71453 71454 71459 71460 71462 71464 71467 71480 71482 71483 71486 71488 71489 71492 71495 71498 71500 71502 71512 71513 71514 71516 71534 71540 71542 71543 71544 71547 71548 71563 71564 71565 71569 71570 71572 71574 71575 71577 71578 71579 71588 71591 71592 71594 71595 71596 71597 71598 71600 71604 71617 71620 71621 71626 71627 71630 71631 71632 71636 71648 71662 71664 71667 71668 71669 71670 71672 71673 71675 71676 71677 71679 71689 71699 71700 71701 71705 71706 75529 75539 75540 75542 75543 75557 75561 75562 75570 75576 75577 75578 75582 75586 75587 75588 75589 75593 75594 75595 75596 75600 75611 75612 75613 75614 75616 75619 75629 75630 75631 75653 75669 75680 75690 75694 75699 75700 75705 75743 75767 75768 75772 75773 75774 75775 75776 75777 75787 75788 75807 75808 75812 75814 75816 75818 75819 75827 75828 75829 75830 75838 75839 75840 75841 75843 75844 75848 75849 75850 75851 75853 75880 75885 75886 75888 75891 75892 75893 75901 75902 75903 75904 75923 75924 75925 75926 75928 75940 75941 75943 75945 75946 75947 75957 75958 75960 75961 75962 75963 75964 75969 75970 75978 75979 75981 75982 75983 75984 75986 75987 75992 76011 76013 76015 76016 76018 76027 76028 76029 76033 76035 76044 76045 76046 76047 76048 71018 71057 71100 71145 71162 71183 71249 71285 71353 71404 71440 71472 71506 71551 71581 71618 71666 71692 75560 75592 75628 75706 75791 75837 75872 75917 75952 75980 76017 (11) Metal-binding proteins (SEQ ID NOs) 4825 4936 4973 5174 5220 5224 5382 6020 6050 6142 6317 6337 6605 10463 10856 10857 10862 10885 11032 11034 11431 11869 11994 16978 16769 16778 16779 16781 16782 16783 16858 16862 16873 16877 16879 16880 54097 54098 54143 54144 54145 54146 54147 54148 54153 54157 54158 54159 54160 54161 54162 54163 54164 54165 54166 54167 54169 54170 54171 54175 54176 54177 54178 54179 54180 54181 54182 54184 54185 54186 54187 54209 54210 54211 54214 54215 54216 54217 54219 54226 54227 54228 54229 54230 54231 54232 54233 54234 54235 54237 54240 54241 54244 54245 54246 54307 54308 54455 54456 54457 54459 54460 54511 54512 54513 54514 54665 54666 54667 54802 55005 55566 55630 55631 55632 55842 56663 56664 56700 56701 56702 56703 56732 56733 56815 56816 56828 56829 57141 57142 57143 57159 57160 57162 57213 57214 58180 58181 58262 58263 58264 58265 58268 58269 58271 58299 58300 58301 58302 58305 58306 58307 58308 58317 58318 58320 58394 58395 58396 58397 58458 58459 58460 58461 58544 58545 58547 59096 59097 59098 59099 59100 60610 60611 60612 60613 60614 61601 62043 62044 62045 62166 62167 62367 62368 62369 62370 62438 63121 63122 63179 63180 63277 63629 63630 63631 64185 64350 64351 65143 65188 65225 65324 65545 65559 65581 65582 65591 65592 65607 65829 65830 65841 65842 65848 65849 65850 65865 65918 65964 65983 66007 66008 66059 66060 66061 66062 66066 66075 66076 66077 66078 66092 66093 66094 66095 66097 66098 66177 66184 66386 66387 66532 66567 66646 66647 67110 67111 67212 67540 67586 67692 67950 67987 68510 68511 68535 68592 68593 68671 68672 69056 69057 69104 69182 69253 69265 69266 69267 69557 69558 69612 69632 69744 69797 69798 69944 69971 70020 70021 70041 70070 70104 70156 70346 70371 70427 70447 70448 70449 70451 70453 70455 70458 70459 70463 70465 70467 70470 70471 70487 70490 70491 70497 70506 70507 70510 70514 70530 70540 70554 70556 70557 70561 70626 70653 70873 71012 71054 71067 71086 71153 71320 71321 71325 71329 71332 71334 71357 71359 71364 6468 12018 16878 54154 54168 54183 54218 54236 54458 55480 56731 57161 58270 58319 58546 61600 63120 64352 65828 65984 66079 66560 68345 69183 69863 70442 70468 70535 71072 71365 71366 71420 71441 71456 71499 71601 71610 71622 71647 71685 71697 75590 75753 75754 (12) Methanogenesis 75755 75762 75785 75786 proteins (SEQ ID NOs) 75999 76000 76001 76042 5833 5835 5836 5837 5838 5839 5840 5841 5842 5843 5844 6360 6432 6436 6437 6438 6439 6440 6441 6442 6443 6444 6445 10474 10475 10476 10477 10478 10479 10480 10481 10482 10483 10484 10485 11511 11549 11554 11555 11556 11557 11558 11559 11560 11562 16859 54741 54742 54743 54744 54745 54786 54787 54788 54789 54790 54871 54872 54873 54874 54875 56843 56844 57209 57210 57215 57216 57217 57218 57219 57220 57230 57231 57232 57233 57234 57235 57267 57268 57269 57270 57271 57272 57273 57274 57275 57276 57277 57346 57347 57348 57349 57350 57351 57365 57366 57367 57368 57416 57417 57418 57461 57462 57463 57464 57499 57500 57501 57510 57511 57512 57706 57707 57708 57721 57722 57723 57734 57735 57736 57737 57738 57739 57979 57980 57981 57982 57983 57984 57998 57999 58000 58001 58002 58003 58011 58012 58013 58017 58018 58019 58023 58024 58025 58029 58030 58031 58035 58036 58037 58047 58048 58049 58065 58066 58067 58077 58078 58079 58080 58081 58082 58104 58105 58106 58107 58108 58109 58113 58114 58115 58119 58120 58121 58144 58145 58146 58185 58186 58187 58188 58189 58190 58191 58192 58193 58194 58195 58196 58200 58201 58202 58203 58204 58205 58206 58209 58210 58211 58212 58213 58214 58242 58243 58244 58245 58246 58843 58844 58845 58846 59842 59843 59844 59845 59846 59847 60615 60616 60617 60618 60624 60625 60626 60627 60628 60634 60635 60636 60637 60659 61096 61097 61098 61240 61241 61242 61243 61511 61531 61532 61533 61534 61712 61713 61714 61715 61790 61793 61796 61806 61833 61846 61851 61854 61857 61871 61874 61883 61888 61891 61925 61944 61945 61956 61962 62778 62779 63283 63284 63844 63845 63846 63851 63903 63911 63924 63925 63929 63932 63933 63935 63936 63937 63938 63939 63940 63941 63942 63943 63944 63945 63949 63951 63955 63956 63957 63958 63962 63966 63967 63968 63977 63981 63982 63983 63984 63985 63986 64041 64141 64165 65295 65303 65305 65310 65315 65316 65329 65334 65467 65469 65486 65503 65511 65517 65519 65530 65534 65538 65540 65546 65550 65656 65880 66628 67044 67561 67566 67568 67569 67571 67572 67575 67578 67580 67582 67669 67670 67682 67683 67694 67700 67711 67712 67718 67719 67720 67723 67724 67729 67732 67735 67738 67739 67742 67743 67754 67755 67756 67757 67783 67784 67789 67790 67795 67796 67802 67803 67805 67806 67809 67810 67811 67812 67821 67822 67823 67824 67831 67832 67841 67842 67845 67846 67863 68637 68712 68721 68732 68733 68734 68735 68736 68737 68739 68740 68748 68749 68751 68752 68755 68757 68758 68760 68761 68769 68856 68857 68871 68874 68878 68916 69112 69113 69114 69140 69145 69215 69244 69290 69297 69303 69310 69329 69335 69338 69350 69360 69361 69366 69389 69392 69406 69439 69455 69469 69475 69476 69481 69484 69489 69491 69494 69497 69498 69500 69501 69502 69505 69506 69525 69527 69534 69582 69920 69924 69934 69939 69940 69941 69942 69943 69948 69949 69951 69953 69954 69961 69962 69964 69967 69968 69970 69973 69974 69975 69977 69978 69979 69980 69981 69982 69983 69986 69987 69990 69995 69997 70022 70040 70048 70056 70068 70074 70097 70112 70124 70146 70153 70175 70193 70261 70309 70339 70343 70355 70389 70395 70408 70428 70452 70457 70464 70520 70523 70529 70534 70544 70547 70550 70553 70560 70565 70566 70573 70578 70581 70584 70588 70592 70595 70597 70598 70600 70606 70607 70670 70687 70689 70695 70697 70699 70702 70703 71336 71337 (13) Methanogenesis 70705 70706 70711 70713 71358 71527 75913 Mtr proteins (SEQ ID NOs) 70736 70769 70770 70870 70945 71358 6349 6350 6351 6352 6353 6354 11495 11496 11498 11499 11500 65965 66149 66150 66166 66173 66174 66948 67048 67049 67153 67192 67246 67443 67479 67480 67481 67486 67489 67495 67500 67512 67542 67601 68002 70323 70324 70332 70333 70397 70398 70671 70673 70680 70688 70690 70710 70980 71521 71282 71282 (14) Methanogenesis 71503 71518 71519 71520 MtrE proteins (SEQ ID NOs) 71521 71522 71523 71524 71651 75911 6355 11501 12052 12053 12054 12055 12056 12057 12058 12059 12060 12061 12062 12063 12064 12065 12066 12067 12068 12069 12070 12071 12072 12073 12074 12075 12076 12077 12078 12079 12080 12081 12082 12083 12084 12085 12086 12087 12088 12089 12090 12091 12092 12093 12094 12095 12096 12097 12098 12099 65294 16969 65312 16970 65962 16971 65963 16972 66049 16973 66091 64574 66635 65049 66636 65136 66808 65190 71525 65201 75912 65238 (15) Phage related (SEQ ID NOs) 4742 4744 4745 4750 57399 57400 57401 69072 (16) Proteolysis (SEQ ID NOs) 4466 4564 4672 4754 5032 5120 5314 5461 5560 5678 5695 5744 5936 6069 6109 6130 6600 10411 10525 10580 10737 11111 11232 11426 11638 11652 11798 16770 16788 16790 53469 53470 53471 53472 53473 53474 53475 53476 53506 53507 53814 53815 53816 53817 53818 53819 53863 53864 53865 53885 53886 53887 53888 53889 53890 53891 53892 53893 53894 53895 53896 53897 53898 53899 53900 53901 53902 53903 53904 53905 53996 53997 53998 53999 54000 54001 54002 54003 54004 54012 54013 54022 54023 54024 54025 54026 54027 54028 54029 54030 54031 54032 54033 54141 54254 54300 54301 54322 54323 55371 55372 55373 55374 55500 56158 56159 57152 57223 57224 57359 57410 57411 57412 57885 57886 57887 57888 57889 58584 58585 60294 60295 60296 60297 60690 60691 60692 60693 60773 60774 60775 60776 60777 60778 60779 60845 60874 61622 61623 61909 61910 61934 61976 61979 61982 61983 61990 62063 62064 62093 62105 62165 62175 62176 62183 62189 62190 62191 62192 62193 62196 62197 62202 62203 62204 62213 62214 62222 62227 62229 62230 62255 62256 62361 62362 62386 62433 62434 62436 62437 62444 62445 62446 62447 62944 62945 62946 63152 63153 63467 63950 64060 64061 64062 64063 64064 64065 64066 64204 64205 64206 64265 64270 64272 64273 64294 64295 64331 64332 64333 64379 64391 64392 64393 64403 64404 64405 64413 64414 64415 64427 64428 64429 64436 64437 64438 64452 64453 64454 64458 64459 64460 64473 64474 64475 64482 64483 64484 64488 64506 64511 64513 64520 64521 64522 64564 64591 64592 64593 64598 64599 64600 64620 64621 64622 64643 64644 64645 64646 64647 64648 64652 64653 64654 64667 64668 64669 64699 64700 64701 64720 64929 64930 64957 64958 64959 65012 65013 65014 65120 65121 65138 65139 65140 65277 65278 65283 65301 65302 65357 65358 65367 65368 65379 65380 65381 65382 65385 65386 65387 65388 65389 65390 65391 65406 65407 65408 65409 65418 65419 65424 65425 65426 65427 65429 65430 65437 65438 65444 65445 65450 65451 65453 65454 65455 65456 65457 65458 65459 65460 65470 65565 65788 65789 65790 65798 65799 65800 65813 65814 65815 65874 65891 65892 66033 66034 66038 66133 66161 66171 66172 66191 66212 66228 66239 66240 66264 66700 66886 66887 66888 67060 67061 67325 67326 67327 67531 67532 67666 67667 67705 67706 67707 67807 67808 67855 67856 67859 67860 67936 67995 68017 68018 68022 68023 68076 68077 68110 68111 68112 68113 68131 68132 68142 68143 68146 68147 68166 68167 68168 68169 68170 68171 68176 68177 68182 68183 68186 68187 68196 68197 68202 68203 68204 68205 68214 68215 68222 68223 68226 68227 68228 68229 68230 68231 68242 68243 68244 68245 68250 68251 68254 68255 68269 68270 68271 68272 68273 68274 68326 68327 68328 68329 68362 68373 68374 68418 68602 68628 68635 68636 68643 68675 69127 69128 69129 69179 69180 69199 69200 69236 69237 69328 69446 69447 69593 69787 69862 69882 69883 70035 70157 70184 70288 70340 70379 70383 70411 70461 70462 70533 70654 70655 70894 71084 71135 71142 71188 71211 71269 71390 71411 71437 71497 71576 71582 71634 75526 75584 75585 75621 75622 75623 75636 75701 75835 75836 75890 75990 75991 (17) Transcription regulation (SEQ ID NOs) 54777 54778 54779 54780 70620 (18) Ribosomal (SEQ ID NOs) 61896 61897 62721 66723 66724 66725 66726 66729 67400 71216 71355 71652 (19) Substrate binding (SEQ ID NOs) 16860 (20) Transcription (SEQ ID NOs) 57620 57621 59813 65150 65151 65152 68305 68658 69018 69019 69020 70177 70179 70285 70621 70622 71134 71231 71360 71427 71607 71646 (21) Transport (SEQ ID NOs) 4437 4442 4450 4451 4480 4503 4527 4550 4573 4574 4575 4632 4634 4635 4640 4641 4649 4650 4673 4685 4686 4699 4717 4763 4766 4786 4792 4800 4813 4839 4840 4841 4900 4915 4929 4930 4967 4970 4972 4974 4991 4992 5003 5004 5040 5042 5049 5069 5092 5093 5129 5130 5138 5157 5222 5241 5254 5260 5308 5316 5317 5318 5383 5419 5426 5435 5503 5514 5515 5516 5623 5633 5634 5653 5717 5757 5764 5765 5772 5802 5805 5815 5860 5869 5871 5888 5942 5954 5956 6029 6044 6048 6049 6059 6060 6090 6134 6140 6141 6145 6153 6154 6167 6183 6197 6208 6209 6218 6221 6272 6273 6312 6377 6385 6400 6416 6452 6456 6477 6478 6479 6483 6608 6609 6629 6638 6640 6650 10256 10271 10275 10276 10284 10295 10296 10302 10303 10343 10352 10354 10355 10365 10380 10381 10405 10406 10407 10409 10425 10496 10499 10516 10527 10528 10578 10623 10624 10625 10629 10630 10648 10651 10652 10655 10656 10657 10663 10701 10718 10728 10738 10753 10841 10842 10845 10847 10850 10851 10854 10855 10863 10864 10870 10905 10932 10976 11054 11073 11083 11095 11121 11124 11134 11140 11141 11142 11159 11205 11214 11215 11227 11274 11329 11341 11342 11343 11355 11371 11421 11433 11469 11470 11513 11514 11530 11544 11564 11572 11574 11575 11583 11626 11671 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64707 64708 64709 64710 64711 64714 64721 64722 64725 64726 64727 64728 64730 64735 64746 64747 64757 64758 64759 64761 64767 64781 64782 64788 64789 64790 64791 64792 64794 64795 64796 64797 64807 64808 64809 64810 64811 64812 64813 64814 64815 64816 64818 64819 64820 64821 64826 64827 64828 64830 64834 64835 64836 64837 64838 64839 64840 64841 64842 64843 64844 64845 64846 64847 64848 64849 64850 64851 64855 64856 64857 64858 64859 64860 64861 64862 64863 64864 64865 64869 64870 64871 64872 64873 64874 64875 64876 64877 64878 64879 64880 64881 64882 64883 64886 64887 64888 64889 64890 64891 64892 64893 64894 64895 64896 64897 64898 64899 64900 64904 64905 64906 64907 64908 64909 64910 64911 64914 64915 64916 64917 64918 64919 64922 64923 64924 64925 64926 64927 64928 64931 64932 64933 64934 64935 64939 64940 64941 64942 64943 64944 64945 64946 64947 64948 64949 64950 64951 64960 64961 64962 64963 64964 64965 64966 64967 64968 64971 64976 64977 64978 64983 64984 64986 64987 64989 64994 64995 64996 64997 65001 65005 65006 65007 65018 65019 65023 65027 65028 65029 65030 65031 65032 65033 65064 65065 65066 65067 65075 65082 65083 65084 65087 65088 65089 65090 65091 65092 65093 65094 65095 65096 65097 65098 65099 65101 65102 65103 65107 65113 65114 65115 65116 65117 65118 65119 65126 65128 65129 65130 65153 65160 65161 65167 65168 65169 65182 65183 65189 65210 65211 65212 65213 65222 65223 65224 65230 65235 65236 65243 65244 65245 65246 65247 65248 65249 65256 65257 65258 65262 65263 65264 65268 65269 65270 65271 65274 65275 65276 65291 65292 65293 65299 65300 65304 65306 65311 65319 65321 65322 65332 65333 65335 65369 65370 65371 65373 65375 65376 65392 65414 65417 65428 65441 65452 65464 65473 65474 65477 65478 65488 65489 65494 65495 65496 65497 65501 65502 65512 65513 65520 65521 65522 65535 65536 65547 65548 65552 65553 65554 65555 65560 65561 65562 65563 65568 65569 65570 65572 65573 65574 65575 65578 65579 65583 65584 65587 65588 65590 65593 65594 65595 65596 65597 65598 65599 65600 65601 65602 65603 65604 65605 65606 65608 65609 65610 65611 65614 65615 65616 65617 65619 65620 65621 65622 65623 65624 65625 65626 65630 65631 65632 65633 65640 65641 65644 65645 65659 65660 65665 65666 65667 65668 65669 65670 65671 65672 65673 65674 65675 65676 65677 65678 65679 65682 65683 65685 65686 65687 65688 65689 65690 65693 65694 65695 65696 65699 65700 65701 65702 65703 65704 65705 65706 65707 65708 65709 65712 65713 65714 65715 65717 65718 65725 65726 65727 65728 65729 65730 65731 65733 65734 65737 65739 65741 65744 65745 65746 65747 65748 65749 65750 65751 65752 65753 65756 65757 65758 65761 65762 65763 65765 65771 65773 65774 65777 65778 65779 65780 65781 65782 65783 65785 65803 65804 65805 65806 65819 65820 65824 65825 65826 65838 65839 65840 65851 65852 65853 65854 65855 65863 65864 65866 65867 65868 65869 65870 65871 65872 65873 65876 65877 65878 65879 65881 65882 65887 65893 65894 65896 65897 65898 65899 65900 65901 65902 65903 65904 65905 65906 65907 65908 65909 65910 65911 65912 65916 65924 65925 65926 65928 65929 65933 65934 65937 65940 65941 65942 65943 65947 65959 65960 65961 65967 65969 66001 66002 66013 66014 66015 66016 66022 66023 66024 66025 66026 66029 66030 66031 66032 66035 66036 66039 66040 66041 66042 66045 66046 66047 66048 66053 66054 66063 66064 66065 66067 66068 66069 66070 66071 66072 66073 66074 66080 66081 66082 66085 66089 66090 66099 66100 66101 66102 66115 66116 66120 66121 66138 66139 66142 66143 66146 66147 66153 66154 66167 66168 66175 66176 66178 66179 66180 66181 66186 66187 66189 66195 66196 66197 66198 66199 66209 66210 66213 66214 66215 66216 66217 66218 66219 66220 66221 66222 66223 66224 66234 66235 66241 66242 66244 66245 66248 66249 66250 66251 66252 66253 66254 66255 66256 66257 66258 66259 66265 66266 66268 66269 66270 66271 66272 66275 66276 66277 66278 66281 66282 66283 66287 66289 66290 66298 66299 66310 66314 66332 66370 66371 66389 66390 66391 66397 66398 66399 66401 66402 66405 66406 66407 66408 66409 66413 66426 66446 66448 66449 66450 66463 66464 66465 66473 66476 66480 66490 66491 66492 66493 66500 66501 66503 66504 66510 66511 66512 66514 66515 66518 66525 66531 66537 66539 66540 66545 66546 66548 66549 66551 66552 66553 66554 66558 66572 66573 66577 66578 66580 66581 66591 66611 66622 66623 66629 66630 66632 66633 66637 66638 66640 66641 66643 66644 66645 66648 66649 66650 66651 66653 66654 66660 66661 66662 66663 66664 66666 66667 66668 66669 66684 66685 66689 66690 66692 66693 66701 66708 66709 66718 66719 66736 66737 66744 66745 66746 66747 66753 66754 66758 66759 66762 66763 66766 66767 66768 66769 66770 66786 66787 66789 66790 66791 66794 66795 66796 66797 66798 66800 66801 66802 66803 66804 66805 66806 66807 66810 66811 66815 66816 66822 66823 66824 66825 66826 66827 66828 66829 66830 66831 66832 66833 66834 66835 66836 66843 66844 66845 66846 66847 66848 66852 66853 66857 66858 66860 66861 66862 66863 66864 66865 66866 66869 66870 66873 66874 66875 66876 66877 66878 66889 66890 66891 66901 66904 66905 66906 66910 66911 66914 66915 66916 66917 66918 66921 66928 66929 66931 66932 66933 66937 66938 66940 66944 66945 66950 66951 66960 66969 66970 66971 66973 66977 66981 66982 66985 66986 66987 66988 66989 66990 66999 67000 67001 67007 67008 67009 67010 67011 67012 67013 67014 67015 67016 67017 67020 67021 67022 67026 67027 67028 67039 67040 67041 67050 67051 67052 67053 67054 67055 67057 67058 67064 67065 67066 67067 67068 67069 67071 67072 67073 67074 67075 67076 67077 67078 67079 67080 67081 67082 67083 67084 67085 67086 67087 67088 67094 67095 67096 67097 67100 67101 67102 67103 67104 67105 67107 67108 67109 67113 67114 67115 67118 67119 67120 67123 67124 67125 67126 67127 67128 67129 67130 67131 67132 67133 67134 67135 67136 67137 67139 67140 67141 67148 67149 67151 67152 67157 67158 67163 67164 67171 67175 67176 67177 67189 67190 67208 67227 67228 67232 67233 67250 67255 67256 67259 67275 67276 67277 67278 67279 67280 67287 67288 67289 67291 67292 67293 67294 67295 67297 67298 67299 67300 67301 67303 67304 67308 67309 67310 67311 67312 67313 67314 67315 67316 67321 67322 67323 67324 67328 67329 67330 67331 67333 67334 67335 67336 67337 67338 67339 67341 67342 67343 67345 67346 67347 67348 67349 67350 67351 67352 67353 67354 67355 67356 67357 67358 67360 67361 67362 67363 67364 67367 67368 67369 67373 67374 67375 67376 67377 67378 67379 67380 67381 67383 67384 67385 67386 67387 67388 67389 67390 67391 67394 67395 67396 67401 67402 67403 67407 67408 67409 67411 67412 67413 67414 67415 67416 67418 67419 67420 67422 67423 67424 67425 67426 67427 67428 67429 67430 67432 67433 67434 67437 67438 67439 67440 67441 67442 67448 67449 67450 67452 67453 67454 67471 67475 67476 67487 67488 67496 67497 67498 67499 67503 67504 67505 67509 67510 67511 67549 67556 67557 67558 67573 67576 67577 67579 67591 67593 67594 67595 67596 67599 67600 67602 67610 67612 67613 67623 67624 67625 67630 67631 67632 67640 67641 67643 67644 67645 67647 67648 67649 67652 67653 67654 67656 67657 67658 67659 67661 67662 67664 67665 67668 67671 67672 67677 67678 67685 67686 67687 67688 67689 67690 67691 67693 67696 67697 67698 67699 67701 67702 67703 67704 67710 67713 67714 67715 67721 67722 67725 67726 67727 67728 67730 67731 67744 67745 67746 67747 67748 67749 67752 67753 67759 67760 67762 67763 67765 67766 67767 67768 67769 67770 67772 67773 67777 67778 67781 67782 67785 67786 67787 67788 67791 67792 67793 67794 67797 67798 67800 67801 67819 67820 67828 67829 67834 67835 67847 67848 67849 67864 67865 67868 67869 67870 67871 67872 67873 67874 67875 67876 67877 67881 67882 67883 67888 67889 67890 67891 67892 67893 67894 67895 67896 67897 67900 67901 67902 67903 67904 67905 67906 67907 67909 67912 67913 67914 67917 67918 67920 67921 67926 67930 67931 67932 67933 67935 67937 67938 67939 67940 67941 67942 67944 67945 67953 67954 67956 67957 67958 67959 67960 67961 67962 67963 67967 67968 67971 67972 67976 67977 67981 67985 67986 67988 67989 67993 67994 67996 67997 67999 68007 68008 68009 68011 68012 68013 68014 68015 68016 68020 68021 68024 68025 68026 68027 68028 68031 68032 68034 68035 68036 68037 68038 68039 68046 68047 68048 68050 68051 68052 68053 68054 68055 68056 68057 68058 68059 68061 68062 68064 68065 68066 68067 68068 68069 68070 68073 68074 68075 68080 68081 68082 68083 68084 68085 68086 68087 68088 68089 68090 68093 68094 68099 68100 68101 68102 68106 68107 68108 68109 68117 68118 68119 68120 68121 68122 68123 68124 68125 68126 68127 68128 68129 68130 68133 68136 68137 68138 68139 68144 68145 68151 68152 68153 68154 68155 68156 68157 68158 68159 68160 68161 68162 68163 68164 68165 68172 68173 68174 68175 68178 68179 68180 68181 68184 68185 68188 68189 68190 68191 68192 68193 68198 68199 68200 68201 68206 68207 68208 68209 68217 68218 68224 68225 68232 68233 68234 68235 68236 68237 68246 68247 68248 68249 68252 68253 68256 68257 68258 68259 68263 68264 68265 68267 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68597 68598 68599 68600 68601 68605 68606 68607 68608 68609 68610 68612 68613 68614 68615 68616 68617 68618 68619 68620 68621 68622 68623 68624 68625 68626 68627 68630 68631 68638 68639 68640 68641 68651 68666 68667 68678 68679 68693 68694 68710 68711 68724 68725 68727 68756 68773 68774 68778 68779 68780 68794 68795 68803 68810 68811 68829 68830 68831 68837 68838 68839 68842 68844 68845 68849 68850 68858 68863 68864 68865 68866 68867 68870 68872 68875 68876 68877 68879 68888 68889 68898 68899 68904 68919 68923 68924 68927 68928 68929 68936 68938 68939 68942 68947 68948 68949 68950 68951 68953 68954 68955 68957 68958 68959 68960 68961 68962 68963 68964 68965 68966 68969 68972 68973 68974 68977 68978 68980 68981 68982 68983 68985 68986 68990 68991 68994 68995 68996 68997 68998 68999 69000 69001 69002 69003 69004 69007 69008 69009 69010 69011 69015 69017 69021 69030 69031 69033 69034 69035 69036 69037 69040 69041 69043 69046 69048 69053 69058 69064 69073 69078 69079 69080 69085 69091 69092 69095 69100 69101 69102 69103 69107 69108 69109 69110 69111 69117 69120 69121 69125 69130 69131 69132 69134 69135 69136 69141 69142 69152 69184 69185 69189 69190 69198 69206 69208 69218 69219 69220 69221 69222 69225 69260 69261 69274 69283 69285 69286 69287 69288 69294 69295 69304 69305 69308 69309 69311 69312 69313 69314 69320 69321 69322 69325 69326 69334 69349 69352 69353 69362 69371 69375 69376 69379 69380 69381 69383 69384 69400 69424 69430 69436 69437 69440 69441 69450 69451 69452 69453 69454 69456 69457 69458 69459 69460 69466 69467 69470 69471 69472 69486 69487 69488 69490 69499 69507 69510 69511 69515 69516 69522 69528 69529 69532 69533 69537 69541 69542 69544 69545 69550 69559 69561 69562 69565 69567 69583 69584 69594 69601 69610 69615 69621 69629 69633 69634 69637 69642 69644 69650 69652 69654 69655 69656 69658 69667 69668 69678 69679 69681 69682 69683 69688 69695 69696 69705 69707 69709 69712 69719 69722 69731 69739 69740 69761 69769 69773 69778 69779 69780 69791 69792 69795 69796 69799 69803 69804 69805 69810 69812 69813 69816 69817 69818 69819 69820 69822 69823 69825 69826 69828 69829 69830 69831 69832 69834 69836 69840 69843 69846 69847 69849 69850 69854 69856 69859 69860 69861 69864 69867 69874 69876 69877 69878 69885 69886 69889 69891 69893 69895 69899 69903 69905 69906 69910 69913 69918 69921 69922 69923 69927 69928 69930 69932 69935 69936 69938 69947 69957 69965 69966 69969 69976 69996 70000 70001 70007 70008 70010 70015 70024 70025 70031 70039 70044 70050 70053 70058 70060 70069 70082 70084 70087 70088 70101 70120 70121 70123 70125 70126 70130 70131 70136 70137 70152 70164 70166 70167 70168 70172 70183 70186 70189 70196 70210 70211 70218 70227 70228 70230 70232 70237 70242 70246 70250 70251 70253 70258 70263 70265 70268 70269 70278 70302 70305 70306 70325 70327 70329 70336 70341 70362 70372 70388 70403 70404 70405 70406 70407 70410 70418 70419 70420 70423 70424 70426 70431 70432 70433 70434 70435 70437 70438 70439 70440 70441 70445 70456 70460 70472 70478 70480 70482 70499 70502 70503 70505 70512 70513 70515 70516 70517 70518 70525 70527 70528 70532 70541 70542 70545 70549 70551 70552 70567 70568 70570 70571 70572 70575 70582 70589 70596 70602 70604 70612 70615 70623 70627 70628 70629 70634 70635 70637 70643 70645 70652 70661 70672 70674 70681 70682 70683 70694 70700 70721 70724 70725 70735 70742 70753 70754 70755 70763 70764 70778 70784 70801 70810 70817 70823 70826 70831 70832 70842 70850 70871 70872 70887 70893 70900 70908 70914 70916 70924 70928 70929 70933 70936 70948 70954 70959 70973 70974 70992 70994 70997 71005 71028 71030 71032 71034 71037 71039 71040 71041 71043 71048 71049 71050 71052 71059 71060 71063 71469 71124 71694 71189 71071 71076 71079 71080 71087 71089 71090 71091 71092 71108 71112 71114 71115 71118 71124 71126 71127 71137 71138 71139 71141 71144 71155 71158 71164 71169 71172 71184 71189 71190 71191 71209 71222 71223 71224 71227 71228 71238 71239 71240 71242 71243 71244 71247 71256 71260 71264 71270 71277 71307 71308 71311 71312 71314 71315 71316 71317 71318 71319 71322 71323 71326 71327 71330 71335 71342 71351 71370 71377 71381 71384 71387 71393 71395 71397 71400 71401 71402 71407 71423 71425 71426 71433 71452 71469 71473 71474 71475 71479 71481 71490 71491 71496 71501 71510 71511 71528 71529 71532 71536 71537 71541 71545 71546 71549 71550 71552 71553 71554 71555 71557 71558 71571 71585 71586 71589 71590 71593 71599 71605 71612 71615 71616 71628 71633 71638 71640 71641 71660 71681 71683 71690 71694 71696 71698 75518 75519 75520 75521 75522 75523 75528 75530 75531 75532 75533 75534 75535 75536 75537 75538 75556 75558 75559 75563 75564 75565 75567 75568 75569 75574 75575 75579 75580 75581 75583 75591 75597 75598 75599 75607 75608 75609 75610 75617 75618 75624 75625 75633 75634 75635 75647 75648 75649 75650 75651 75652 75655 75656 75657 75662 75663 75664 75665 75666 75667 75668 75670 75671 75672 75673 75674 75675 75676 75677 75678 75684 75685 75686 75687 75688 75689 75691 75692 75693 75696 75697 75702 75703 75704 75734 75735 75736 75737 75738 75739 75740 75741 75742 75744 75745 75746 75747 75748 75749 75750 75751 75752 75756 75757 75758 75759 75760 75761 75763 75765 75769 75770 75771 75789 75790 75792 75793 75794 75795 75796 75799 75800 75802 75803 75804 75805 75806 75809 75810 75811 75813 75820 75821 75822 75831 75832 75833 75834 75845 75846 75847 75857 75873 75874 75875 75876 75877 75878 75879 75881 75882 75883 75884 75887 75894 75895 75896 75898 75899 75900 75915 75918 75919 75920 WO 2025 / 151713 46 PCT / US2025 / 011065 75921 75922 75927 75929 75930 75931 75932 75933 75934 75935 75944 75949 75950 75951 75953 75954 75955 75956 75959 75965 75966 75967 75968 75971 75972 75973 75975 75976 75977 75988 75989 75993 75994 75995 75996 75997 76008 76009 76010 76031 76032 76034 76037 76038 76039 76040 76041 76043 (22) Protein whose gene expression changes in response to lauric acid stress (SEQ ID NOs) 4449 4453 4454 4465 4503 4518 4594 4617 4618 4634 4635 4665 4679 4685 4686 4742 4744 4745 4747 4749 4750 4751 4760 4761 4763 4765 4766 4772 4786 4850 4972 4973 5120 5396 5556 5695 5815 5840 5842 5849 5897 5932 5938 5942 6013 6049 6082 6140 6141 6142 6158 6208 6218 6293 6350 6468 6475 6481 6522 6579 10271 10275 10276 10280 10281 10295 10296 10357 10369 10476 10478 10498 10514 10516 10539 10540 10580 10614 10618 10638 10640 10656 10657 10677 10723 10731 10745 10752 10855 10862 10863 10864 10905 11057 11091 11238 11311 11343 11452 11496 11594 11622 11623 11682 11684 11839 11904 11987 12018 12019 16769 16770 16771 16772 16773 16774 16775 16776 16777 16780 16782 16783 16784 16785 16786 16787 16788 16789 16790 16791 16792 16793 16794 16795 16799 16800 16801 16802 16803 16804 16805 16806 16807 16808 71282 71076 71079 71080 71081 71083 71084 71089 71090 71116 71121 71157 71159 71171 71177 71182 71184 71195 71196 71211 71218 71221 71233 71235 71243 71244 71245 71253 71262 71265 71273 71276 71282 71287 71293 71317 71319 71323 71325 71326 71327 71335 71360 71372 71383 71413 71440 71445 71461 71463 71475 71476 71494 71505 71508 71520 71560 71569 71570 71591 71593 71602 71628 71641 71650 71655 71682 71697 71698 75518 75519 75520 75521 75522 75523 75525 75526 75530 75531 75532 75566 75571 75572 75601 75602 75603 75604 75605 75606 75615 75617 75618 75626 75627 75636 75639 75646 75659 75661 75671 75672 75673 75674 75675 75682 75695 75698 75706 75750 75751 75752 75755 75756 75757 75758 75759 75760 75763 75791 75798 75839 75852 76042 75877 76043 75878 75879 75937 75943 75957 75959 75996 75997 76004 76030 Included in all nucleic acid sequences disclosed herein are DNA nucleic acid molecules, RNA nucleic acid molecules (e.g., thymidine replaced with uridine), nucleic acid molecules encoding orthologs of the encoded proteins, as well as DNA or RNA nucleic acid sequences or any variant thereof (a structural variant or a chemical variant (e.g., chemically modified nucleotide)) comprising a nucleic acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, or more identity across their full length with the nucleic acid sequence of any SEQ ID NO presented herein, or a portion thereof. Such nucleic acid molecules can have a function of the full-length nucleic acid (e.g., for the intended function of inducing an immune response) as described further herein. Included in all amino acid sequences disclosed herein are amino acid sequences or any variant thereof (a structural variant or a chemical variant) comprising an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, or more identity across their full length with the amino acid sequence of any SEQ ID NO listed in presented herein, or a portion thereof. Such polypeptides can have a function of the full-length polypeptide (e.g., for the intended function of inducing an immune response) as described further herein. HOMOLOGY Function-conservative variants are those in which a given amino acid residue in a protein or enzyme has been changed without altering the overall conformation and function of the polypeptide, including, but not limited to, replacement of an amino acid with one having similar properties (such as, for example, polarity, hydrogen bonding potential, acidic, basic, hydrophobic, aromatic, and the like). Amino acids other than those indicated as conserved may differ in a protein so that the percent protein or amino acid sequence similarity between any two proteins of similar function may vary and may be, for example, from 70% to 99% as determined according to an alignment scheme such as by the Cluster Method, wherein similarity is based on the MEGALIGN algorithm. A function-conservative variant also includes a polypeptide which has at least 60% amino acid identity as determined by BLAST or FASTA algorithms, preferably at least 75%, more preferably at least 85%, still preferably at least 90%, and even more preferably at least 95%, and which has the same or substantially similar properties or functions as the native or parent protein to which it is compared. Homology, as used herein, refers to nucleotide sequence similarity between two regions of the same nucleic acid strand or between regions of two different nucleic acid strands. When a nucleotide residue position in both regions is occupied by the same nucleotide residue, then the regions are homologous at that position. A first region is homologous to a second region if at least one nucleotide residue position of each region is occupied by the same residue. Homology between two regions is expressed in terms of the proportion of nucleotide residue positions of the two regions that are occupied by the same nucleotide residue. By way of example, a region having the nucleotide sequence 5'-ATTGCC-3' and a region having the nucleotide sequence 5'-TATGGC-3' share 50% homology. Preferably, the first region comprises a first portion and the second region comprises a second portion, whereby, at least about 50%, and preferably at least about 75%, at least about 90%, or at least about 95% of the nucleotide residue positions of each of the portions are occupied by the same nucleotide residue. More preferably, all nucleotide residue positions of each of the portions are occupied by the same nucleotide residue. For nucleic acids, the term “substantial homology” indicates that two nucleic acids, or designated sequences thereof, when optimally aligned and compared, are identical, with appropriate nucleotide insertions or deletions, in at least about 80% of the nucleotides, usually at least about 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, or more of the nucleotides, and more preferably at least about 97%, 98%, 99% or more of the nucleotides. Alternatively, substantial homology exists when the segments will hybridize under selective hybridization conditions, to the complement of the strand. The percent identity between two sequences is a function of the number of identical positions shared by the sequences ( / . e., % identity= # of identical positions / total # of positions x 100), taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences. The comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm, as described in the non-limiting examples below. The percent identity between two nucleotide sequences can be determined using the GAP program in the GCG software package (available on the world wide web at the GCG company website), using a NWSgapdna. CMP matrix and a gap weight of 40, 50, 60, 70, or 80 and a length weight of 1, 2, 3, 4, 5, or 6. The percent identity between two nucleotide or amino acid sequences can also be determined using the algorithm of E. Meyers and W. Miller (CABIOS, 4:11 17 (1989)) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. In addition, the percent identity between two amino acid sequences can be determined using the Needleman and Wunsch (J. Mol. Biol. (48):444 453 (1970)) algorithm which has been incorporated into the GAP program in the GCG software package (available on the world wide web at the GCG company website), using either a Blosum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6. The nucleic acid and protein sequences of the present invention can further be used as a “query sequence” to perform a search against public databases to, for example, identify related sequences. Such searches can be performed using the NBLAST and XBLAST programs (version 2.0) of Altschul, et al. (1990) J. Mol. Biol. 215:403 10. BLAST nucleotide searches can be performed with the NBLAST program, score=100, wordlength=12 to obtain nucleotide sequences homologous to the nucleic acid molecules of the present invention. BLAST protein searches can be performed with the XBLAST program, score=50, wordlength=3 to obtain amino acid sequences homologous to the protein molecules of the present invention. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul et aL, (1997) Nucleic Acids Res. 25(17):3389 3402. When utilizing BLAST and Gapped BLAST programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used (available on the world wide web at the NCBI website). CODON OPTIMIZA TION In preferred embodiments, the nucleic acid (e.g., DNA or RNA) vaccines of the present disclosure comprise those that are codon-optimized for expression in a host cell or a subject. Many organisms display a bias for use of particular codons to code for insertion of a particular amino acid in a growing peptide chain. Codon preference or codon bias, differences in codon usage between organisms, is afforded by degeneracy of the genetic code, and is well documented among many organisms. Codon bias often correlates with the efficiency of translation of messenger RNA (mRNA), which is in turn believed to be dependent on, inter alia, the properties of the codons being translated and the availability of particular transfer RNA (tRNA) molecules. The predominance of selected tRNAs in a cell is generally a reflection of the codons used most frequently in peptide synthesis. Accordingly, genes can be tailored for optimal gene expression in a given organism based on codon optimization. Given the large number of gene sequences available for a wide variety of animal, plant and microbial species, it is possible to calculate the relative frequencies of codon usage. Codon usage tables are readily available, for example, at the “Codon Usage Database,” available World Wide Web at kazusa.or.jp / codon / , and these tables can be adapted in a number of ways. See Nakamura, Y., et al. “Codon usage tabulated from the international DNA sequence databases: status for the year 2000” NucL Acids Res. 28:292 (2000). In preferred embodiments, codon tables from the following webiste are used: World Wide Web at kazusa.or.jp / codon / . Accordingly, the term”codon-optimized” encompasses any modification of the nucleic acid sequence to comprise at least one codon that is more frequently used in a given host cell or subject. The term “codon-optimized” is not intended to mean that all codons in the nucleic acid are optimized for expression in a given host cell or subject. POLYPEPTIDE AND / OR PEPTIDE VACCINES In certain aspects, provided herein are vaccines that utilize peptides and / or polypeptides that comprise the sequence of at least one cell surface protein of at least one methanogen, or any portion thereof. Such peptides and / or polypeptides can be chemically synthesized, or produced using an expression vector (e.g., bacteria, yeast, insect cells, mammalian cells) or in vitro translated, e.g., via methods described herein and / or those known in the art. The polypeptide and / or peptide vaccines of the present disclosure may comprise a single peptide or a single polypeptide. Alternatively, the polypeptide and / or peptide vaccines of the present disclosure may comprise a mixture of various peptides and / or polypeptides that target at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 cell surface protein of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 methanogens. In some embodiments, the polypeptide and / or peptide vaccine of the present disclosure comprises at least two different fragments of the same protein. In some embodiments, the polypeptide and / or peptide vaccine comprises at least two different fragments and / or two different polypeptides of different proteins. In some embodiments, the polypeptide and / or peptide vaccine comprises multiple fragments and / or polypeptides of different proteins of different methanogens. In some embodiments, the polypeptide and / or peptide vaccine comprises multiple fragments and / or polypeptides of different proteins of the same methanogen. In some embodiments, the polypeptide(s) / peptide(s) concentraton in a vaccine composition is from about 0.001 mg to about 500 mg per mL. In some embodiments, the concentration of the polypeptide(s) / peptide(s) in a vaccine composition is from about 0.01 mg to about 50 mg per mL. In some embodiments, the concentration range may be between about 0.1 mg and about 5 mg per mL. In some embodiments, the polypeptide(s) / peptide(s) concentration in a vaccine composition is at least about 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, 20, 20.5, 21, 21.5, 22, 22.5, 23, 23.5, 24, 24.5, 25, 25.5, 26, 26.5, 27, 27.5, 28, 28.5, 29, 29.5, 30, 30.5, 31, 31.5, 32, 32.5, 33, 33.5, 34, 34.5, 35, 35.5, 36, 36.5, 37, 37.5, 38, 38.5, 39, 39.5, 40, 40.5, 41, 41.5, 42, 42.5, 43, 43.5, 44, 44.5, 45, 45.5, 46, 46.5, 47, 47.5, 48, 48.5, 49, 49.5, or 50 mg per mL. The polypeptide and / or peptide vaccines of the present disclosure may be administered in a pharmaceutical composition described herein. The protein vaccines of the present disclosure may be administered with an adjuvant and / or other agents that enhance immune response. Multiple dosings of the protein vaccine is contemplated herein as described. PRODUCTION OF POLYPEPTIDES AND / OR PEPTIDES Methanogen proteins can be produced by recombinant DNA techniques. For example, a nucleic acid molecule encoding the protein is cloned into an expression vector, the expression vector is introduced into a host cell (as described above), and the methanogen protein is expressed in the host cell. The methanogen protein can then be isolated from the cells by an appropriate purification scheme using standard protein purification techniques. Alternative to recombinant expression, a methanogen protein, polypeptide, or peptide can be synthesized chemically using standard peptide synthesis techniques. Accordingly, the amino acid sequences disclosed herein will enable those of skill in the art to produce polypeptides corresponding peptide sequences and sequence variants thereof. Such polypeptides can be produced in host cells by expression of polynucleotides encoding the peptide sequence, frequently as part of a larger polypeptide. A host cell for expression can be any prokaryotic or eukaryotic cell. For example, protein can be expressed in bacterial cells such as E. coli, insect cells (e.g., SF9, SF21, etc.), yeast (e.g., Saccharomyces cerevisiae, Pichiapastoris, etc.) or mammalian cells (such as Fao hepatoma cells, primary hepatocytes, Chinese hamster ovary cells (CHO), COS cells, etc.). Other suitable host cells are known to those skilled in the art. Alternatively, such peptides can be synthesized by chemical methods. Methods for expression of heterologous proteins in recombinant hosts, chemical synthesis of polypeptides, and in vitro translation are well known in the art and are described further in Maniatis et al. Molecular Cloning: A Laboratory Manual (1989), 2nd Ed., Cold Spring Harbor, N.Y.; Berger and Kimmel, Methods in Enzymology, Volume 152, Guide to Molecular Cloning Techniques (1987), Academic Press, Inc., San Diego, Calif.; Merrifield, J. (1969)7. Am. Chern. Soc. 91:501; Chaiken I. M. (1981) CRC Crit. Rev. Biochem. 11: 255; Kaiser et al. (1989) Science 243:187; Merrifield, B. (1986) Science 232:342; Kent, S. B. H. (1988) Annu. Rev. Biochem. 57:957; and Offord, R. E. (1980) Semisynthetic Proteins, Wiley Publishing, which are incorporated herein by reference). Peptides can be produced, typically by direct chemical synthesis. Peptides can be produced as modified peptides, with nonpeptide moieties attached by covalent linkage to the N-terminus and / or C-terminus. In certain preferred embodiments, either the carboxy-terminus or the amino-terminus, or both, are chemically modified. The most common modifications of the terminal amino and carboxyl groups are acetylation and amidation, respectively. Aminoterminal modifications such as acylation (e.g., acetylation) or alkylation (e.g., methylation) and carboxy-terminal-modifications such as amidation, as well as other terminal modifications, including cyclization, can be incorporated into various embodiments of the invention. Certain amino-terminal and / or carboxy-terminal modifications and / or peptide extensions to the core sequence can provide advantageous physical, chemical, biochemical, and pharmacological properties, such as: enhanced stability, increased potency and / or efficacy, resistance to serum proteases, desirable pharmacokinetic properties, and others. PHARMACEUTICAL COMPOSITION Vaccines, antibodies, milk, animal feed, agents (e.g., an agent that reduces methane production in a subject, a probiotic bacterial strain, etc.), or other compositions of the present disclosure may be in a pharmaceutical composition, and thus further comprise at least one excipient and / or carrier described herein or those known in the art. The vaccine, antibody, milk, animal feed, or agent of the present disclosure (e.g., polypeptide and / or peptide vaccines) may comprise at least one excipient that (1) increases stability; (2) permits the sustained or delayed release (e.g., from a depot formulation); and / or (3) alters the biodistribution (e.g., target to specific tissues or cell types). In addition to traditional excipients such as any and all solvents, dispersion media, diluents, or other liquid vehicles, dispersion or suspension aids, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, excipients of the present disclosure include, without limitation, lipidoids, liposomes, lipid nanoparticles, polymers, lipoplexes, core-shell nanoparticles, peptides, proteins, hyaluronidase, nanoparticle mimics, and combinations thereof. Formulations of the pharmaceutical compositions described herein may be prepared by any method known or hereafter developed in the art of pharmacology. In general, such preparatory methods include the step of associating the active ingredient with an excipient and / or one or more other accessory ingredients. A pharmaceutical composition in accordance with the present disclosure may be prepared, packaged, and / or sold in bulk, as a single unit dose, and / or as a plurality of single unit doses. As used herein, a “unit dose” refers to a discrete amount of the pharmaceutical composition comprising a predetermined amount of the active ingredient (e.g., the vaccine). The amount of the active ingredient may be generally equal to the dosage of the active ingredient which would be administered to a subject and / or a convenient fraction of such a dosage such as, for example, one-half or one-third of such a dosage. Relative amounts of the active ingredient, the pharmaceutically acceptable excipient, and / or any additional ingredients in a pharmaceutical composition in accordance with the present disclosure may vary, depending upon the identity, size, and / or condition of the subject being treated and further depending upon the route by which the composition is to be administered. For example, the composition may comprise between 0.01% and 99% (w / w) of the active ingredient. By way of example, the composition may comprise between 0.01 % and 100%, e.g., between 0.05 and 50%, between 0.1-30%, between 5-80%, at least 80% (w / w) active ingredient. Pharmaceutical compositions may comprise a pharmaceutically acceptable excipient, which, as used herein, includes, but is not limited to, any and all solvents, dispersion media, diluents, or other liquid vehicles, dispersion or suspension aids, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, and the like, as suited to the particular dosage form desired. Various excipients for formulating pharmaceutical compositions and techniques for preparing the composition are known in the art (see Remington: The Science and Practice of Pharmacy, 21st Edition, A. R. Gennaro, Lippincott, Williams & Wilkins, Baltimore, MD, 2006; incorporated herein by reference in its entirety). The use of a conventional excipient medium may be contemplated within the scope of the present disclosure, except insofar as any conventional excipient medium may be incompatible with a substance or its derivatives, such as by producing any undesirable biological effect or otherwise interacting in a deleterious manner with any other component(s) of the pharmaceutical composition. Pharmaceutically acceptable excipients used in the manufacture of pharmaceutical compositions include, but are not limited to, inert diluents, surface active agents and / or emulsifiers, preservatives, buffering agents, lubricating agents, and / or oils. Such excipients may optionally be included in the pharmaceutical formulations of the invention. Controlled / sustained release In some embodiments, the compositions or agents of the present invention can be formulated for controlled release and / or targeted delivery. As used herein, “controlled release” refers to a pharmaceutical composition or compound release profile that conforms to a particular pattern of release to effect a specific outcome. In some embodiments, the compositions or agents may be encapsulated into a delivery agent described herein and / or known in the art for controlled release and / or targeted delivery. As used herein, the term “encapsulate” means to enclose, surround or encase. As it relates to the formulation of the compounds of the invention, encapsulation may be substantial, complete or partial. The term “substantially encapsulated” means that at least greater than 50, 60, 70, 80, 85, 90, 95, 96, 97, 98, 99, 99.9, 99.9 or greater than 99.999% of the pharmaceutical composition or compound of the invention may be enclosed, surrounded or encased within the delivery agent. “Partially encapsulation” means that less than 10, 10, 20, 30, 40 50 or less of the pharmaceutical composition or compound of the invention may be enclosed, surrounded or encased within the delivery agent. Advantageously, encapsulation may be determined by measuring the escape or the activity of the pharmaceutical composition or compound of the invention using fluorescence and / or electron micrograph. For example, at least 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 95, 96, 97, 98, 99, 99.9, 99.99 or greater than 99.99% of the pharmaceutical composition or compound of the invention are encapsulated in the delivery agent. In some embodiments, the controlled release formulation may include, but is not limited to, tri-block co-polymers. As a non-limiting example, the formulation may include two different types of tri-block co-polymers (International Pub. No. WO2012131104 and WO2012131106; the contents of each of which is herein incorporated by reference in its entirety). Excipients Vaccines, antibodies, milk, animal feed, agents (e.g., an agent that reduces methane production in a subject, a probiotic bacterial strain, etc.), or other compositions of the present disclosure may comprise at least one excipient and / or carrier described herein or those known in the art (e.g., a pharmaceutically acceptable excipient and / or carrier). A pharmaceutically acceptable excipient, which, as used herein, includes, but is not limited to, any and all solvents, dispersion media, diluents, or other liquid vehicles, dispersion or suspension aids, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, solid binders, lubricants, flavoring agents, stabilizers, antioxidants, osmolality adjusting agents, pH adjusting agents and the like, as suited to the particular dosage form desired. In some embodiments, one or more excipients or accessory ingredients may make up greater than 50% of the total mass or volume of a pharmaceutical composition. In some embodiments, the one or more excipients or accessory ingredients may make up at least about 50%, 60%, 70%, 80%, 90%, or more of a pharmaceutical convention. Various excipients for formulating pharmaceutical compositions and techniques for preparing the composition are known in the art (see Remington: The Science and Practice of Pharmacy, 21st Edition, A. R. Gennaro (Lippincott, Williams & Wilkins, Baltimore, MD, 2006; incorporated herein by reference in its entirety). In some embodiments, a pharmaceutically acceptable excipient may be at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% pure. In some embodiments, an excipient is approved for use for humans and for veterinary use. In some embodiments, an excipient may be approved by United States Food and Drug Administration. In some embodiments, an excipient may be of pharmaceutical grade. In some embodiments, an excipient may meet the standards of the United States Pharmacopoeia (USP), the European Pharmacopoeia (EP), the British Pharmacopoeia, and / or the International Pharmacopoeia. Pharmaceutically acceptable excipients used in the manufacture of pharmaceutical compositions include, but are not limited to, inert diluents, dispersing and / or granulating agents, surface active agents and / or emulsifiers, disintegrating agents, binding agents, preservatives, buffering agents, lubricating agents, and / or oils. Such excipients may optionally be included in pharmaceutical compositions. The composition may also include excipients such as cocoa butter and suppository waxes, coloring agents, coating agents, sweetening, flavoring, and / or perfuming agents. Exemplary diluents include, but are not limited to, calcium carbonate, sodium carbonate, calcium phosphate, dicalcium phosphate, calcium sulfate, calcium hydrogen phosphate, sodium phosphate lactose, sucrose, cellulose, microcrystalline cellulose, kaolin, mannitol, sorbitol, inositol, sodium chloride, dry starch, cornstarch, powdered sugar, etc. , and / or combinations thereof. Exemplary granulating and / or dispersing agents include, but are not limited to, potato starch, com starch, tapioca starch, sodium starch glycolate, clays, alginic acid, guar gum, citrus pulp, agar, bentonite, cellulose and wood products, natural sponge, cation-exchange resins, calcium carbonate, silicates, sodium carbonate, cross-linked poly(vinyl-pyrrolidone) (crospovidone), sodium carboxymethyl starch (sodium starch glycolate), carboxymethyl cellulose, cross- linked sodium carboxymethyl cellulose (croscarmellose), methylcellulose, pregelatinized starch (starch 1500), microcrystalline starch, water insoluble starch, calcium carboxymethyl cellulose, magnesium aluminum silicate (VEEGUM®), sodium lauryl sulfate, quaternary ammonium compounds, etc., and / or combinations thereof. Exemplary surface active agents and / or emulsifiers include, but are not limited to, natural emulsifiers (e.g. acacia, agar, alginic acid, sodium alginate, tragacanth, chondrux, cholesterol, xanthan, pectin, gelatin, egg yolk, casein, wool fat, cholesterol, wax, and lecithin), colloidal clays (e.g. bentonite [aluminum silicate] and VEEGUM® [magnesium aluminum silicate]), long chain amino acid derivatives, high molecular weight alcohols (e.g. stearyl alcohol, cetyl alcohol, oleyl alcohol, triacetin monostearate, ethylene glycol distearate, glyceryl monostearate, and propylene glycol monostearate, polyvinyl alcohol), carbomers (e.g. carboxy polymethylene, polyacrylic acid, acrylic acid polymer, and carboxyvinyl polymer), carrageenan, cellulosic derivatives (e.g. carboxymethylcellulose sodium, powdered cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose), sorbitan fatty acid esters (e.g. polyoxyethylene sorbitan monolaurate [TWEEN®20], polyoxyethylene sorbitan [TWEEN®60], polyoxyethylene sorbitan monooleate [TWEEN®80], sorbitan monopalmitate [SPAN®40], sorbitan monostearate [SPAN®60], sorbitan tristearate [SPAN®65], glyceryl monooleate, sorbitan monooleate [SPAN®80]), polyoxyethylene esters (e.g. polyoxyethylene monostearate [MYRJ®45], polyoxyethylene hydrogenated castor oil, polyethoxylated castor oil, polyoxymethylene stearate, and SOLUTOL®), sucrose fatty acid esters, polyethylene glycol fatty acid esters (e.g. CREMOPHOR®), polyoxyethylene ethers, (e.g. polyoxyethylene lauryl ether [BRU®30]), poly(vinyl-pyrrolidone), di ethylene glycol monolaurate, triethanolamine oleate, sodium oleate, potassium oleate, ethyl oleate, oleic acid, ethyl laurate, sodium lauryl sulfate, PLUORINC®F 68, POLOXAMER®188, cetrimonium bromide, cetylpyridinium chloride, benzalkonium chloride, docusate sodium, etc. and / or combinations thereof. Exemplary binding agents include, but are not limited to, starch (e.g. cornstarch and starch paste); gelatin; sugars (e.g. sucrose, glucose, dextrose, dextrin, molasses, lactose, lactitol, mannitol); amino acids (e.g., glycine); natural and synthetic gums (e.g. acacia, sodium alginate, extract of Irish moss, panwar gum, ghatti gum, mucilage of isapol husks, carboxymethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, microcrystalline cellulose, cellulose acetate, poly(vinyl-pyrrolidone), magnesium aluminum silicate (VEEGUM®), and larch arabogalactan); alginates; polyethylene oxide; polyethylene glycol; inorganic calcium salts; silicic acid; polymethacrylates; waxes; water; alcohol; etc.; and / or combinations thereof. Exemplary preservatives may include, but are not limited to, antioxidants, chelating agents, antimicrobial preservatives, antifungal preservatives, alcohol preservatives, acidic preservatives, and / or other preservatives. Oxidation is a potential degradation pathway for many compounds. In order to prevent oxidation, antioxidants can be added to the formulation. Exemplary antioxidants include, but are not limited to, alpha tocopherol, ascorbic acid, acorbyl palmitate, benzyl alcohol, butylated hydroxyanisole, EDTA, m-cresol, methionine, butylated hydroxytoluene, monothioglycerol, potassium metabisulfite, propionic acid, propyl gallate, sodium ascorbate, sodium bisulfite, sodium metabisulfite, thioglycerol and / or sodium sulfite. Exemplary chelating agents include ethylenediaminetetraacetic acid (EDTA), citric acid monohydrate, disodium edetate, dipotassium edetate, edetic acid, fumaric acid, malic acid, phosphoric acid, sodium edetate, tartaric acid, and / or trisodium edetate. Exemplary antimicrobial preservatives include, but are not limited to, benzalkonium chloride, benzethonium chloride, benzyl alcohol, bronopol, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, cresol, ethyl alcohol, glycerin, hexetidine, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric nitrate, propylene glycol, and / or thimerosal. Exemplary antifungal preservatives include, but are not limited to, butyl paraben, methyl paraben, ethyl paraben, propyl paraben, benzoic acid, hydroxybenzoic acid, potassium benzoate, potassium sorbate, sodium benzoate, sodium propionate, and / or sorbic acid. Exemplary alcohol preservatives include, but are not limited to, ethanol, polyethylene glycol, phenol, phenolic compounds, bisphenol, chlorobutanol, hydroxybenzoate, and / or phenylethyl alcohol. Exemplary acidic preservatives include, but are not limited to, vitamin A, vitamin C, vitamin E, beta-carotene, citric acid, acetic acid, dehydroacetic acid, ascorbic acid, sorbic acid, and / or phytic acid. Other preservatives include, but are not limited to, tocopherol, tocopherol acetate, deteroxime mesylate, cetrimide, butylated hydroxyanisol (BHA), butylated hydroxytoluened (BHT), ethylenediamine, sodium lauryl sulfate (SLS), sodium lauryl ether sulfate (SLES), sodium bisulfite, sodium metabisulfite, potassium sulfite, potassium metabisulfite, GLYDANT PLUS®, PHENONIP®, methylparaben, GERMALL®115, GERMABEN®, NEOLONE™, KATHON™, and / or EUXYL®. In some embodiments, the pH of the vaccine solutions are maintained between pH 5 and pH 8 to improve stability. Exemplary buffers to control pH may include, but are not limited to sodium phosphate, sodium citrate, sodium succinate, histidine (or histidine-HCl), sodium carbonate, and / or sodium malate. In another embodiment, the exemplary buffers listed above may be used with additional monovalent counterions (including, but not limited to potassium). Divalent cations may also be used as buffer counterions. Exemplary buffering agents may also include, but are not limited to, citrate buffer solutions, acetate buffer solutions, phosphate buffer solutions, ammonium chloride, calcium carbonate, calcium chloride, calcium citrate, calcium glubionate, calcium gluceptate, calcium gluconate, D-gluconic acid, calcium glycerophosphate, calcium lactate, propanoic acid, calcium levulinate, pentanoic acid, dibasic calcium phosphate, phosphoric acid, tribasic calcium phosphate, calcium hydroxide phosphate, potassium acetate, potassium chloride, potassium gluconate, potassium mixtures, dibasic potassium phosphate, monobasic potassium phosphate, potassium phosphate mixtures, sodium acetate, sodium bicarbonate, sodium chloride, sodium citrate, sodium lactate, dibasic sodium phosphate, monobasic sodium phosphate, sodium phosphate mixtures, tromethamine, magnesium hydroxide, aluminum hydroxide, alginic acid, pyrogen-free water, isotonic saline, Ringer’s solution, ethyl alcohol, etc., and / or combinations thereof. Exemplary lubricating agents include, but are not limited to, magnesium stearate, calcium stearate, stearic acid, silica, talc, malt, glyceryl behanate, hydrogenated vegetable oils, polyethylene glycol, sodium benzoate, sodium acetate, sodium chloride, leucine, magnesium lauryl sulfate, sodium lauryl sulfate, etc., and / or combinations thereof. Exemplary oils include, but are not limited to, almond, apricot kernel, avocado, babassu, bergamot, black current seed, borage, cade, camomile, canola, caraway, carnauba, castor, cinnamon, cocoa butter, coconut, cod liver, coffee, com, cotton seed, emu, eucalyptus, evening primrose, fish, flaxseed, geraniol, gourd, grape seed, hazel nut, hyssop, isopropyl myristate, jojoba, kukui nut, lavandin, lavender, lemon, litsea cubeba, macademia nut, mallow, mango seed, meadowfoam seed, mink, nutmeg, olive, orange, orange roughy, palm, palm kernel, peach kernel, peanut, poppy seed, pumpkin seed, rapeseed, rice bran, rosemary, safflower, sandalwood, sasquana, savoury, sea buckthorn, sesame, shea butter, silicone, soybean, sunflower, tea tree, thistle, tsubaki, vetiver, walnut, and wheat germ oils. Exemplary oils include, but are not limited to, butyl stearate, caprylic triglyceride, capric triglyceride, cyclomethicone, diethyl sebacate, dimethicone 360, isopropyl myristate, mineral oil, octyl dodecanol, oleyl alcohol, silicone oil, and / or combinations thereof. Excipients such as cocoa butter and suppository waxes, coloring agents, coating agents, sweetening, flavoring, and / or perfuming agents can be present in the composition. Exemplary additives include physiologically biocompatible buffers (e.g., trimethylamine hydrochloride), addition of chelants (such as, for example, DTPA or DTPA-bisamide) or calcium chelate complexes (as for example calcium DTPA, CaNaDTPA-bisamide), or, optionally, additions of calcium or sodium salts (for example, calcium chloride, calcium ascorbate, calcium gluconate or calcium lactate). In addition, antioxidants and suspending agents can be used. Cryoprotectants In some embodiments, the lipid nanoparticles and / or pharmaceutical compositions of the disclosure are refrigerated or frozen for storage and / or shipment (e.g., being stored at a temperature of 4 °C or lower, such as a temperature between about -150 °C and about 0 °C or between about -80 °C and about -20 °C (e.g., about -5 °C, -10 °C, -15 °C, -20 °C, -25 °C, -30 °C, -40 °C, -50 °C, -60 °C, -70 °C, -80 °C, -90 °C, -130 °C or -150 °C). For example, the pharmaceutical composition comprising one or more lipid nanoparticles is a solution or solid (e.g., via lyophilization) that is refrigerated for storage and / or shipment at, for example, about -20 °C, -30 °C, -40 °C, -50 °C, -60 °C, -70 °C, or -80 °C. In certain embodiments, the disclosure also relates to a method of increasing stability of the lipid nanoparticles and by storing the lipid nanoparticles and / or pharmaceutical compositions thereof at a temperature of 4 °C or lower, such as a temperature between about -150 °C and about 0 °C or between about -80 °C and about -20 °C, e.g., about -5 °C, -10 °C, -15 °C, -20 °C, -25 °C, -30 °C, -40 °C, -50 °C, -60 °C, -70 °C, -80 °C, -90 °C, -130 °C or -150 °C). In some embodiments, vaccine formulations may comprise cyroprotectants. As used herein, there term “cryoprotectant” refers to one or more agent that when combined with a given substance, helps to reduce or eliminate damage to that substance that occurs upon freezing. In some embodiments, cryoprotectants are combined with vaccines in order to stabilize them during freezing. Frozen storage of vaccines between -20°C and -80°C may be advantageous for long term (e.g., 36 months) storage. In some embodiments, cryoprotectants are included in vaccine formulations through freeze / thaw cycles and under frozen storage conditions. Cryoprotectants of the present invention may include, but are not limited to sucrose, trehalose, lactose, glycerol, dextrose, raffinose and / or mannitol. Trehalose is listed by the Food and Drug Administration as being generally regarded as safe (GRAS) and is commonly used in commercial pharmaceutical formulations. Inactive Ingredients In some embodiments, vaccine formulations may comprise at least one excipient which is an inactive ingredient. As used herein, ther term "inactive ingredient" refers to one or more inactive agents included in formulations. Exemplary non-exhaustive lists of inactive ingredients and the routes of administration the inactive ingredients may be formulated in are described in Tables 7-8. Table 7. Exemplary inactive ingredients Inactive Ingredient Route of Administration Alpha-Terpineol Topical Alpha-Tocopherol Intravenous; Topical Alpha-Tocopherol Acetale, DI- Topical Alpha-Tocopherol, DI- Intravenous; Topical 1,2,6-Hexauetriol Topical l,2-Dimyristoyl-Sn-Glycero-3-(Phospho-S- (1-Glycerol)) Intravenous; Infusion (IV) l,2-Dimyristoyl-Sn-Glyccro-3-Phosphocholine Intravenous; Infusion (IV) l,2-Diolcoyl-Sn-Glyccro-3-Phosphocholinc Epidural l,2-Dipalmitoyl-Sn-Glycero-3-(Phospho- Rac-(1-Glycerol)) Epidural l,2-Distearoyl-Sn-Glycero-3-(Phospho-Rac-(1-Glycerol)) Intravenous l,2-Distearoyl-Sn-Glycero-3-Phosphocholine Intravenous 1 -O-Tolylbiguanide Topical Table 8. Exemplary inactive ingredients Route of Administration Inactive Ingredient Intrathecal (AN, CNBLK) Acetone Sodium Bisulfite; Citric Acid; Hydrochloric Acid; Sodium Chloride; Sodium Hydroxide; Sodium Metabisulfite Infiltration (AN) Acetic Acid; Acetone Sodium Bisulfite; Ascorbic Acid; Benzyl Alcohol; Calcium Chloride; Carbon Dioxide; Chlorobutanol; Citric Acid; Citric Acid Monohydratc; Edetate Calcium Disodium; Edetate Disodium; Hydrochloric Acid; Hydrochloric Acid, Diluted; Lactic Acid; Methylparaben; Monothioglycerol; Nitrogen; Potassium Chloride; Potassium Metabisulfite; Potassium Phosphate, Monobasic; Propylparaben; Sodium Bisulfite; Sodium Carbonate; Sodium Chlorate; Sodium Chloride; Sodium Citrate; Sodium Hydroxide; Sodium Lactate; Sodium Metabisulfite; Sodium Phosphate, Dibasic, Heptahydrate Sympathetic NBLK (AN) Hydrochloric Acid; Sodium Chloride; Sodium Hydroxide Auricular (Otic) Acetic Acid; Aluminum Acetate; Aluminum Sulfate Anhydrous; Benzalkonium Chloride; Benzethonium Chloride; Benzyl Alcohol; Boric Acid; Calcium Carbonate; Cetyl Alcohol; Chlorobutanol; Chloroxylenol; Citric Acid; Creatinine; Cupric Sulfate; Cupric Sulfate Anhydrous; Edetate Disodium; Edetic Acid; Glycerin; Glyceryl Stearate; Hydrochloric Acid; Hydrocortisone; Hydroxyethyl Cellulose; Isopropyl Myristate; Lactic Acid; lecithin, Hydrogenated; Mcthylparabcn; Mineral Oil; Petrolatum; Petrolatum, White; Phenylethyl Alcohol; Polyoxyl 40 Stearate; Polyoxyl Stearate; Polysorbate 20; Polysorbate 80; Polyvinyl Alcohol; Potassium Metabisulfite; Potassium Phosphate, Monobasic; Povidone K901; Povidones; Propylene Glycol; Propylene Glycol Diacctate; Propylparaben; Sodium Acetate; Sodium Bisulfite; Sodium Borate; Sodium Chloride; Sodium Citrate; Sodium Hydroxide; Sodium Phosphate, Dibasic, Anhydrous; Sodium Phosphate, Dibasic, Ileptahydrate; Sodium Phosphate, Monobasic, Anhydrous; Sodium In Table 8, "AN" means anesthetic, "CNBLK" means cervical nerve block, "NBLK" means nerve block, and "IV" means intravenous. Naked delivery The compositions or agents of the present invention may be delivered to a subject naked or in saline. The naked compositions or agents may be administered to a subject using routes of administration known in the art and described herein. ADMINISTRA TION Vaccines, antibodies, milk, animal feed, agents (e.g., an agent that reduces methane production in a subject, a probiotic bacterial strain, a small molecule inhibitor, etc.), or other compositions of the present disclosure (e.g., those reducing methane production in a subject) may be administered to a subject by any route which results in a therapeutically effective outcome. These include, but are not limited to, enteral (into the intestine), gastroenteral, epidural (into the dura matter), oral (by way of the mouth), transdermal, peridural, intracerebral (into the cerebrum), intracerebroventricular (into the cerebral ventricles), epicutaneous (application onto the skin), intradermal, (into the skin itself), subcutaneous (under the skin), nasal administration (through the nose), intravenous (into a vein), intravenous bolus, intravenous drip, intraarterial (into an artery), intramuscular (into a muscle), intracardiac (into the heart), intraosseous infusion (into the bone marrow), intrathecal (into the spinal canal), intraperitoneal, (infusion or injection into the peritoneum), intravesical infusion, intravitreal, (through the eye), intracavernous injection (into a pathologic cavity) intracavitary (into the base of the penis), intravaginal administration, intrauterine, extra-amniotic administration, transdermal (diffusion through the intact skin for systemic distribution), transmucosal (diffusion through a mucous membrane), transvaginal, insufflation (snorting), sublingual, sublabial, enema, eye drops (onto the conjunctiva), in ear drops, auricular (in or by way of the ear), buccal (directed toward the cheek), conjunctival, cutaneous, dental (to a tooth or teeth), electro-osmosis, endocervical, endosinusial, endotracheal, extracorporeal, hemodialysis, infiltration, interstitial, intraabdominal, intra-amniotic, intra- articular, intrabiliary, intrabronchial, intrabursal, intracartilaginous (within a cartilage), intracaudal (within the cauda equine), intracistemal (within the cisterna magna cerebellomedularis), intracorneal (within the cornea), dental intracornal, intracoronary (within the coronary arteries), intracorporus cavernosum (within the dilatable spaces of the corporus cavernosa of the penis), intradiscal (within a disc), intraductal (within a duct of a gland), intraduodenal (within the duodenum), intradural (within or beneath the dura), intraepidermal (to the epidermis), intraesophageal (to the esophagus), intragastric (within the stomach), intragingival (within the gingivae), intraileal (within the distal portion of the small intestine), intralesional (within or introduced directly to a localized lesion), intraluminal (within a lumen of a tube), intralymphatic (within the lymph), intramedullary (within the marrow cavity of a bone), intrameningeal (within the meninges), intraocular (within the eye), intraovarian (within the ovary), intrapericardial (within the pericardium), intrapleural (within the pleura), intraprostatic (within the prostate gland), intrapulmonary (within the lungs or its bronchi), intrasinal (within the nasal or periorbital sinuses), intraspinal (within the vertebral column), intrasynovial (within the synovial cavity of a joint), intratendinous (within a tendon), intratesticular (within the testicle), intrathecal (within the cerebrospinal fluid at any level of the cerebrospinal axis), intrathoracic (within the thorax), intratubular (within the tubules of an organ), intratumor (within a tumor), intratympanic (within the auras media), intravascular (within a vessel or vessels), intraventricular (within a ventricle), iontophoresis (by means of electric current where ions of soluble salts migrate into the tissues of the body), irrigation (to bathe or flush open wounds or body cavities), laryngeal (directly upon the larynx), nasogastric (through the nose and into the stomach), occlusive dressing technique, ophthalmic (to the external eye), oropharyngeal (directly to the mouth and pharynx), parenteral, percutaneous, periarticular, peridural, perineural, periodontal, rectal, respiratory (within the respiratory tract by inhaling orally or nasally for local or systemic effect), retrobulbar (behind the pons or behind the eyeball), intramyocardial (entering the myocardium), soft tissue, subarachnoid, subconjunctival, submucosal, transplacental (through or across the placenta), transtracheal (through the wall of the trachea), transtympanic (across or through the tympanic cavity), ureteral (to the ureter), urethral (to the urethra), vaginal, caudal block, diagnostic, nerve block, biliary perfusion, cardiac perfusion, photopheresis or spinal. In specific embodiments, compositions may be administered in a way which allows them cross the blood-brain barrier, vascular barrier, or other epithelial barrier. Non-limiting routes of administration for the compositions or agents of the present disclosure are described below. Parenteral and injectable administration Liquid dosage forms for parenteral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and / or elixirs. In addition to active ingredients, liquid dosage forms may comprise inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, oral compositions can include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and / or perfuming agents. In certain embodiments for parenteral administration, compositions are mixed with solubilizing agents such as CREMOPHOR®, alcohols, oils, modified oils, glycols, polysorbates, cyclodextrins, polymers, and / or combinations thereof. A pharmaceutical composition for parenteral administration may comprise at least one inactive ingredient. A non- exhaustive list of inactive ingredients for use in pharmaceutical compositions for parenteral administration includes hydrochloric acid, mannitol, nitrogen, sodium acetate, sodium chloride and sodium hydroxide. Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing agents, wetting agents, and / or suspending agents. Sterile injectable preparations may be sterile injectable solutions, suspensions, and / or emulsions in nontoxic parenterally acceptable diluents and / or solvents, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, U.S. P., and isotonic sodium chloride solution. Sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. Fatty acids such as oleic acid can be used in the preparation of injectables. The sterile formulation may also comprise adjuvants such as local anesthetics, preservatives and buffering agents. Injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, and / or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use. Injectable formulations may be for direct injection into a region of a tissue, organ and / or subject. As a non-limiting example, a tissue, organ and / or subject may be directly injected a formulation by intramyocardial injection into the ischemic region. (See e.g., Zangi et al. Nature Biotechnology 2013; the contents of which are herein incorporated by reference in its entirety). In order to prolong the effect of an active ingredient, it is often desirable to slow the absorption of the active ingredient from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactidepolyglycolide. Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are prepared by entrapping the drug in liposomes or microemulsions which are compatible with body tissues. Rectal and Vaginal Administration Compositions for rectal or vaginal (e.g., transvaginal) administration are typically suppositories which can be prepared by mixing compositions with suitable non-irritating excipients such as cocoa butter, polyethylene glycol or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active ingredient. As a non-limiting example, the formulations for rectal and / or vaginal administration may be prepared by mixing the drug with a suitable non-irritating excipient that is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum and / or vagina to release the drug. Such materials include cocoa butter and polyethylene glycols. A pharmaceutical composition for rectal administration may comprise at least one inactive ingredient. A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for rectal administration includes alcohol, alcohol, dehydrated, aluminum subacetate, anhydrous citric acid, aniseed oil, ascorbic acid, ascorbyl palmitate, balsam peru, benzoic acid, benzyl alcohol, bismuth subgallate, butylated hydroxyanisole, butylated hydroxytoluene, butylparaben, caramel, carbomer 934, carbomer 934p, carboxypolymethylene, cerasynt-se, cetyl alcohol, cocoa butter, coconut oil, hydrogenated, coconut oil / palm kernel oil glycerides, hydrogenated, cola nitida seed extract, d&c yellow no. 10, dichlorodifluoromethane, di chlorotetrafluoroethane, dimethyldioctadecylammonium bentonite, edetate calcium disodium, edetate disodium, edetic acid, epilactose, ethylenediamine, fat, edible, fat, hard, fd&c blue no. 1, fd&c green no. 3, fd&c yellow no. 6, flavor fig 827118, flavor raspberry pfc-8407, fructose, galactose, glycerin, glyceryl palmitate, glyceryl stearate, glyceryl stearate / peg stearate, glyceryl stearate / peg-40 stearate, glycine, hydrocarbon, hydrochloric acid, hydrogenated palm oil, hypromelloses, lactose, lanolin, lecithin, light mineral oil, magnesium aluminum silicate, magnesium aluminum silicate hydrate, methylparaben, nitrogen, palm kernel oil, paraffin, petrolatum, white, polyethylene glycol 1000, polyethylene glycol 1540, polyethylene glycol 3350, polyethylene glycol 400, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 8000, polysorbate 60, polysorbate 80, potassium acetate, potassium metabisulfite, propylene glycol, propylparaben, saccharin sodium, saccharin sodium anhydrous, silicon dioxide, colloidal, simethicone, sodium benzoate, sodium carbonate, sodium chloride, sodium citrate, sodium hydroxide, sodium metabisulfite, sorbitan monooleate, sorbitan sesquioleate, sorbitol, sorbitol solution, starch, steareth-10, steareth-40, sucrose, tagatose, d-, tartaric acid, dl-, trolamine, tromethamine, vegetable oil glyceride, hydrogenated, vegetable oil, hydrogenated, wax, emulsifying, white wax, xanthan gum and zinc oxide. A pharmaceutical composition for vaginal administration may comprise at least one inactive ingredient. Any or none of the inactive ingredients used may have been approved by the US Food and Drug Administration (FDA). A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for vaginal administration includes adipic acid, alcohol, denatured, allantoin, anhydrous lactose, apricot kernel oil peg-6 esters, barium sulfate, beeswax, bentonite, benzoic acid, benzyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, calcium lactate, carbomer 934, carbomer 934p, cellulose, microcrystalline, ceteth-20, cetostearyl alcohol, cetyl alcohol, cetyl esters wax, cetyl palmitate, cholesterol, choleth, citric acid, citric acid monohydrate, coconut oil / palm kernel oil glycerides, hydrogenated, crospovidone, edetate disodium, ethylcelluloses, ethylene-vinyl acetate copolymer (28% vinyl acetate), ethylene-vinyl acetate copolymer (9% vinylacetate), fatty alcohols, fd&c yellow no. 5, gelatin, glutamic acid, dl-, glycerin, glyceryl isostearate, glyceryl monostearate, glyceryl stearate, guar gum, high density polyethylene, hydrogel polymer, hydrogenated palm oil, hypromellose 2208 (15000 mpa.s), hypromelloses, isopropyl myristate, lactic acid, lactic acid, dl-, lactose, lactose monohydrate, lactose, hydrous, lanolin, lanolin anhydrous, lecithin, lecithin, soybean, light mineral oil, magnesium aluminum silicate, magnesium aluminum silicate hydrate, magnesium stearate, methyl stearate, methylparaben, microcrystalline wax, mineral oil, nitric acid, octyl dodecanol, peanut oil, peg 6-32 stearate / glycol stearate, peg-100 stearate, peg-120 glyceryl stearate, peg-2 stearate, peg-5 oleate, pegoxol 7 stearate, petrolatum, white, phenylmercuric acetate, phospholipon 90g, phosphoric acid, piperazine hexahydrate, poly(dimethylsiloxane / methylvinylsiloxane / methylhydrogensiloxane) dimethylvinyl or dimethylhydroxy or trimethyl endblocked, polycarbophil, polyester, polyethylene glycol 1000, polyethylene glycol 3350, polyethylene glycol 400, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 8000, polyglyceryl-3 oleate, polyglyceryl-4 oleate, polyoxyl palmitate, polysorbate 20, polysorbate 60, polysorbate 80, polyurethane, potassium alum, potassium hydroxide, povidone k29 / 32, povidones, promulgen d, propylene glycol, propylene glycol monopalmitostearate, propylparaben, quatemium-15 cis-form, silicon dioxide, silicon dioxide, colloidal, silicone, sodium bicarbonate, sodium citrate, sodium hydroxide, sodium lauryl sulfate, sodium metabisulfite, sodium phosphate, dibasic, anhydrous, sodium phosphate, monobasic, anhydrous, sorbic acid, sorbitan monostearate, sorbitol, sorbitol solution, spermaceti, stannous 2-ethylhexanoate, starch, starch 1500, pregelatinized, starch, corn, stearamidoethyl diethylamine, stearic acid, stearyl alcohol, tartaric acid, dl-, tert- butylhydroquinone, tetrapropyl orthosilicate, trolamine, urea, vegetable oil, hydrogenated, wecobee fs, white ceresin wax and white wax. Oral Administration Liquid dosage forms for oral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and / or elixirs. In addition to active ingredients, liquid dosage forms may comprise inert diluents and / or excipients commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, oral compositions can include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and / or perfuming agents. In certain embodiments for parenteral administration, compositions are mixed with solubilizing agents such as CREMOPHOR®, alcohols, oils, modified oils, glycols, polysorbates, cyclodextrins, polymers, and / or combinations thereof. Syrups and elixirs can be formulated with sweetening agents, for example glycerol, propylene glycol, sorbitol, glucose or sucrose. Such formulations can also contain a demulcent, a preservative and flavoring and coloring agents. The pharmaceutical compositions can be in the form of a sterile injectable aqueous or oleaginous suspension. This suspension can be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents that have been mentioned above. The sterile injectable preparation can also be a sterile injectable solution or suspension in a non-toxic parentally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that can be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables. Suspensions for oral dosage may contain the active materials in a mixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients may be suspending agents, as a non-limiting example the suspending agents may be sodium carboxymethylcellulose, methylcellulose, hydropropyl-methylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents can be a naturally-occurring phosphatide, for example, lecithin, or condensation products of an alkylene oxide with fatty acids, for example polyoxyethylene stearate; or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example polyethylene sorbitan monooleate. The aqueous suspensions may also contain one or more preservatives, for example ethyl, or n-propyl p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents, and one or more sweetening agents, such as sucrose or saccharin. Oily suspensions for oral dosage can be formulated by suspending the active ingredients in a vegetable oil, for example arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin. The oily suspensions can contain a thickening agent, for example beeswax, hard paraffin or cetyl alcohol. Sweetening agents and flavoring agents can be added to provide palatable oral preparations. These compositions can be preserved by the addition of an anti-oxidant such as ascorbic acid. The oral dosage may also be in the form of oil-in-water emulsions. The oily phase can be a vegetable oil or a mineral oil or mixtures of these. Suitable emulsifying agents can be naturally- occurring gums, for example gum acacia or gum tragacanth, naturally- occurring phosphatides, for example soy bean, lecithin, and esters or partial esters derived from fatty acids and hexitol, anhydrides, for example sorbitan monooleate, and condensation products of the said partial esters with ethylene oxide, for example polyoxyethylene sorbitan monooleate. The emulsions may also contain sweetening and flavoring agents. Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, an active ingredient is mixed with at least one inert, pharmaceutically acceptable excipient such as sodium citrate or dicalcium phosphate and / or fillers or extenders (e.g. starches, lactose, sucrose, glucose, mannitol, and silicic acid), binders (e.g. carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia), humectants (e.g. glycerol), disintegrating agents (e.g. agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate), solution retarding agents (e.g. paraffin), absorption accelerators (e.g. quaternary ammonium compounds), wetting agents (e.g. cetyl alcohol and glycerol monostearate), absorbents (e.g. kaolin and bentonite clay), and lubricants (e.g. talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate), and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may comprise buffering agents. The solid dosage forms may also dissolve once they come in contact with liquid such as, but not limited to, salvia and bile. Compositions intended for oral use can be prepared according to any method known to the art for the manufacture of pharmaceutical compositions and such compositions can contain one or more such sweetening agents, flavoring agents, coloring agents or preservative agents in order to provide pharmaceutically elegant and palatable preparations. Solid dosage forms may be uncoated or they can be coated by known techniques. In some cases such coatings can be prepared by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monosterate or glyceryl distearate can be employed. Formulations for oral use can also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example peanut oil, liquid paraffin or olive oil. Dosage forms for oral delivery may also be chewable. The chewable dosages forms may be sustained release formulations such as, but not limited to, the sustained release compositions described in International Publication No WO2013082470 and US Publication No US20130142876, each of which is herein incorporated by reference in its entirety. The chewable dosage forms may comprise amphipathic lipids such as, but not limited to, those described in International Publication No WO2013082470 and US Publication No US20130142876, each of which is herein incorporated by reference in its entirety. Topical or Transdermal Administration As described herein, compositions of the present disclosure may be formulated for administration transdermally. The skin may be an ideal target site for delivery as it is readily accessible. Gene expression may be restricted not only to the skin, potentially avoiding nonspecific toxicity, but also to specific layers and cell types within the skin. The site of cutaneous expression of the delivered compositions will depend on the route of delivery. Two routes are commonly considered to deliver compositions to the skin: (ii) intradermal injection; and (iii) systemic delivery (e.g. for treatment of dermatologic diseases that affect both cutaneous and extracutaneous regions). Compositions can be delivered to the skin by several different approaches known in the art. In some embodiments, the invention provides for the compositions or agents to be delivered in more than one injection. In some embodiments, before transdermal administration at least one area of tissue, such as skin, may be subjected to a device and / or solution which may increase permeability. In one embodiment, the tissue may be subjected to an abrasion device to increase the permeability of the skin (see U.S. Patent Publication No. 20080275468, herein incorporated by reference in its entirety). In another embodiment, the tissue may be subjected to an ultrasound enhancement device. An ultrasound enhancement device may include, but is not limited to, the devices described in U.S. Publication No. 20040236268 and U.S. Patent Nos. 6,491,657 and 6,234,990; each of which are herein incorporated by reference in their entireties. Methods of enhancing the permeability of tissue are described in U.S. Publication Nos. 20040171980 and 20040236268 and U.S. Pat. No. 6,190,315; each of which are herein incorporated by reference in their entireties. In some embodiments, a device may be used to increase permeability of tissue before delivering formulations of compositions described herein. The permeability of skin may be measured by methods known in the art and / or described in U.S. Patent No. 6,190,315, herein incorporated by reference in its entirety. As a non-limiting example, a formulation may be delivered by the drug delivery methods described in U.S. Patent No. 6,190,315, herein incorporated by reference in its entirety. In another non-limiting example tissue may be treated with a eutectic mixture of local anesthetics (EMLA) cream before, during and / or after the tissue may be subjected to a device which may increase permeability. Katz et al. (Anesth Analg (2004); 98:371-76; herein incorporated by reference in its entirety) showed that using the EMLA cream in combination with a low energy, an onset of superficial cutaneous analgesia was seen as fast as 5 minutes after a pretreatment with a low energy ultrasound. In some embodiments, enhancers may be applied to the tissue before, during, and / or after the tissue has been treated to increase permeability. Enhancers include, but are not limited to, transport enhancers, physical enhancers, and cavitation enhancers. Non-limiting examples of enhancers are described in U.S. Patent No. 6,190,315, herein incorporated by reference in its entirety. In some embodiments, a device may be used to increase permeability of tissue before delivering formulations of compositions described herein, which may further contain a substance that invokes an immune response. In another non-limiting example, a formulation containing a substance to invoke an immune response may be delivered by the methods described in U.S. Publication Nos. 20040171980 and 20040236268; each of which are herein incorporated by reference in their entireties. Dosage forms for transdermal administration of a composition may include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants and / or patches. Generally, an active ingredient is admixed under sterile conditions with a pharmaceutically acceptable excipient and / or any needed preservatives and / or buffers as may be required. Additionally, the compositions of the present disclosure contemplates the use of transdermal patches, which often have the added advantage of providing controlled delivery of a compound to the body. Such dosage forms may be prepared, for example, by dissolving and / or dispensing the compound in the proper medium. Alternatively or additionally, rate may be controlled by either providing a rate controlling membrane and / or by dispersing the compound in a polymer matrix and / or gel. A pharmaceutical composition for transdermal administration may comprise at least one inactive ingredient. A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for transdermal administration includes acrylates copolymer, acrylic acid-isooctyl acrylate copolymer, acrylic adhesive 788, adcote 72al03, aerotex resin 3730, alcohol, alcohol, dehydrated, aluminum polyester, bentonite, butylated hydroxytoluene, butylene glycol, butyric acid, caprylic / capric triglyceride, carbomer 1342, carbomer 940, carbomer 980, carrageenan, cetylpyridinium chloride, citric acid, crospovidone, daubert 1-5 pestr (matte) 164z, di ethylene glycol monoethyl ether, di ethylhexyl phthalate, dimethicone copolyol, dimethicone mdx4-4210, dimethicone medical fluid 360, dimethylaminoethyl methacrylate - butyl methacrylate - methyl methacrylate copolymer, dipropylene glycol, duro-tak 280-2516, duro-tak 387-2516, duro-tak 80- 1196, duro-tak 87-2070, duro-tak 87-2194, duro-tak 87-2287, duro-tak 87-2296, duro- tak 87-2888, duro-tak 87-2979, edetate disodium, ethyl acetate, ethyl oleate, ethylcelluloses, ethylene vinyl acetate copolymer, ethylene-propylene copolymer, fatty acid esters, gelva 737, glycerin, glyceryl laurate, glyceryl oleate, heptane, high density polyethylene, hydrochloric acid, hydrogenated polybutene 635-690, hydroxy ethyl cellulose, hydroxypropyl cellulose, isopropyl myristate, isopropyl palmitate, lactose, lanolin anhydrous, lauryl lactate, lecithin, levulinic acid, light mineral oil, medical adhesive modified s-15, methyl alcohol, methyl laurate, mineral oil, nitrogen, octisalate, octyl dodecanol, oleic acid, oleyl alcohol, oleyl oleate, pentadecalactone, petrolatum, white, polacrilin, polyacrylic acid (250000 mw), polybutene (1400 mw), polyester, polyester polyamine copolymer, polyester rayon, polyethylene terephthalates, polyisobutylene, polyisobutylene (1100000 mw), polyisobutylene (35000 mw), polyisobutylene 178-236, polyisobutylene 241-294, polyisobutylene 35-39, polyisobutylene low molecular weight, polyisobutylene medium molecular weight, polyisobutylene / polybutene adhesive, polypropylene, polyvinyl acetate, polyvinyl alcohol, polyvinyl chloride, polyvinyl chloride -polyvinyl acetate copolymer, polyvinylpyridine, povidone k29 / 32, povidones, propylene glycol, propylene glycol monolaurate, ra-2397, ra-3011, silicon, silicon dioxide, colloidal, silicone, silicone adhesive 4102, silicone adhesive 4502, silicone adhesive bio-psa q7- 4201, silicone adhesive bio-psa q7-4301, silicone / polyester film strip, sodium chloride, sodium citrate, sodium hydroxide, sorbitan monooleate, stearalkonium hectorite / propylene carbonate, titanium dioxide, triacetin, trolamine, tromethamine, union 76 amsco-res 6038 and viscose / cotton. A pharmaceutical composition for intradermal administration may comprise at least one inactive ingredient. A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for intradermal administration includes benzalkonium chloride, benzyl alcohol, carboxymethylcellulose sodium, creatinine, edetate disodium, glycerin, hydrochloric acid, metacresol, methylparaben, phenol, polysorbate 80, protamine sulfate, sodium acetate, sodium bisulfite, sodium chloride, sodium hydroxide, sodium phosphate, sodium phosphate, dibasic, sodium phosphate, dibasic, heptahydrate, sodium phosphate, monobasic, anhydrous and zinc chloride. Depot Administration As described herein, in some embodiments, the composition is formulated in depots for extended release. Generally, a specific organ or tissue (a "target tissue") is targeted for administration. In some aspects, the compositions or agents are spatially retained within or proximal to a target tissue. Provided are method of providing a composition to a target tissue of a mammalian subject by contacting the target tissue (which contains one or more target cells) with the composition under conditions such that the composition is substantially retained in the target tissue, meaning that at least 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 95, 96, 97, 98, 99, 99.9, 99.99 or greater than 99.99% of the composition is retained in the target tissue. Aspects of the invention are directed to methods of providing a composition to a target tissue of a subject, by contacting the target tissue (comprising one or more target cells) with the composition under conditions such that the composition is substantially retained in the target tissue. In some embodiments, the compositions may be retained near target tissue using a small disposable drug reservoir, patch pump or osmotic pump. Non-limiting examples of patch pumps include those manufactured and / or sold by BD® (Franklin Lakes, NJ), Insulet Corporation (Bedford, MA), SteadyMed Therapeutics (San Francisco, CA), Medtronic (Minneapolis, MN) (e.g., MiniMed), UniLife (York, PA), Valeritas (Bridgewater, NJ), and SpringLeaf Therapeutics (Boston, MA). A non- limiting example of an osmotic pump include those manufactured by DURECT® (Cupertino, CA) (e.g, DUROS® and ALZET ®). Pulmonary Administration A pharmaceutical composition may be prepared, packaged, and / or sold in a formulation suitable for pulmonary administration via the buccal cavity. Such a formulation may comprise dry particles which comprise the active ingredient and which have a diameter in the range from about 0.5 nm to about 7 nm or from about 1 nm to about 6 nm. Such compositions are suitably in the form of dry powders for administration using a device comprising a dry powder reservoir to which a stream of propellant may be directed to disperse the powder and / or using a self propelling solvent / powder dispensing container such as a device comprising the active ingredient dissolved and / or suspended in a low-boiling propellant in a sealed container. Such powders comprise particles wherein at least 98% of the particles by weight have a diameter greater than 0.5 nm and at least 95% of the particles by number have a diameter less than 7 nm. Alternatively, at least 95% of the particles by weight have a diameter greater than 1 nm and at least 90% of the particles by number have a diameter less than 6 nm. Dry powder compositions may include a solid fine powder diluent such as sugar and are conveniently provided in a unit dose form. Low boiling propellants generally include liquid propellants having a boiling point of below 65 °F at atmospheric pressure. Generally the propellant may constitute 50% to 99.9% (w / w) of the composition, and active ingredient may constitute 0.1% to 20% (w / w) of the composition. A propellant may further comprise additional ingredients such as a liquid non-ionic and / or solid anionic surfactant and / or a solid diluent (which may have a particle size of the same order as particles comprising the active ingredient). As a non-limiting example, the compositions described herein may be formulated for pulmonary delivery by the methods described in U.S. Pat. No. 8,257,685; herein incorporated by reference in its entirety. Pharmaceutical compositions formulated for pulmonary delivery may provide an active ingredient in the form of droplets of a solution and / or suspension. Such formulations may be prepared, packaged, and / or sold as aqueous and / or dilute alcoholic solutions and / or suspensions, optionally sterile, comprising active ingredient, and may conveniently be administered using any nebulization and / or atomization device. Such formulations may further comprise one or more additional ingredients including, but not limited to, a flavoring agent such as saccharin sodium, a volatile oil, a buffering agent, a surface active agent, and / or a preservative such as methylhydroxybenzoate. Droplets provided by this route of administration may have an average diameter in the range from about 0.1 nm to about 200 nm. The compositions and formulations provided herein which may be used for pulmonary delivery may further comprise one or more surfactants. Suitable surfactants or surfactant components for enhancing the uptake of the compositions of the invention include synthetic and natural as well as full and truncated forms of surfactant protein A, surfactant protein B, surfactant protein C, surfactant protein D and surfactant Protein E, di-saturated phosphatidylcholine (other than dipalmitoyl), dipalmitoylphosphatidylcholine, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine; phosphatidic acid, ubiquinones, lysophosphatidylethanolamine, lysophosphatidylcholine, palmitoyl-lysophosphatidylcholine, dehydroepiandrosterone, dolichols, sulfatidic acid, glycerol-3-phosphate, dihydroxyacetone phosphate, glycerol, glycero-3-phosphocholine, dihydroxyacetone, palmitate, cytidine diphosphate (CDP) diacylglycerol, CDP choline, choline, choline phosphate; as well as natural and artificial lamellar bodies which are the natural carrier vehicles for the components of surfactant, omega-3 fatty acids, polyenic acid, polyenoic acid, lecithin, palmitinic acid, non-ionic block copolymers of ethylene or propylene oxides, polyoxypropylene, monomeric and polymeric, polyoxyethylene, monomelic and polymeric, poly(vinyl amine) with dextran and / or alkanoyl side chains, Brij 35, Triton X-100 and synthetic surfactants ALEC, Exosurf, Survan and Atovaquone, among others. These surfactants can be used either as single or part of a multiple component surfactant in a formulation, or as covalently bound to a component of a pharmaceutical composition herein. Intranasal, nasal and buccal Administration Formulations described herein as being useful for pulmonary delivery are useful for intranasal delivery of a pharmaceutical composition. Another formulation suitable for intranasal administration is a coarse powder comprising the active ingredient and having an average particle from about 0.2 pu] to 500 piq. Such a formulation is administered in the manner in which snuff is taken, i.e. by rapid inhalation through the nasal passage from a container of the powder held close to the nose. Formulations suitable for nasal administration may, for example, comprise from about as little as 0.1% (w / w) and as much as 100% (w / w) of active ingredient, and may comprise one or more of the additional ingredients described herein. A pharmaceutical composition may be prepared, packaged, and / or sold in a formulation suitable for buccal administration. Such formulations may, for example, be in the form of tablets and / or lozenges made using conventional methods and may, for example, 0.1% to 20% (w / w) active ingredient, the balance comprising an orally dissolvable and / or degradable composition and, optionally, one or more of the additional ingredients described herein. Alternately, formulations suitable for buccal administration may comprise a powder and / or an aerosolized and / or atomized solution and / or suspension comprising active ingredient. Such powdered, aerosolized, and / or aerosolized formulations, when dispersed, may have an average particle and / or droplet size in the range from about 0.1 nm to about 200 nm, and may further comprise one or more of any additional ingredients described herein. A pharmaceutical composition for inhalation (respiratory) administration may comprise at least one inactive ingredient. A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for inhalation (respiratory) administration includes acetone sodium 73 bisulfite, acetylcysteine, alcohol, alcohol, dehydrated, ammonia, apaflurane, ascorbic acid, benzalkonium chloride, calcium carbonate, carbon dioxide, cetylpyridinium chloride, chlorobutanol, citric acid, d&c yellow no. 10, dichlorodifluoromethane, di chlorotetrafluoroethane, edetate disodium, edetate sodium, fd&c yellow no. 6, fluorochlorohydrocarbons, gelatin, glycerin, glycine, hydrochloric acid, hydrochloric acid, diluted, lactose, lactose monohydrate, lecithin, lecithin, hydrogenated soy, lecithin, soybean, lysine monohydrate, mannitol, menthol, methylparaben, nitric acid, nitrogen, norflurane, oleic acid, polyethylene glycol 1000, povidone k25, propylene glycol, propylparaben, saccharin, saccharin sodium, silicon dioxide, colloidal, sodium bisulfate, sodium bisulfite, sodium chloride, sodium citrate, sodium hydroxide, sodium lauryl sulfate, sodium metabisulfite, sodium sulfate anhydrous, sodium sulfite, sorbitan trioleate, sulfuric acid, thymol, titanium dioxide, trichloromonofluoromethane, tromethamine and zinc oxide. A pharmaceutical composition for nasal administration may comprise at least one inactive ingredient. Any or none of the inactive ingredients used may have been approved by the US Food and Drug Administration (FDA). A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for nasal administration includes acetic acid, alcohol, dehydrated, allyl .alpha.-ionone, anhydrous dextrose, anhydrous trisodium citrate, benzalkonium chloride, benzethonium chloride, benzyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, caffeine, carbon dioxide, carboxymethylcellulose sodium, cellulose, microcrystalline, chlorobutanol, citric acid, citric acid monohydrate, dextrose, dichlorodifluoromethane, di chlorotetrafluoroethane, edetate disodium, glycerin, glycerol ester of hydrogenated rosin, hydrochloric acid, hypromellose 2910 (15000 mpa.s), methylcelluloses, methylparaben, nitrogen, norflurane, oleic acid, petrolatum, white, phenylethyl alcohol, polyethylene glycol 3350, polyethylene glycol 400, polyoxyl 400 stearate, polysorbate 20, polysorbate 80, potassium phosphate, monobasic, potassium sorbate, propylene glycol, propylparaben, sodium acetate, sodium chloride, sodium citrate, sodium hydroxide, sodium phosphate, sodium phosphate, dibasic, sodium phosphate, dibasic, anhydrous, sodium phosphate, dibasic, dihydrate, sodium phosphate, dibasic, dodecahydrate, sodium phosphate, dibasic, heptahydrate, sodium phosphate, monobasic, anhydrous, sodium phosphate, monobasic, dihydrate, sorbitan trioleate, sorbitol, sorbitol solution, sucralose, sulfuric acid, trichloromonofluoromethane and trisodium citrate dihydrate. Ophthalmic and Auricular (Otic) Administration A pharmaceutical composition may be prepared, packaged, and / or sold in a formulation suitable for delivery to and / or around the eye and / or delivery to the ear (e.g., auricular (otic) administration). Non-limiting examples of route of administration for delivery to and / or around the eye include retrobulbar, conjuctival, intracorneal, intraocular, intravitreal, ophthlamic and subconjuctiva. Such formulations may, for example, be in the form of eye drops or ear drops including, for example, a 0.1 / 1.0% (w / w) solution and / or suspension of the active ingredient in an aqueous or oily liquid excipient. Such drops may further comprise buffering agents, salts, and / or one or more other of any additional ingredients described herein. Other ophthalmically-administrable formulations which are useful include those which comprise the active ingredient in microcrystalline form and / or in a liposomal preparation. Ear drops and / or eye drops are contemplated as being within the scope of this invention. A multilayer thin film device may be prepared to contain a pharmaceutical composition for delivery to the eye and / or surrounding tissue. A pharmaceutical composition for ophthalmic administration may comprise at least one inactive ingredient. Any or none of the inactive ingredients used may have been approved by the US Food and Drug Administration (FDA). A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for ophthalmic administration includes acetic acid, alcohol, alcohol, dehydrated, alginic acid, amerchol-cab, ammonium hydroxide, anhydrous trisodium citrate, antipyrine, benzalkonium chloride, benzethonium chloride, benzododecinium bromide, boric acid, caffeine, calcium chloride, carbomer 1342, carbomer 934p, carbomer 940, carbomer homopolymer type b (allyl pentaerythritol crosslinked), carboxymethylcellulose sodium, castor oil, cetyl alcohol, chlorobutanol, chlorobutanol, anhydrous, cholesterol, citric acid, citric acid monohydrate, creatinine, diethanolamine, diethylhexyl phthalate, divinylbenzene styrene copolymer, edetate disodium, edetate disodium anhydrous, edetate sodium, ethylene vinyl acetate copolymer, gellan gum (low acyl), glycerin, glyceryl stearate, high density polyethylene, hydrocarbon gel, plasticized, hydrochloric acid, hydrochloric acid, diluted, hydroxyethyl cellulose, hydroxypropyl methylcellulose 2906, hypromellose 2910 (15000 mpa.s), hypromelloses, jelene, lanolin, lanolin alcohols, lanolin anhydrous, lanolin nonionic derivatives, lauralkonium chloride, lauroyl sarcosine, light mineral oil, magnesium chloride, mannitol, methylcellulose (4000 mpa.s), methylcelluloses, methylparaben, mineral oil, nitric acid, nitrogen, nonoxynol-9, octoxynol-40, octylphenol polymethylene, petrolatum, petrolatum, white, phenylethyl alcohol, phenylmercuric acetate, phenylmercuric nitrate, phosphoric acid, polidronium chloride, poloxamer 188, poloxamer 407, polycarbophil, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 8000, polyoxyethylene - poly oxypropylene 1800, polyoxyl 35 castor oil, polyoxyl 40 hydrogenated castor oil, polyoxyl 40 stearate, polypropylene glycol, polysorbate 20, polysorbate 60, polysorbate 80, polyvinyl alcohol, potassium acetate, potassium chloride, potassium phosphate, monobasic, potassium sorbate, povidone k29 / 32, povidone k30, povidone k90, povidones, propylene glycol, propylparaben, soda ash, sodium acetate, sodium bisulfate, sodium bisulfite, sodium borate, sodium borate decahydrate, sodium carbonate, sodium carbonate monohydrate, sodium chloride, sodium citrate, sodium hydroxide, sodium metabisulfite, sodium nitrate, sodium phosphate, sodium phosphate dihydrate, sodium phosphate, dibasic, sodium phosphate, dibasic, anhydrous, sodium phosphate, dibasic, dihydrate, sodium phosphate, dibasic, heptahydrate, sodium phosphate, monobasic, sodium phosphate, monobasic, anhydrous, sodium phosphate, monobasic, dihydrate, sodium phosphate, monobasic, monohydrate, sodium sulfate, sodium sulfate anhydrous, sodium sulfate decahydrate, sodium sulfite, sodium thiosulfate, sorbic acid, sorbitan monolaurate, sorbitol, sorbitol solution, stabilized oxychloro complex, sulfuric acid, thimerosal, titanium dioxide, tocophersolan, trisodium citrate dihydrate, triton 720, tromethamine, tyloxapol and zinc chloride. A pharmaceutical composition for retrobulbar administration may comprise at least one inactive ingredient. A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for retrobulbar administration includes hydrochloric acid and sodium hydroxide. A pharmaceutical composition for intraocular administration may comprise at least one inactive ingredient. A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for intraocular administration includes benzalkonium chloride, calcium chloride, citric acid monohydrate, hydrochloric acid, magnesium chloride, polyvinyl alcohol, potassium chloride, sodium acetate, sodium chloride, sodium citrate and sodium hydroxide. A pharmaceutical composition for intravitreal administration may comprise at least one inactive ingredient. A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for intravitreal administration includes calcium chloride, carboxymethylcellulose sodium, cellulose, microcrystalline, hyaluronate sodium, hydrochloric acid, magnesium chloride, magnesium stearate, polysorbate 80, polyvinyl alcohol, potassium chloride, sodium acetate, sodium bicarbonate, sodium carbonate, sodium chloride, sodium hydroxide, sodium phosphate dibasic heptahydrate, sodium phosphate monobasic monohydrate and trisodium citrate dehydrate. A pharmaceutical composition for subconjunctival administration may comprise at least one inactive ingredient. A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for subconjunctival administration includes benzyl alcohol, hydrochloric acid and sodium hydroxide. A pharmaceutical composition for auricular administration may comprise at least one inactive ingredient. A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for auricular administration includes acetic acid, aluminum acetate, aluminum sulfate anhydrous, benzalkonium chloride, benzethonium chloride, benzyl alcohol, boric acid, calcium carbonate, cetyl alcohol, chlorobutanol, chloroxylenol, citric acid, creatinine, cupric sulfate, cupric sulfate anhydrous, edetate disodium, edetic acid, glycerin, glyceryl stearate, hydrochloric acid, hydrocortisone, hydroxyethyl cellulose, isopropyl myristate, lactic acid, lecithin, hydrogenated, methylparaben, mineral oil, petrolatum, petrolatum, white, phenylethyl alcohol, polyoxyl 40 stearate, polyoxyl stearate, polysorbate 20, polysorbate 80, polyvinyl alcohol, potassium metabisulfite, potassium phosphate, monobasic, povidone k90f, povidones, propylene glycol, propylene glycol diacetate, propylparaben, sodium acetate, sodium bisulfite, sodium borate, sodium chloride, sodium citrate, sodium hydroxide, sodium phosphate, dibasic, anhydrous, sodium phosphate, dibasic, heptahydrate, sodium phosphate, monobasic, anhydrous, sodium sulfite, sulfuric acid and thimerosal. DOSING Provided herein are methods comprising administering a vaccine composition to a subject. The specific dose level for any particular subject will depend upon a variety of factors including the species, the activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex, and diet of the subject; the time of administration, route of administration, and rate of excretion of the specific compound employed; drugs used in combination or coincidental with the specific compound employed; and like factors well known in the arts. Compositions in accordance with the present disclosure are typically formulated in dosage unit form for ease of administration and uniformity of dosage. It will be understood, however, that the total daily usage of the compositions of the present disclosure may be decided by the attending administrator within the scope of sound judgment. In certain embodiments, compositions in accordance with the present disclosure may be administered at dosage levels sufficient to deliver from about 0.0001 mg / kg to about 100 mg / kg, from about 0.001 mg / kg to about 0.05 mg / kg, from about 0.005 mg / kg to about 0.05 mg / kg, from about 0.001 mg / kg to about 0.005 mg / kg, from about 0.05 mg / kg to about 0.5 mg / kg, from about 0.01 mg / kg to about 50 mg / kg, from about 0.1 mg / kg to about 40 mg / kg, from about 0.5 mg / kg to about 30 mg / kg, from about 0.01 mg / kg to about 10 mg / kg, from about 0.1 mg / kg to about 10 mg / kg, from about 1 mg / kg to about 25 mg / kg, from about 0.1 mg / kg to about 250 mg / kg, or any range in between or any value in between, of subject body weight per day, one or more times a day, to obtain the desired therapeutic, diagnostic, prophylactic, or imaging effect. In some embodiments, compositions in accordance with the present disclosure may be administered at dosage levels sufficient to deliver from about 0.001 mg to about 500 mg of polypeptide(s) and / or peptide(s), or any range in between or any value in between. In some embodiments, compositions may be administered at dosage levels sufficient to deliver from about 0.01 to about 50 mg, or any range in between or any value in between. For example, in some embodiments, the range may be between about 0.1 and about 5 mg, or any range in between or any value in between, e.g., between about 0.1 and about 2 mg, or any range in between or any value in between. The desired dosage may be delivered three times a day, two times a day, once a day, every other day, every third day, every week, every two weeks, every three weeks, or every four weeks. In certain embodiments, the desired dosage may be delivered using multiple administrations (e.g. , two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, twenty, thirty, forty, or more administrations). When multiple administrations are employed, split dosing regimens such as those described herein may be used. In some embodiments, an animal is administered with a prime (initial dose), followed by a boost (second dose) at least about 1, 1.5, 2, 2.5, 3, 3.5, or 4 weeks after the prime. In some embodiments, at least one additional dose is given after the boost, optionally after about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months after the boost. In some embodiments, the at least one additional dose is repeated every 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,21,22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months. In preferred embodiments, an animal is administered with a prime, followed by a boost about 2 or 3 weeks after the prime. In yet other preferred embodiments, an animal is administered with (a) a prime, (b) a boost about 2 or 3 weeks after the prime, and (c) at least one additional dose every 3, 4, 5, or 6 months. Each dose in the dosing schedule may comprise the same or different amount of the vaccine composition. According to the present disclosure, the compositions of the present disclosure may be administered in split- dose regimens. As used herein, a "split dose" is the division of single unit dose or total daily dose into two or more doses, e.g, two or more administrations of the single unit dose. As used herein, a "single unit dose" is a dose of any therapeutic administed in one dose / at one time / single route / single point of contact, i.e., single administration event. As used herein, a "total daily dose" is an amount given or prescribed in 24 hr period. It may be administered as a single unit dose. In some embodiments, the compositions of the present disclosure are administed to a subject in split doses. The compositions may be formulated in buffer only or in a formulation described herein. DOSAGE FORMS Vaccines, antibodies, milk, animal feed, agents (e.g., an agent that reduces methane production in a subject, a probiotic bacterial strain, etc.), or other compositions of the present disclosure may be formulated into a dosage form described herein, such as an intranasal, intratracheal, or injectable (e.g., intravenous, intraocular, intravitreal, intramuscular, intracardiac, intraperitoneal, subcutaneous). Liquid dosage forms Liquid dosage forms for parenteral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and / or elixirs. In addition to active ingredients, liquid dosage forms may comprise inert diluents commonly used in the art including, but not limited to, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. In certain embodiments for parenteral administration, compositions may be mixed with solubilizing agents such as CREMOPHOR®, alcohols, oils, modified oils, glycols, polysorbates, cyclodextrins, polymers, and / or combinations thereof. Injectable Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art and may include suitable dispersing agents, wetting agents, and / or suspending agents. Sterile injectable preparations may be sterile injectable solutions, suspensions, and / or emulsions in nontoxic parenterally acceptable diluents and / or solvents, for example, a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed include, but are not limited to, water, Ringer's solution, U.S. P., and isotonic sodium chloride solution. Sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. Fatty acids such as oleic acid can be used in the preparation of injectables. Injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, and / or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use. In order to prolong the effect of an active ingredient, it may be desirable to slow the absorption of the active ingredient from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the compositions then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered compositions may be accomplished by dissolving or suspending the compositions in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the compositions in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of compositions to polymer and the nature of the particular polymer employed, the rate of a compound release can be controlled. Examples of other biodegradable polymers include, but are not limited to, poly(orthoesters) and poly(anhydrides). Depot injectable formulations may be prepared by entrapping the compositions in liposomes or microemulsions which are compatible with body tissues. Pulmonary Formulation Formulations described herein as being useful for pulmonary delivery may also be used for intranasal delivery of a pharmaceutical composition. Another formulation suitable for intranasal administration may be a coarse powder comprising the active ingredient and having an average particle from about 0.2 pu] to 500 pup Such a formulation may be administered in the manner in which snuff is taken, i.e. by rapid inhalation through the nasal passage from a container of the powder held close to the nose. Formulations suitable for nasal administration may, for example, comprise from about as little as 0.1% (w / w) and as much as 100% (w / w) of active ingredient, and may comprise one or more of the additional ingredients described herein. A pharmaceutical composition may be prepared, packaged, and / or sold in a formulation suitable for buccal administration. Such formulations may, for example, be in the form of tablets and / or lozenges made using conventional methods, and may, for example, contain about 0.1% to 20% (w / w) active ingredient, where the balance may comprise an orally dissolvable and / or degradable composition and, optionally, one or more of the additional ingredients described herein. Alternately, formulations suitable for buccal administration may comprise a powder and / or an aerosolized and / or atomized solution and / or suspension comprising active ingredient. Such powdered, aerosolized, and / or aerosolized formulations, when dispersed, may have an average particle and / or droplet size in the range from about 0.1 nm to about 200 nm, and may further comprise one or more of any additional ingredients described herein. General considerations in the formulation and / or manufacture of pharmaceutical agents may be found, for example, in Remington: The Science and Practice of Pharmacy 21st ed., Lippincott Williams & Wilkins, 2005 (incorporated herein by reference in its entirety). Coatings or Shells Solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally comprise opacifying agents and can be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes. Solid compositions of a similar type may be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. MUL TI-DOSE AND REPEA T-DOSE ADMINISTRA TION In some embodiments, vaccines, antibodies, milk, animal feed, agents (e.g., an agent that reduces methane production in a subject, a probiotic bacterial strain, a small molecule inhibitor, etc.), or other compositions of the present disclosure may be administered in two or more doses (referred to herein as "multi-dose administration"). Such doses may comprise the same components or may comprise components not included in a previous dose. Such doses may comprise the same mass and / or volume of components or an altered mass and / or volume of components in comparison to a previous dose. In some embodiments, multi-dose administration may comprise repeat-dose administration. As used herein, the term "repeat-dose administration" refers to two or more doses administered consecutively or within a regimen of repeat doses comprising same or different components. In some embodiments, the repeat dose may comprise substantially the same components provided at substantially the same mass and / or volume. In other embodiments, the repeat dose may comprise different components (e.g., different adjuvant for a vaccine composition). ADJUVANT Adjuvants or immune potentiators, may also be administered with or in combination with one or more vaccine composition of the present disclosure. The term "adjuvant" refers to an agent that when administered in conjunction with or as part of a composition described herein augments, enhances, and / or boosts the immune response to a methanogen, but when the agent is administered alone does not generate an immune response. In some embodiments, the adjuvant generates an immune response to a methanogen and does not produce an allergy or other adverse reaction. Adjuvants can enhance an immune response by several mechanisms including, e.g., lymphocyte recruitment, stimulation of B and / or T cells, and stimulation of macrophages. In some embodiments, an adjuvant acts as a co-signal to prime T-cells and / or B- cells and / or NK cells as to the existence of the cell surface protein of a methanogen in a vaccine composition of the present disclosure. Advantages of adjuvants include the enhancement of the immunogenicity of antigens, modification of the nature of the immune response, the reduction of the antigen amount needed for a successful immunization, the reduction of the frequency of booster immunizations needed and an improved immune response in elderly and immunocompromised vaccinees. These may be co-administered by any route, e.g., intramusculary, subcutaneous, IV or intradermal injections. Adjuvants useful in the present invention may include, but are not limited to, natural or synthetic. They may be organic or inorganic. When a vaccine or immunogenic composition of the invention comprises adjuvants or is administered together with one or more adjuvants, the adjuvants that can be used include, but are not limited to, mineral salt adjuvants or mineral salt gel adjuvants, particulate adjuvants, microparticulate adjuvants, mucosal adjuvants, and immunostimulatory adjuvants. Examples of adjuvants include, but are not limited to, aluminum salts (alum) (such as aluminum hydroxide, aluminum phosphate, and aluminum sulfate), 3 De-O-acylated monophosphoryl lipid A (MPL) (see GB 2220211), MF59 (Novartis), AS03 (Glaxo SmithKline), AS04 (Glaxo SmithKline), polysorbate 80 (Tween 80; ICL Americas, Inc.), imidazopyridine compounds (see International Application No. PCT / US2007 / 064857, published as International Publication No. WO2007 / 109812), imidazoquinoxaline compounds (see International Application No. PCT / US2007 / 064858, published as International Publication No. WO2007 / 109813) and saponins, such as QS21 (see Kensil et al, in Vaccine Design: The Subunit and Adjuvant Approach (eds. Powell & Newman, Plenum Press, NY, 1995); U.S. Pat. No. 5,057,540). In some embodiments, the adjuvant is Freund's adjuvant (complete or incomplete). Other adjuvants are oil in water emulsions (such as squalene or peanut oil), optionally in combination with immune stimulants, such as monophosphoryl lipid A (see Stoute et al, N. Engl. J. Med. 336, 86-91 (1997)). Aduvants may be selected from any of the classes (1) mineral salts, e.g., aluminium hydroxide and aluminium or calcium phosphate gels; (2) emulsions including: oil emulsions and surfactant based formulations, e.g., microfluidised detergent stabilised oil-in-water emulsion, purified saponin, oil-in- water emulsion, stabilised water-in-oil emulsion; (3) particulate adjuvants, e.g., virosomes (unilamellar liposomal vehicles incorporating influenza haemagglutinin), structured complex of saponins and lipids, polylactide co-glycolide (PLG); (4) microbial derivatives; (5) endogenous human immunomodulators; and / or (6) inert vehicles, such as gold particles; (7) microorganism derived adjuvants; (8) tensoactive compunds; (9) carbohydrates; or combinations thereof. Other adjuvants which may be utilized in the vaccines of the present disclosure include any of those listed on the web-based vaccine adjuvant database, Vaxjo; World Wide Web at violinet.org / vaxjo / and described in for example Sayers, et al., J. Biomedicine and Biotechnology, volume 2012 (2012), Article ID 831486, 13 pages, the content of which is incorporated herein by reference in its entirety. Selection of appropriate adjuvants will be evident to one of ordinary skill in the art. Specific adjuvants may include,without limitation, cationic liposome-DNA complex JVRS-100, aluminum hydroxide vaccine adjuvant, aluminum phosphate vaccine adjuvant, aluminum potassium sulfate adjuvant, alhydrogel, ISCOM(s)™, Freund's complete adjuvant, Freund's incomplete adjuvant, CpG DNA Vaccine Adjuvant, Cholera toxin, Cholera toxin B subunit, Liposomes, Saponin Vaccine Adjuvant, DDA Adjuvant, Squalene-based Adjuvants, Etx B subunit Adjuvant, IL-12 Vaccine Adjuvant, LTK63 Vaccine Mutant Adjuvant, TiterMax Gold Adjuvant, Ribi Vaccine Adjuvant, Montanide ISA 720 Adjuvant, Corynebacterium-derb / ed P40 Vaccine Adjuvant, MPL™ Adjuvant, AS04, AS02, Lipopolysaccharide Vaccine Adjuvant, Muramyl Dipeptide Adjuvant, CRL1005, Killed Corynebacterium parvum Vaccine Adjuvant, Montanide ISA 51, Bordetella pertussis component Vaccine Adjuvant, Cationic Liposomal Vaccine Adjuvant, Adamantylamide Dipeptide Vaccine Adjuvant, Arlacel A, VSA-3 Adjuvant, Aluminum vaccine adjuvant, Polygen Vaccine Adjuvant, Adjumer™, Algal Glucan, Bay RI005, Theramide®, Stearyl Tyrosine, Specol, Algammulin, Avridine®, Calcium Phosphate Gel, CTA1-DD gene fusion protein, DOC / Alum Complex, Gamma Inulin, Gerbu Adjuvant, GM-CSF, GMDP, Recombinant hlFN-gamma / Interferon-g, Interleukin-ip, Interleukin-2, Interleukin-7, Sclavo peptide, Rehydragel LV, Rehydragel HP A, Loxoribine, MF59, MTP-PE Liposomes, Murametide, Murapalmitine, D-Murapalmitine, NAGO, Non- Ionic Surfactant Vesicles, PMMA, Protein Cochleates, QS-21, SPT (Antigen Formulation), nanoemulsion vaccine adjuvant, AS03, Quil-A vaccine adjuvant, RC529 vaccine adjuvant, LTR192G Vaccine Adjuvant, E. coli heat-labile toxin, LT, amorphous aluminum hydroxyphosphate sulfate adjuvant, Calcium phosphate vaccine adjuvant, Montanide Incomplete Seppic Adjuvant, Imiquimod, Resiquimod, AF03, Flagellin, Poly(LC), ISCOMATRIX®, Abisco-100 vaccine adjuvant, Albumin- heparin microparticles vaccine adjuvant, AS-2 vaccine adjuvant, B7-2 vaccine adjuvant, DHEA vaccine adjuvant, Immunoliposomes Containing Antibodies to Costimulatory Molecules, SAF-1, Sendai Proteoliposomes, Sendai-containing Lipid Matrices, Threonyl muramyl dipeptide (TMDP), Ty Particles vaccine adjuvant, Bupivacaine vaccine adjuvant, DL-PGL (Polyester poly (DL-lactide-co-glycolide)) vaccine adjuvant, IL-15 vaccine adjuvant, LTK72 vaccine adjuvant, MPL-SE vaccine adjuvant, non-toxic mutant El 12K of Cholera Toxin mCT-El 12K, and / or Matrix-S. In some embodiments, the at least one adjuvant comprises oil emulsions, e.g., comprising at least (a) mineral oil lipid and (b) aqueous phase (e.g., Freund’s complete adjuvant, Freund’s incomplete adjuvant, Montanide ISA series (e.g., ISA70, ISA61, ISA206, ISA50), squaline-based emulsion, (e.g., MF59 and / or AS03), saponins, (e.g., Quil-A, Spikoside, QS21, or ISCOMs, e.g., ISCOPREP 703), aluminum salts (e.g., aluminum hydroxide, aluminum phosphate, and potassium aluminum sulfate), also known to a skilled artisan as ‘alum’, (e.g., Imject Alum), dextran sulfate, chitosan thermogel, (e.g., monophosphoryl lipid A), Carbol, PLGA, MDP, CpG ODN, cytokine-based adjuvants such as IL-12 and / or GM-CSF, a lipid nanoparticle / cationic liposome adjuvant, an immune stimulating complex, or any combination of two or more thereof. In preferred embodiments, the at least one adjuvant comprises Freund’s complete adjuvant and / or Freund’s incomplete adjuvant. See Spickler and Roth (2003) J Vet Intern Med, 17:273-281, which is incorporated herein by reference. In some embodiments, the at least one adjuvant comprises Emulsigen-D, Emulsigen, Emulsigen-P, and / or Polygen (MVP adjuvant, Omaha, NE). In some embodiments, the at least one adjuvant comprises ENABL 06 (HuvePharma, Peachtree City, GA). In some embodiments, the at least one adjuvant comprises Montainde ISA 201 and / or Montanide Gel 02 (Seppic Inc., New Jersey). Other adjuvants which may be co-administered with the vaccine compositions of the invention include, but are not limited to interferons, TNF-alpha, TNF-beta, chemokines such as CCL21, eotaxin, HMGB1, SA100-8alpha, GCSF, GMCSF, granulysin, lactoferrin, ovalbumin, CD-40L, CD28 agonists, PD-1, soluble PD1, LI or L2, or interleukins such as IL-1, IL-2, IL-4, IL-6, IL-7, IL-10, IL-12, IL-13, IL-21, IL-23, IL-15, IL-17, and IL-18. In some embodiments, the adjuvant comprises Glucopyranosyl Lipid Adjuvant (GLA), CpG oligodeoxynucleotides (e.g., Class A or B), poly(LC), aluminum hydroxide, or Pam3CSK4. In some embodiments, the adjuvant comprises: (a) (±)-N-(3-aminopropyl)-N,N-dimethyl-2,3-bis(syn-9-tetradeceneyloxy)-l-propanaminium bromide (GAP-DMORIE) and a neutral lipid; (b) a cytokine; (c) mono-phosphoryl lipid A and trehalosedicorynomycolateAF (MPL+TDM); (d) a solubilized mono-phosphoryl lipid A formulation; and / or (e) CRL1005 / BAK. In some embodiments, the neutral lipid in (a) comprises (a) l,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE); (b) l,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DPyPE); and / or (c) l,2-dimyristoyl-glycer-3-phosphoethanolamine (DMPE). In some embodiments, the adjuvant comprises saponin, Montanide ISA61, a chitosan thermogel, a lipid nanoparticle / cationic liposome adjuvant, or any combination thereof. In preferred embodiments, the adjuvant comprises Montanide ISA61. ANTIBODY Unless otherwise specified here within, the terms “antibody” and “antibodies” broadly encompass naturally-occurring forms of antibodies (e.g. IgG, IgA, IgM, IgE); and recombinant antibodies, such as single-chain antibodies, chimeric antibodies, and multi-specific antibodies, as well as fragments and derivatives of all of the foregoing, which fragments and derivatives have at least an antigenic binding site. Antibody derivatives may comprise a protein or chemical moiety conjugated to an antibody. The term “antibody” as used herein also includes an “antigen-binding portion” of an antibody (or simply “antibody portion”). The term “antigen-binding portion”, as used herein, refers to one or more fragments of an antibody that retain the ability to specifically bind to an antigen (e.g., at least one cell surface protein or fragment thereof of at least one methanogen). It has been shown that the antigen-binding function of an antibody can be performed by fragments of a full-length antibody. Examples of binding fragments encompassed within the term “antigenbinding portion” of an antibody include (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CHI domains; (ii) a F(ab')2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment consisting of the VH and CHI domains; (iv) a Fv fragment consisting of the VL and VH domains of a single arm of an antibody, (v) a dAb fragment (Ward et aL, (1989) Nature 341:544-546), which consists of a VH domain; and (vi) an isolated complementarity determining region (CDR). Furthermore, although the two domains of the Fv fragment, VL and VH, are coded for by separate genes, they can be joined, using recombinant methods, by a synthetic linker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent polypeptides (known as single chain Fv (scFv); see e.g., Bird et al. (1988) Science 242:423-426; and Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883; and Osbourn et al. 1998, Nature Biotechnology 16: 778). Such single chain antibodies are also intended to be encompassed within the term “antigen-binding portion” of an antibody. Any VH and VL sequences of specific scFv can be linked to immunoglobulin constant region cDNA or genomic sequences, in order to generate expression vectors encoding complete IgG polypeptides or other isotypes (e.g., IgGA). VH and VL can also be used in the generation of Fab, Fv or other fragments of immunoglobulins using either protein chemistry or recombinant DNA technology. Other forms of single chain antibodies, such as diabodies are also encompassed. Diabodies are bivalent, bispecific antibodies in which VH and VL domains are expressed on a single polypeptide chain, but using a linker that is too short to allow for pairing between the two domains on the same chain, thereby forcing the domains to pair with complementary domains of another chain and creating two antigen binding sites (see e.g., Holliger et al. (1993) Proc. Natl. Acad. Sci. U.S.A. 90:6444-6448; Poljak et al. (1994) Structure 2:1121-1123). Still further, an antibody or antigen-binding portion thereof may be part of larger immunoadhesion polypeptides, formed by covalent or noncovalent association of the antibody or antibody portion with one or more other proteins or peptides. Examples of such immunoadhesion polypeptides include use of the streptavidin core region to make a tetrameric scFv polypeptide (Kipriyanov et al. (1995) Human Antibodies andHybridomas 6:93-101) and use of a cysteine residue, biomarker peptide and a C-terminal polyhistidine tag to make bivalent and biotinylated scFv polypeptides (Kipriyanov et al. (1994) Mo / . Immunol. 31:1047-1058). Antibody portions, such as Fab and F(ab')2 fragments, can be prepared from whole antibodies using conventional techniques, such as papain or pepsin digestion, respectively, of whole antibodies. Moreover, antibodies, antibody portions and immunoadhesion polypeptides can be obtained using standard recombinant DNA techniques, as described herein. Antibodies may be polyclonal or monoclonal; xenogeneic, allogeneic, or syngeneic; or modified forms thereof (e.g. chimeric, etc.}. Antibodies may also be fully specific to the subject, e.g., the antibodies may be fully ruminant or fully human. The terms “monoclonal antibodies” and “monoclonal antibody composition,” as used herein, refer to a population of antibody polypeptides that contain only one species of an antigen binding site capable of immunoreacting with a particular epitope of an antigen, whereas the term “polyclonal antibodies” and “polyclonal antibody composition” refer to a population of antibody polypeptides that contain multiple species of antigen binding sites capable of interacting with a particular antigen. A monoclonal antibody composition typically displays a single binding affinity for a particular antigen with which it immunoreacts. The present disclosure includes a monoclonal antibody that works particularly well in binding and neutralizing at least one methanogen. Upon immunizing a subject population (e.g., of milk-producing subject), the milk comprising the antibody can be screened for antibodies with superior activity (e.g., specific binding, neutralizing at least one methanogen, etc.). The amino acid sequence of such antibodies can be determined (e.g., mass spec-based sequencing, Next Gen Sequencing, or other methods known in the art), their expressing DNA vectors can be synthesized, and monoclonal antibodies can be produced. One or a combination of at least two or more antibodies can be added to the drinking water and / or animal feed, and be given to a subject population. Alternatively, such monoclonal antibodies can be generated by immunizing a vehicle animal (e.g., mouse, rabbit, etc.), and hybridomas expressing the animals can be recovered. Standard hybridoma methods for producing antibodies are described in, e.g., Harlow and Lane (eds.), Antibodies: A Laboratory Manual, CSH Press (1988), and CA. Janeway et al. (eds.), Immunobiology, 5th Ed., Garland Publishing, New York, NY (2001)). Antibodies produced by hybridomas can be screened and utilized according to the methods described above and herein. In some embodiments, the antibody is a polyclonal antibody. In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody is an IgG or IgA. In some embodiments, the antibody is IgA. The IgA isoform, at least in cattle, may be more stable in the rumen. For example, IgA levels in cattle saliva were reduced by only 40% after 8h exposure to rumen contents while IgG levels were reduced by 80%. In some embodiments, the antibody is lyophilized. In some embodiments, the antibody is in a pharmaceutical composition of the present disclosure or those known in the art. In some embodiments, a composition comprising an antibody further comprises at least one excipient and / or carrier. In some embodiments, the antibody is in the animal feed. In some embodiments, the antibody is in the solid animal feed. In other embodiments, the antibody is in the liquid animal feed. In some embodiments, the antibody is in the drinking water or milk. In preferred embodiments, the antibody is orally consumed by a subject such that the antibody comes in contact with at least one methanogen present in the gut of the subject. In preferred embodiments, oral administration of the antibody reduces the number and / or type of at least one methanogen. METHODS FOR DETECTION OF ANTIBODY In certain embodiments, an efficacious vaccine produces an antibody titer of greater than 1:40, greater that 1:100, greater than 1:400, greater than 1:1000, greater than 1:2000, greater than 1:3000, greater than 1:4000, greater than 1:500, greater than 1:6000, greater than 1:7500, greater than 1:10000. In some embodiments, the antibody titer is produced or reached by 10 days following vaccination, by 20 days following vaccination, by 30 days following vaccination, by 40 days following vaccination, or by 50 or more days following vaccination. In some embodiments, the titer is produced or reached following a single dose of vaccine administered to the subject. In other embodiments, the titer is produced or reached following multiple doses, e.g., following a first and a second dose (e.g., a repeat dose.). In certain aspects, antigen-specific antibodies are measured in units of pg / ml or are measured in units of IU / L (International Units per liter) or mIU / ml (milli International Units per ml). In some embodiments of the invention, an efficacious vaccine produces >0.5 pg / ml, >0.1 pg / ml, >0.2 pg / ml, >0.35 pg / ml, >0.5 pg / ml, >1 pg / ml, >2 pg / ml, >5 pg / ml or >10 pg / ml. In some embodiments, an efficacious vaccine produces >10 mIU / ml, >20 mIU / ml, >50 mIU / ml, >100 mIU / ml, >200 mIU / ml, >500 mIU / ml or > 1000 mIU / ml. Methods of detecting the presence of antibodies are well known in the art. In some embodiments, antibody level or concentration is determined or measured by neutralization assay, e.g., neutralization of at least one methanogen. Other exemplary methods include, but are not limited to, immunodiffusion, immunoelectrophoresis, radioimmunoassay (RIA), enzyme-linked immunosorbent assays (ELISAs; including variants such as competitive ELISA, sandwich ELISA, etc.), immunofluorescent assays, Western blotting, immunohistochemical techniques, agglutination, complement assays, high performance liquid chromatography (HPLC), thin layer chromatography (TLC), hyperdiffusion chromatography, and the like (e.g., Basic and Clinical Immunology, Sites and Terr, eds., Appleton and Lange, Norwalk, Conn, pp 217-262, 1991 which is incorporated by reference). For example, ELISA and RIA procedures may be conducted such that a desired protein standard (e.g., an extracellular domain of at least one cell surface protein or a fragment thereof of at least one methanogen) is labeled (with a radioisotope such as 125I or 35S, or an assayable enzyme, such as horseradish peroxidase or alkaline phosphatase), and is brought into contact with a sample comprising the antibody, whereon the amount of the labeled protein standard bound to the antibody is measured. Enzymatic and radiolabeling of a protein and / or the antibodies may be effected by conventional means. Such means will generally include covalent linking of the enzyme to the antigen or the antibody in question, such as by glutaraldehyde, specifically so as not to adversely affect the activity of the enzyme, by which is meant that the enzyme must still be capable of interacting with its substrate, although it is not necessary for all of the enzyme to be active, provided that enough remains active to permit the assay to be effected. Indeed, some techniques for binding enzymes are non-specific (such as using formaldehyde), and will only yield a proportion of active enzyme. It may be desirable to immobilize one component of the assay system on a support, thereby allowing other components of the system to be brought into contact with the component and readily removed without laborious and time-consuming labor. It is possible for a second phase to be immobilized away from the first, but one phase is usually sufficient. It is possible to immobilize the enzyme itself on a support, but if solid-phase enzyme is required, then this is generally best achieved by binding to antibody and affixing the antibody to a support, models and systems for which are well-known in the art. Simple polyethylene may provide a suitable support. Enzymes employable for labeling are not particularly limited, but may be selected from the members of the oxidase group, for example. These catalyze production of hydrogen peroxide by reaction with their substrates, and glucose oxidase is often used for its good stability, ease of availability and cheapness, as well as the ready availability of its substrate (glucose). Activity of the oxidase may be assayed by measuring the concentration of hydrogen peroxide formed after reaction of the enzyme-labeled antibody with the substrate under controlled conditions well-known in the art. MILK In certain aspects, provided herein are milk and derivatives thereof. Milk produced by vaccinated female subjects (e.g., dairy cows) comprises antibodies that bind at least one cell surface protein or a fragment thereof of at least one methanogen. Such milk can be orally consumed by subjects such that the antibodies therein can come in contact with at least one methanogen present in the gut of the subjects. Upon contact, the antibodies in the milk can neutralize the at least one methanogen and contribute to reducing methane production by the subjects. Thus, milk from vaccinated female subject can be used to treat breast-feeding animals, thereby reducing methane production and / or methanogen colonization in young animals. This can be especially important when vaccination of young animals occurs concurrently with weaning. In some embodiments, the milk is pasteurized and / or homogenized. In some emdobiments, the milk is lyophilized, filtered, concentrated, evaporated, or processed to form dry milk powder (e.g., boiling at low pressure at low temperature). In some embodiments, said processing may allow longer shelf life of the milk / milk product and the antibodies present therein. In some embodiments, the fat content is removed / reduced from the milk. Processing of milk and / or preparation of derivatives of milk are well known in the art. Appropriate care is taken to preserve the structural and functional (e.g., binding a methanogen) aspects of the antibodies. For example, in some embodiments, high pressure (-200 MPa) and low temperature (-4°C) are used throughout the process as described at least by Kim et al. (2008) Journal of Dairy Science, 91:4176-4182. In other embodiments, milk may be pasteurized at low-termperature of 60 °C for 10 minutes at standard pressure. These conditions may pasteurize milk without significantly altering the antibody function. Alternatively, milk can be filtered to remove microorganisms instead of pasteurizing. Microfiltration is a process that replaces pasteurization and produces milk with fewer microorganisms and longer shelflife without a change in the quality of the milk. In this process, cream is separated from the skimmed milk and the skimmed milk is forced through ceramic microfilters that trap 99.9% of microorganisms in the milk (as compared to 99.999% killing of microorganisms in standard high temperature short time pasteurization). Ultrafiltration uses finer filters than microfiltration, which allow lactose and water to pass through while retaining fats, calcium and protein. As with microfiltration, the fat may be removed before filtration and added back in afterwards. Ultrafiltered milk is used widely in the industry in cheesemaking. Colostrum may similarly be used in the milk embodiments disclosed herein. ANIMAL FEED Provided herein are animal feeds that are useful in reducing methane production by a subject. Animal feed encompasses any edible consumables that are suitable for consumption by the subject of the present disclosure. Accordingly, animal feed also includes drinking water or other food items that may be consumed by the subject including but not limited to humans, canines, felines, and ruminants. Animal feed may be used in combination with or comprise any one of vaccines, antibodies, milk, agents (e.g., an agent that reduces methane production in a subject, a probiotic bacterial strain, a small molecule inhibitor, etc.), or other compositions of the present disclosure (e.g., those reducing methane production in a subject). Animal feed may comprise at least one agent, which reduces the methane production in a subject. In some embodiments, the animal feed comprises an antibody that binds at least one cell surface antigen or a fragment thereof of at least one methanogen. In some embodiments, the animal feed comprises a composition comprising an antibody that binds at least one cell surface antigen or a fragment thereof of at least one methanogen. For example, the animal feed may comprise milk or derivatives thereof comprising said antibody. In some embodiments, the animal feed is liquid (e.g., drinking water, milk). An antibody that binds at least one cell surface antigen or a fragment thereof of at least one methanogen or a composition comprising same may be added to the liquid animal feed (e.g., drinking water) before being given to the subject. In some embodiments, said antibody or a composition comprising same may be added to the drinking water. In other embodimetns, the milk or derivatives thereof comprising said antibody may be given directly to the subject, or added to other liquid animal feed (e.g., drinking water). In other embodiments, the animal feed is solid. In some such embodiments, the animal feed may comprise hay, straw, silage, compressed and pelleted feeds, oils and mixed rations, and sprouted grains and legumes. An antibody that binds at least one cell surface antigen or a fragment thereof of at least one methanogen or a composition comprising same may be added to the solid animal feed before being given to the subject. In some embodiments, an animal feed may comprise fats and fatty acids that further aid in reducing methane production in subjects. Based on a meta-analysis, fat supplementation reduced CH4 by 3.77% in cattle and 4.30% in sheep per 1% dietary fats. Fat decreases CH4 production (expressed as g / kg digestible dry matter (DM)) more from sheep than from cattle, which was attributed to the comparatively lower depression of DM digestion together with numerically larger depression of CH4 production (g / kg DM) by fat in sheep. Among fatty acids, C12:0, C18:3 and other polyunsaturated fatty acids (PUFA) are more potent than saturated fatty acids. The CH4-suppressing efficacy of fats generally pers...
Claims
1. A vaccine composition comprising at least one polypeptide and / or at least one peptide ofat least one cell surface protein or a fragment thereof of at least one methanogen.
2. The vaccine composition of claim 1, wherein(a) the at least one methanogen is of a family Melhanobacleriaceae:(b) the at least one methanogen is of a genus selected from: Methanobrevibacter, Methanosphaera, Methanomicrobium, Methanobacterium, Methanocorpusulum, Methanosaeta, Methanoculleus, Methanosarcina, and Thermoplasmatales, optionally Methanobrevibacter, Methanomicrobium, and Methanosarcina, and / or(c) the at least one methanogen comprises Methanobacterium formicicum, Methanobacterium bryantii, Methanobrevibacter ruminantium, Methanobrevibacter millerae, Methanobrevibacter olleyae, Methanomicrobium mobile, Methanoculleus olentangyi, Methanosarcina barkeri, Methanobrevibacter boviskoreani, Methanobacterium beijingense, Methanoculleus marisnigri, Methanoculleus bourgensis, Methanosarcina mazei, Thermoplasmatales archaeon BRNA1, Methanobrevibacter gottschalkii, Methanobrevibacter thaueri, Methanobrevibacter smithii, Methanosphaera stadtmanae, Methanococcoides burtonii, Methanolobus psychrophilus RI5, Methanobacterium paludism, Methanohalobium evestigatum, Methanomethylovorans hollandica, Methanothrix soehngenii, Methanocaldococcus vulcanius, Methanosalsum zhilinae, Methanocorpusculum labreanum, Methanoregula formicica, Methanoculleus marisnigri, Methanocella arvoryzae, Methanoculleus bourgensis, Methanolacinia petrolearia, Methanospirillum hungatei, Methanoplanus limicola, Methanohalophilus mahii, Methanococcus aeolicus, Methanosphaerula palustris, Methanocaldococcus fervens, Methanocaldococcus jannaschii, Methanocaldococcus sp. FS406-22, Methanoregula boonei, Methanobrevibacter sp. AbM4, Methanobrevibacter ruminantium, Methanosphaera, Methanobacterium formicicum, Methanocaldococcus villosus, Methanosarcina barkeri, Methanobacterium lacus, Methanotorris igneus, Methanotorris formicicus, Methanocaldococcus infernus, Methanofollis liminatans, Methanothermococcus okinawensis, Methanobrevibacter smithii, Methanobrevibacter, Methanocella conradii, Methanothermococcus thermolithotrophicus, Methanococcus maripaludis, Methanococcus maripaludis, Methanococcus vannielii, Methanothermus fervidus, Methanosarcina acetivorans, Methanosarcina mazei, Methanosaeta harundinacea 6Ac, Methanococcus maripaludis, Methanococcus voltae, Methanolinea tarda, Methanolobus psychrophilus, Methanosaeta harundinacea, or any combination thereof3. The vaccine composition of claim 1 or 2, wherein the at least one methanogen comprises Methanobrevibacter gottschalkii and / or Methanobrevibacter ruminantium.
4. The vaccine composition of any one of claims 1-3, wherein the vaccine composition comprises at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 polypeptides and / or peptides.
5. The vaccine composition of claim 4, wherein the at least two polypeptides and / or peptides are of the same cell surface protein or of different cell surface proteins.
6. The vaccine composition of any one of claims 1-5, wherein the at least one cell surface protein or a fragment thereof comprises at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97% 98%, 99%, or 100% sequence identity to an amino acid sequence of the present disclosure, optionally wherein the at least one cell surface protein or a fragment thereof comprises at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97% 98%, 99%, or 100% sequence identity to an amino acid sequence set forth in any one of Tables C-F, 1A, IB, 2A, 2B, 3 A, 3B, 4A, 4B, 5 A, 5B, and 6A-6G, or a fragment thereof.
7. The vaccine composition of any one of claims 1-6, wherein the at least one cell surface protein or a fragment thereof comprises at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97% 98%, 99%, or 100% sequence identity to an amino acid sequence encoded by at least one nucleic acid of the present disclosure, optionally wherein the at least one nucleic acid comprises the nucleotide sequence set forth in any one of Tables C-F, 1A, IB, 2A, 2B, 3 A, 3B, 4A, 4B, 5A, 5B, and 6A-6G, or a fragment thereof.
8. The vaccine composition of any one of claims 1-7, wherein the vaccine composition comprises at least one full-length protein of at least one cell surface protein.
9. The vaccine composition of any one of claims 1-7, wherein the vaccine composition comprises at least one fragment of at least one cell surface protein, optionally wherein the fragment is a polypeptide or a peptide.
10. The vaccine composition of claim 9, wherein the at least one fragment:(a) comprises an extracellular domain or a portion thereof;(b) lacks a signal peptide, optionally a native signal peptide; and / or(c) lacks a transmembrane domain, optionally a native transmembrane domain.
11. The vaccine composition of claim 9 or 10, wherein the at least one fragment lacks at least, about, or no more than 1, 5, 10, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, or 100 amino acids, optionally from the N-terminus and / or the C-terminus.
12. The vaccine composition of any one of claims 1-11, wherein the at least one cell surface protein or a fragment thereof comprises an adhesin-like protein; adhesin-like protein with cysteine protease domain; tetrahydromethanopterin S-methyltransferase subunit; ATP-processing protein; cell wall biosynthesis protein; cofactor biosynthesis protein; CRISPR protein; energy metabolism protein; enzyme; fatty acid synthesis protein; general metabolism protein; membrane protein; metal-binding protein; methanogenesis protein; Mtr protein; MtrE protein; phage-related protein; proteolysis protein; transcription regulation protein; ribosomal protein; substrate binding protein; transcription protein; transport protein; protein whose expression changes in response to lauric acid stress; a fragment thereof; and / or any combination thereof (optionally those listed in e.g., Table 6G).
13. The vaccine composition of any one of claims 1-12, wherein the at least one polypeptide and / or at least one peptide is formulated in lipid or saline.
14. The vaccine composition of any one of claims 1-13, wherein in the vaccine composition is a pharmaceutical composition, optionally comprising at least one carrier and / or at least one excipient.
15. The vaccine composition of any one of claims 1-14, wherein the vaccine composition comprises about 0.01 mg to about 50 mg of protein per mL, optionally about 0.1 mg to about 5 mg of protein per mL.
16. The vaccine composition of any one of claims 1-15, wherein the vaccine composition comprises about 0.01 mg to about 50 mg of protein, optionally about 0.1 mg to about 5 mg of protein.
17. The vaccine composition of any one of claims 1-16, wherein the at least one polypeptide and / or at least one peptide is lyophilized.
18. The vaccine composition of any one of claims 1-16, wherein the at least one polypeptide and / or at least one peptide is in a liquid composition.
19. The vaccine composition of any one of claims 1-18, wherein the vaccine composition comprises at least one adjuvant.
20. The vaccine composition of claim 19, wherein the at least one adjuvant comprises:(a) inorganic salts, preferably aluminum and calcium salts;(b) an oil emulsion;(c) saponins;(d) lipid or liposomes(e) an immune-stimulating complex;(f) a carrier protein (e.g., KLH, optionally conjugated to the at least one polypeptide and / or at least one peptide);(g) a bacterial product or derivatives thereof (e.g., bacterial toxinis, lipopolysaccharide, etc.);(h) a cytokine; or(i) any combination of two or more selected from (a)-(h).
21. The vaccine composition of claim 19 or 20, wherein the at least one adjuvant comprises Complete Freund’s adjuvant, Incomplete Freund’s adjuvant, Montanide ISA70, Montanide ISA61, Saponin, chitosan thermogel, lipid (e.g., monophosphoryl lipid A), a lipid nanoparticle / cationic liposome adjuvant, Emulsigen-D, Emulsigen, Emulsigen-P, Polygen, ENABL 06, Montainde ISA 201, Montanide Gel 02, or any combination of two or more thereof.
22. The vaccine composition of any one of claims 1-21, wherein the vaccine composition induces immune response against at least one cell surface protein or a fragment thereof of the at least one methanogen.
23. A method of treating a disease in a subject, the method comprising administering to the subject a vaccine composition of any one of claims 1-22.
24. The method of claim 23, wherein the disease is a periodontal disease, Inflammatory Bowel Disease (IBD), irritable bowel syndrome (ISB), ISB-C, small instestinal bacterialovergrowth (SIBO), colorectal cancer, obesity, metabolic syndrome, diverticulosis and diverticulitis, liver abscess, gingivitis, and / or bloat.
25. The method of claim 23 or 24, wherein the disease is associated with elevated, increased, or severe lactic acidosis.
26. A method of inducing an immune response against at least one methanogen in a subject, the method comprising administering to the subject the vaccine of any one of claims 1-22.
27. The method of claim 26, wherein the immune response comprises a B cell response and / or a T cell response, preferably a B cell response.
28. A method of reducing rumen lactate, increasing pH, or combination thereof in a subject, the method comprising administering to the subject the vaccine of any one of claims 1-22.
29. A method of reducing the activity, number, and / or type of methanogens in a digestive tract of a subject, the method comprising administering to the subject the vaccine composition of any one of claims 1-22.
30. The method of claim 29, wherein the digestive track comprises rumen, reticulum, omasum, abomasum, small intestine, and / or large intestine, preferably rumen.
31. A method of reducing the amount of methane (CH4) and / or hydrogen (H2) emitted by a subject, preferably eructated and / or exhaled, the method comprising administering to the subject the vaccine composition of any one of claims 1-22.
32. The method of claim 31, wherein the amount of methane (CH4) and / or hydrogen (H2) is reduced by about 5-100%, preferably by about 10-100%, compared to a control, optionally wherein the amount of methane (CH4) and / or hydrogen (H2) is reduced by at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% compared to a control.
33. The method of claim 31 or 32, wherein the amount of methane (CH4) and / or hydrogen (H2) is reduced by about 20-100%, preferably by about 30-100%, compared to a control.
34. The method of any one of claims 31-33, wherein the amount of methane (CH4) isreduced by (a) about 1 kg - about 50 kg within 8 weeks from the time of first vaccination, or (b) about 5 kg - about 300 kg within a year from the time of first vaccination, compared to a control.
35. The method of any one of claims 31-34, wherein the amount of methane (CH4)normalized to an amount of CO2 emitted by the subject (i.e., CH4 / CO2) is reduced by about 5100%, preferably by about 10-100%, compared to a control, optionally wherein the amount of methane (CH4) normalized to the amount of CO2 is reduced by at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% compared to a control.
36. The method of claim 35, wherein the amount of methane (CH4) normalized to theamount of CO2 is reduced by about 20-100%, preferably by about 30-100%, compared to a control.
37. The method of any one of claims 31-36, wherein the amount of hydrogen (H2) is reduced by (a) about 10 g- about 500 g within 8 weeks from the time of first vaccination, or (b) about 50 g - about 3 kg within a year from the time of first vaccination, compared to a control.
38. A method of increasing the amount of carbon dioxide (CO2) emitted by a subject, preferably eructated and / or exhaled, the method comprising administering to the subject the vaccine composition of any one of claims 1-22.
39. The method of claim 38, wherein the amount of carbon dioxide (CO2) is increased byabout 1-100%, preferably by about 1-20%, compared to a control, optionally wherein the amount of CO2 is increased by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% compared to a control.
40. The method of claim 38 or 39, wherein the amount of carbon dioxide (CO2) is increased by about 3-10%, preferably by about 3-20%, compared to a control.
41. The method of any one of claims 38-40, wherein the amount of carbon dioxide (CO2) isincreased by (a) about 29.8 kg - about 1,490 kg within 8 weeks from the time of firstvaccination, or (b) about 149 kg - about 8,940 kg within a year from the time of first vaccination, compared to a control.
42. The method of any one of claims 32-41, wherein the control is:(a) an accepted reference;(b) the amount of methane, CO2-normalized methane, hydrogen, or carbon dioxide emitted by an unvaccinated subject; or(c) the amount of methane, CO2-normalized methane, hydrogen, or carbon dioxide emitted by the vaccinated subject prior to vaccination.
43. The method of any one of claims 23-42, wherein the subject produces an antibody against at least one methanogen.
44. The method of claim 43, wherein the antibody is an IgG, IgM, or an IgA, preferably an IgA or IgM.
45. The method of claim 43 or 44, wherein the antibody is produced in an amount sufficient to:(a) be detectable in the digestive tract;(b) reduce the number and / or alter the relative abundances of methanogens in the digestive tract;(c) reduce the amount of methane, the CO2-normalized methane, and / or hydrogen emitted by the subject; and / or(d) increase the amount of CO2 emitted by the subject.
46. The method of any one of claims 23-45, wherein the vaccine composition is administered to the subject via a route selected from intramuscular administration, intradermal administration, subcutaneous administration, and nasal administration.
47. The method of any one of claims 23-46, wherein the vaccine composition is administered to the subject via intramuscular administration or subcutaneous administration, preferably subcutaneous administration.
48. The method of any one of claims 23-47, wherein the subject is administered with at least one repeat dose of the vaccine composition of any one of claims 1-22.
49. The method of claim 48, wherien the subject is administered with at least two repeat doses of the vaccine composition.
50. The method of claim 48 or 49, wherein the subject is administered with the vaccine composition at least 3 times per year.
51. The method of any one of claims 48-50, wherein the at least one repeat dose comprises the same dose or a different dose compared to the preceding dose of the vaccine composition.
52. The method of any one of claims 48-51, wherein the at least one repeat dose comprises the same adjuvant or a different adjuvant compared to the preceding dose of the vaccine composition.
53. The method of any one of claims 48-52, wherein the subject is administered with the repeat dose of the vaccine composition after at least about 2 weeks, about 3 weeks, about 1 month, about 6 months, or about 12 months from the time the subject is administered with the preceding dose of the vaccine composition.
54. The method of any one of claims 48-53, wherein the subject is administered with the repeat dose of the vaccine composition no later than about 1 month, about 2 months, about 3 months, 6 months, 12 months, 18 months, or 24 months from the time the subject is administered with the preceding dose of the vaccine composition.
55. The method of any one of claims 48-54, wherein the subject receives the repeat dose of the vaccine after at least about 2 weeks and no more than about 18 months from the time the subject is administered with the preceding dose of the vaccine.
56. The method of any one of claims 48-55, wherein the subject is administered with at least two repeat doses of the vaccine composition, and the subject receives:(a) the first repeat dose (“boost 1”) after about 2 weeks to about 4 weeks from the time the subject is administered with the initial vaccine dose (“prime”); and / or(b) the second repeat dose (“boost 2”) after about 3 months to about 6 months from the time the subject is administered with the initial vaccine dose (“prime”).
57. The method of any one of claims 23-56, wherein the subject is administered with a dosage of between about 0.1 mg of protein per kg of animal body weight and about 250 mg of protein per kg of animal body weight of the vaccine composition each time of vaccination.
58. The method of any one of claims 23-57, further comprising administering to the subject (a) at least one agent that reduces the level of methane and / or hydrogen produced by the subject; and / or (b) at least one agent that increases production efficiency.
59. The method of claim 58, wherein the at least one agent is administered to a subject concomitant with, prior to, or after the vaccination.
60. The method of claim 58 or 59, wherein the at least one agent is administered to a subject after the vaccination.
61. The method of any one of claims 58-60, wherein the at least one agent is administered to a subject daily, semiweekly, weekly, biweekly (every two weeks), or monthly.
62. The method of any one of claims 58-61, wherein the at least one agent is administered to a subject for a duration of at least 1 week but no more than 1 month.
63. The method of any one of claims 58-62, wherein the at least one agent comprises:(a) an agent selected from the agents listed in Tables 9-13;(b) 3-Nitrooxypropanol (3NOP), ethyl-3NOP, 2-bromoethanesulfonate (BES), 2-chloroethanesulfonate (CES), 3-bromopropanesulfonate (BPS), bromochloromethane (BCM), bromoform, bromodichloromethane, dibromochloromethane, carbon tetrachloride, trichloroacetamide, trichloroethyladipate, lumazin (2,4-pteridinedione), / ?-aminobenzoic acid, lovastatin, mevastatin, pravastatin, diallyl disulfide, garlic oil, saponins, tannins, flavonoids, nitrate, nitroethane, -nitro-propionate, 2-nitropropanol, 2-nitroethanol, malate, acrylate, oxaloacetate, fumarate, propynoic acid, 3-butenoic acid, 2-butynoic acid, ethyl 2-butynoate, monensin, lasalocid, bovicin HC5, nisin, or any combination thereof; and / or(c) Monensin (Rumensin®), Optigrid® 45 (ractopamine hydrochloride), Amprolium (Corid), Bacitracin (Albac, BMD), Bambermycin (GainPro), Decoquinate (Deccox), Fenbendazole (Safe-Guard), Laidlomycin (Cattlyst), Lasalocid (Bovetec), Melengestrol Acetate (MGA), Methoprene (Altosid), Morantel (Rumatel), Poloxalene (Bloat Guard), Ractopamine (Optaflexx, Actogain), Tetraclovinphos (Rabon), or any combination thereof.
64. The method of any one of claims 58-63, wherein the at least one agent is 3NOP or ethyl-3NOP.
65. The method of claim 64, wherein the subject is administered with(a) at least about 0.5 g but no more than 25 g of 3NOP per day;(b) at least about 1 g but no more than 5 g of 3NOP per day; or (c) about 2.5 g of 3NOP per day.
66. The method of claim 64 or 65, wherein the subject is administered with 3NOP for a duration of at least 1 week but no more than 1 month.
67. The method of any one of claims 55-66, wherein the at least one agent is formulated in animal feed.
68. The method of claim 58, wherein the at least one agent is a composition comprising one or more small molecules that reduce the production of one or more deleterious atmospheric gases and / or precursors thereof and one or more agriculturally suitable carriers.
69. The method of claim 68, wherein the one or more agriculturally suitable carriers comprises a solid carrier.
70. The method of claim 69, wherein the one or more solid carriers comprises attapulgite, kaolinite, fuller’s earth, calcium carbonate, perlite, diatomaceous earth, calcium silicate, fly ash, a polysaccharide, a disaccharide, a monosaccharide, a gum, a natural or synthetic derivative thereof, or a combination thereof.
71. The method of claim 69, wherein the one or more solid carriers comprises attapulgite, kaolinite, fuller’s earth, calcium carbonate, perlite, diatomaceous earth, calcium silicate, fly ash, a polysaccharide, a disaccharide, a monosaccharide, a gum, silica, propylene glycol, hemp protein, biochar, montmorillonite, activated charcoal, lignin, wood flour, hemp protein, pea protein, soy protein, gelatin, casein, chotsan, talc, calcium phosphate, arginine, lysine, calcium carbonate, carbon black, glutamine, betaine, bismuth phosphate, bismuth citrate, iron phosphate, or any combination thereof.
72. The method of any one of claims 69-71, wherein the one or more solid carriers comprises a saccharide comprising cellulose, xanthan gum, karaya gum, ethylcellulose, inositol, galactose, arabinose, lactose, lactulose, mannitol, mannose, sorbose, turanose, platinose, or a combination thereof.
73. The method of any one of claims 69-71, wherein the one or more solid carriers comprises a saccharide comprising cellulose, xanthan gum, karaya gum, ethylcellulose, inositol, galactose, arabinose, lactose, lactulose, mannitol, mannose, sorbose, turanose, platinose, carrageenan, cellulose acetate, hydroxypropyl cellulose, cellulose acteate phthalate, maltrodextran, dextran, inulin, com starch, amylopectin, sodium startch glycolate, pentaerthritol, cyclodextrin, or a combination thereof.
74. The method of any one of claims 69-73, wherein the solid carrier comprises silica and ethylcellulose.
75. The method of claim 74, wherein the carrier comprises about 10% to about 50% by weight of the silica and about 50 to about 90% by weight of the ethylcelluose.
76. The method of any one of claims 69-73, wherein the carrier comprises silica and activated charcoal.
77. The method of any one of claims 69-73, wherein the carrier comprises about 10% to about 90% by weight of the silica and about 10% to about 90% by weight of the activated charcoal.
78. The method of any one of claims 77, wherein the carrier further comprises arginine, lysine, or both arginine and lysine.
79. The method of any one of claims 69-73, wherein the carrier comprises activated charcoal and ethylcellulose.
80. The method of claim 79, wherein the carrier comprises about 10% to about 50% by weight of the activated charcoal and about 40% to about 90% by weight of the ethylcellulose.
81. The method of claim 79 or 80, wherien the carrier further comprises about 1 to about 10% by weight of sodium lignosulfate or about 1 to about 10% by weight of hydroxy ethyl cellulose.
82. The method of any one of claims 69-73, wherein the carrier comprises arginine and polycaprolactone.
83. The method of claim 82, wherein the carrier comprises about 10 to about 60% by weight of the arginine and about 30 to about 90% by weight of the poly caprolactone.
84. The method of any one of claims 69-73, wherein the carrier comprises silica and polycaprolactone.
85. The method of claim 84, wherein the carrier comprises about 10 to about 60% by weight of the silica and about 30 to about 90% by weight of the polycaprolactone.
86. The method of any one of claims 69-85, wherein the one or more solid carriers is inert.
87. The method of any one of claims 69-86, wherein the one or more solid carriers is watersoluble.
88. The method of any one of claims 69-87, further comprising one or more additives with adensity greater than water and / or one or more additives that reduces the rate of dissolution of the composition in water.
89. The method of claim 88, wherein the composition has a density of at least 1.1, preferably about 1.1 mg / mL to about 3 mg / mL, about 1.5 to about 3 mg / mL, about 1.5 to about 2.5 mg / mL, or about 1.5 to about 2 mg / mL.
90. The method of claim 88 or 89, wherein the one or more additives with a density greater than water comprises silica, attapulgite, kaolinite, fuller’s earth, calcium carbonate, perlite, diatomaceous earth, calcium silicate, fly ash, or any combination thereof.
91. The method of any one of claims 88-90, wherein the one or more additives that reduces the rate of dissolution of the composition further reduces a rate of release of the one or more small molecules into water.
92. The method of claim 91, wherein the composition dissolves over at least about 1, 2, 3, 4, 5, 6, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84, 91, 98, 105, 112, 119, 126, 133, 140, and / or nor more than about 2, 3, 4, 5, 6, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84, 91, 98, 105, 112, 119, 126, 133, 140, or 147 days, about 1 to about 147 days, more preferably 7-63 days, more preferably about 7-42 days, even more preferably 14-42 days yet even more preferably 14-28 days.
93. The method of any one of claims 69-92, wherein about 40 to about 80% of the small molecules that reduce the production of one or more deleterious atmospheric gases and / or precursors is thereof is released in water after 15 days.
94. The method of any one of claims 69-93, wherein the composition comprises particles having a uniform size distribution.
95. The method of any one of claims 69-94, wherein the composition comprises particles having a non-uniform size distribution.
96. The method of claim 94 or 95, wherein the particles comprise a spherical-, square-, rectangular-, capsular-, cylindrical-, conical-, ovular-, triangular-, diamond-, or disk-like shape.
97. The method of any one of claims 69-96, wherein the particles have a size ranging from about 1 mm to about 20 mm, about 1 to about 15 mm, about 1 to about 10 mm, about 5 to about 20 mm, about 5 to about 15 mm, or about 5 to about 10 mm.
98. The method of any one of claims 69-97, wherein the particles further comprises a coating.
99. The method of claim 98, wherein the coating comprises at least two layers.
100. The method of claim 98 or 99, wherein the coating is selected from cellulose acetatephlalate, ethyl cellulose, hydroxypropyl cellulose, polycaprolactone,alginate, chitosan,polyethylene glycol, cellulose actate, triacetin, propylene glycol, n-methyl-2-pyrollidone, and any combination thereof.
101. The method of claim 98 or 99, wherein the coating comprises two or more polyelectrolytes.
102. The method of claim 101, wherein the polyelelctrolytes comprise polystyrene sulfonate, polyethyleneimine, sodium lignosulfate, polyglutamic acid and poly-L-lysine, poly-L-arginine, polyallylamine hydrochloride, polyacrylic acid, or any combination thereof.
103. The method of claim 102, wherein the poly electrolytes comprise polyallylamine hydrochloride and sodium lignosulfate.
104. The method of claim 102, wherein the poly electrolytes comprise polyallylamine hydrochloride and polystyrene suylfonate.
105. The method of claim 102, wherein the poly electrolytes comprise sodium lignosulfate and one of polyglutamic acid and poly-L-lysine, or poly-L-arginine, and sodium lignosulfate.
106. The method of claim 102, wherein the poly electrolytes comprise polystyrene sulfonate and one of polyglutamic acid and poly-L-lysine, or poly-L-arginine.
107. The method of any one of claims 101-106, wherein the two or more polyelectrolytes are crosslinked.
108. The method of any one of claims 69-107, wherein the one or more small molecules comprise a molecule that interferes with the uptake and / or conversion of acetate, H2, CO2, methanol, monomethylamine, dimethylamine, trimethylamine, nitric oxide, or a combination thereof.
109. The method of any one of claims 69-108, wherein the one or more small molecules that reduce the production of one or more deleterious atmospheric gases and / or precursors interact with an enzyme selected from the group consisting of 3-(methylthio)propanoate:coenzyme M methyltransferase, acetate kinase, acetyl-CoA decarbonylase, acetyl-CoAdecarbonylase / synthase complex 01282, acetyl-CoA decarbonylase / synthase complex p, acetyl-CoA decarbonylase / synthase complex y5, acetyl-CoA synthase, carbon monoxide dehydrogenase, carbonic anhydrase, Co-methyltransferase, coenzyme M reductase, cyclohydrolase, dehydrogenase, dimethylamine—[corrinoid protein] Co-methyltransferase, F420-dependent methylene-H4MPT reductase, F42o-dependent methylene-H4SPT dehydrogenase, formylmethanofuran dehydrogenase, formylmethanofuran:H4MPT formyltransferase, formylmethanofuran:H4SPT formyltransferase, formyltransferase, H2-forming methylene-H4MPT dehydrogenase, methanol-5-hydroxybenzimidazolylcobamide Co-methyltransferase, methenyl-H4MPT cyclohydrolase, methyl-coenzyme M reductase, methyl-H4SPT:CoM methyltransferase, methylated [methylamine-specific corrinoid protein]:coenzyme M methyltransferase, methylcobamide:CoM methyltransferase, methylthiol:coenzyme M methyltransferase, methyl transferase, MtaC protein: coenzyme M methyltransferase, phosphotransacetylase, tetrahydromethanopterin S-methyltransferase, tetramethylammonium methyltransferase, trimethylamine—corrinoid protein Co-methyltransferase, and any combination thereof.
110. The method of claim 109, wherein the one or more small molecules that reduce the production of one or more deleterious atmospheric gases and / or precursors interact with methylcoenzyme M reductase (MCR).
111. The method of any one of claims 69-110, wherein the one or more small molecules that reduce the production of one or more deleterious atmospheric gases and / or precursors comprise a compound having the formula R1-[CH2]n-ONO2 whereinn is an integer from 1 to 15;R1 is selected from the group consisting of H, Ci-Cealkyl, phenyl, —OH, —NH2, —CN,—COOH, — O(C=O)R3, —NHC(=O)R3, SO2NHR3, or —ONO2, —SH and R3 is Ci-Cealkyl, phenyl, pyridyl;with the proviso that when n is >3 the hydrocarbon chain may be interrupted by —O— or — NH—.
112. The method of claim 111, wherein the one or more small molecules that reduce the production of one or more deleterious atmospheric gases and / or precursors is selected from 3-nitrooxypropanol, 9-nitrooxynonanol, 5-nitrooxy pentanoic acid, 6-nitrooxy hexanoic acid,bis(2-hydroxyethyl)amine dinitrate, 1,4-bis-nitrooxybutane, 1,5-bis-nitrooxypentane, and any combination thereof.
113. The method of claim 111, wherein the one or more small molecules that reduce the production of one or more deleterious atmospheric gases and / or precursors comprises 3-nitrooxypropanol (3NOP).
114. The method of any one of claims 69-113, wherein the composition comprises about 1 to about 25% by weight of the small molecule, about 5 to about 20% by weight of the small molecule, or about 5 to about 15% by weight of the small molecule.
115. The method of any one of claims 69-114, wherein the composition comprises a plurality of populations of particles, wherein each population or particles comprises a different formulation, a different shape, and / or a different size distribution.
116. The method of claim 115, wherein the plurality of populations of particles comprises a first population and a second population.
117. The method of claim 116, wherein the population of granular particles further comprises at least 1, 2, 3, 4, 5, 5, 6, 8, or 9 and / or no more than 4, 5, 6, 7, 8, 9, or 10 additional populations, for example 3-10 additional populations, preferably 3-7 additional populations, more preferably 3-5 additional populations.
118. The method of claim 115 or 116, wherein the first population comprises an immediate release formulation.
119. The method of any one of claims 116-118, wherein the second population comprises a delayed release formulation.
120. The method of any one of claims 117-119, wherein each additional population comprises a delayed release formulation, wherein each population dissolves and / or releases the one or more small molecules that reduce the production of one or more deleterious atmospheric gases and / or precursors at a different time than each of the other populations.
121. An antibody produced by the method of any one of claims 23-120, or an antigen-binding fragment thereof.
122. The antibody of claim 121, wherein the antibody is a monoclonal antibody.
123. The antibody of claim 121 or 122, wherein the antibody is an IgM, an IgG or an IgA, preferably an IgA or an IgM.
124. The antibody of any one of claims 121-123, wherein the antibody is lyophilized.
125. The antibody of any one of claims 121-124, wherein the antibody is in a pharmaceuticalcomposition, optionally comprising at least one excipient and / or carrier.
126. Milk and / or a derivative thereof produced by the subject of any one of claims 23-120.
127. The milk and / or a derivative thereof of claim 126, wherein the milk and / or derivatives thereof comprises an antibody that binds at least one methanogen.
128. The milk and / or a derivative thereof of claim 126 or 127, wherein the milk and / or derivatives thereof is pasteurized and / or homogenized.
129. The milk and / or a derivative thereof of any one of claims 127-128, wherein the milk and / or derivatives thereof is lyophilized or evaporated to form dry milk powder (e.g., boiling at low pressure at low temperature).
130. The milk and / or a derivative thereof of any one of claims 126-129, further comprising at least one agent that reduces methane and / or hydrogen production in a subject, optionally wherein the at least one agent is selected from the agents in Table 9.
131. An animal feed comprising:(a) the antibody of any one of claims 121-125;(b) at least one agent that reduces methane and / or hydrogen production in a subject, optionally wherein the at least one agent is selected from the agents in Tables 9-13;(c) the milk of any one of claims 126-130; or(d) any combination of two or more of (a)-(c).
132. The animal feed of claim 131, wherein the animal feed is liquid (e.g., drinking water, milk) or solid (e.g., fodder).
133. The animal feed of claim 131 or 132, wherein the animal feed comprises fat and / or fatty acid, optionally wherein the animal feed comprises fat and / or fatty acid that is at least about 1%, 2%, 3%, 4%, 5%, or 6% of the diet.
134. A method of reducing methane and / or hydrogen production or increasing CO2 production in a subject, the method comprising orally administering to and / or feeding the subject the antibody of any one of claims 121-125, the milk and / or a derivative thereof of any one of claims 126-130, the animal feed of any one of claims 131-133, or any combination of two or more thereof.
135. The method of claim 134, further comprising administering at least one agent that reduces methane and / or hydrogen production in a subject, optionally wherein the at least one agent is selected from the agents in Tables 9-13.
136. The method of claim 134 or 135, further comprising administering the subject with the at least one vaccine composition of any one of claims 1-22.
137. The method of any one of claims 23-120 and 134-136, wherein the subject is a mammal, a human, a canine, a feline, or a ruminant.
138. The method of claim 137, whereinthe ruminant is selected from a cow, cattle, a bull, a bison, a yak, a buffalo, an antelope, a goat, a sheep, a deer, a giraffe, a caribou, a gazelle, a macropod, a llama, a camel, and an alpaca.
139. The method of any one of claims 23-120 and 134-138, wherein the subject is cattle.
140. The method of claim 139, wherein the cattle is selected from a pregnant cow, heifer, bull,and steer.
141. The method of any one of claims 23-120 and 134-140, wherein the subject is an adult.
142. The method of claim 141, wherein the subject is adult cattle selected from:(a) a cow that is about 6-8 months to about 2-7 years old;(a) a beef adult that is about 1.5 years to about 2.5 years old; and(b) a dairy adult that is about 4 years to 7 years old.
143. The method of any one of claims 23-120 and 134-140, wherein the subject is a young subject (e.g., before weaning or below 2 years of age).
144. The method of claim 143, wherein the subject is young cattle selected from:(a) a newborn calf and a pre-weaned calf that is about 0 month to about 3 months old; and(b) a weaned cow that is about 3 months to 8 months old.
145. The method of any one of claims 23-120 and 134-140, wherein the subject is a pregnant female subject.
146. The method of any one of claims 23-120 and 134-140, wherein the subject is an offspring (e.g., calf) of the vaccinated female subject that received the milk comprising an antibody that binds at least one methanogen.
147. The method of any one of claims 23-120 and 134-146, wherein the vaccine is administered to a subject as a part of a pre-existing vaccination program to which the subject is subject (e.g., Table 14).
148. The method of any one of claims 23-120 and 134-147, wherein the vaccine is administered to a subject when the subject is subject to or receives at least one other vaccine, wherein the at least one other vaccine is against against infectious bovine rhinotracheitis (IBR), bovine virus diarrhea (BVD), parainfluenza-3 (PI3), bovine respiratory syncytial virus (BRSV), Clostridia, E. Coli mastitis, leptospirosis, mannheimia hemolytica, brucella, vibriosis, Campylobacter, trichomonas, trichomoniasis, rotavirus, coronavirus, and / or respiratory disease.
149. The method of any one of claims 23-120 and 134-148, wherein the vaccine is administered to a subject when the subject changes in hands and / or a changes in environment.
150. The method of any one of claims 23-120 and 134-149, wherien the vaccine reduces methane and / or hydrogen production in the lower intestinal track (lower bowel) or the rumen of the subject.
151. The method of claim 150, wherein the method results in at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% reduction in the level of methane and / or hydrogen produced by the subject, optionally wherein the reduction in the level of methane and / or hydrogen is compared to an untreated subject.
152. A kit comprising the vaccine composition of any one of claims 1-22.
153. The kit of claim 152, wherein the vaccine composition comprises no more than one polypeptide or peptide.
154. The kit of claim 152, wherein the vaccine composition comprises:(a) at least two polypeptides;(b) at least two peptides; or(c) at least one polypeptide and at least one peptide.
155. The kit of claim 152, wherein the kit comprises at least two vaccine compositions, each comprising different polypeptide(s) and / or peptide(s).
156. The kit of claim 155, wherein the at least two vaccine compositions are in separate containers.
157. The kit of any one of claims 152-156, wherein the kit comprises about or at least about 1, 2, 3, 4, 5, 10, 20, 50, 100, 250, 500, 1000, 1500, 2000, 2500, or 3000 doses of the vaccine composition.
158. The kit of claim 157, wherein(a) all doses are in a single container;(b) each dose is in an individual container; or(c) about or at least about 2, 3, 4, 5, 10, 25, 50, or 100 doses are pooled in a single container.
159. The kit of any one of claims 152-158, further comprising at least one adjuvant.
160. The kit of claim 159, wherein the vaccine composition and the at least one adjuvant arein separate containers.
161. The kit of claim 159 or 160, wherein the kit comprises at least about 1, 2, 3, 4, 5, 10, 20, 50, 100, 250, 500, 1000, 1500, 2000, 2500, or 3000 doses; and(a) all doses are in a single container, and the at least one adjuvant for all doses are in a separate single container;(b) each dose is in an individual container, and the at least one adjuvant for all doses are in a separate single container;(c) each dose is in an individual container, and the at least one adjuvant for each dose is in a separate individual container; or(d) about or at least about 2, 3, 4, 5, 10, 25, 50, or 100 doses are pooled in a single container, and the pooled amount of at least one adjuvant for the pooled doses are in a separate single container.
162. The kit of any one of claims 159-161, wherein the kit comprises at least two adjuvants that are different.
163. A method of treating a subject afflicted with a disease, the method comprising to the subject:(a) the vaccine composition of any one of claims 1-22;(b) the antibody of any one of claims 121-125;(c) the milk and / or derivative thereof of any one of claims 126-130;(d) the animal feed of any one of claims 131-133;(e) at least one agent that reduces methane and / or hydrogen production in a subject, optionally wherein the at least one agent is selected from the agents in Tables 9-13; or(f) any combination of two or more thereof.
164. The method of claim 163, wherein the subject is selected from a mammal, ruminant, a canine, a feline, and a human, optionally wherein the ruminant is selected from a cow, cattle, a bull, a bison, a yak, a buffalo, an antelope, a goat, a sheep, a deer, a giraffe, a caribou, a gazelle, a macropod, a llama, a camel, and an alpaca.
165. A method of reducing CH4 emissions in a ruminant comprising administering to the ruminant a vaccine composition comprising at least one polypeptide and / or at least one peptide of at least one cell surface protein or a fragment thereof (e.g., an antigenic fragment, e.g., a fragment comprising an epitope, e.g., a fragment comprising an extracellular domain or a portion thereof) of at least one methanogen, wherein the CH4 emissions are reduced by at least about 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% as compared to an untreated control ruminant.
166. A method of reducing H2 emissions in a ruminant comprising administering to the ruminant a vaccine composition comprising at least one polypeptide and / or at least one peptide of at least one cell surface protein or a fragment thereof (e.g., an antigenic fragment, e.g., a fragment comprising an epitope, e.g., a fragment comprising an extracellular domain or a portion thereof) of at least one methanogen, wherein the H2 emissions are reduced by at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, or 50% as compared to an untreated control ruminant.
167. A method of increasing the productivity of a ruminant comprising administering to the ruminant a vaccine composition comprising at least one polypeptide and / or at least one peptide of at least one cell surface protein or a fragment thereof (e.g., an antigenic fragment, e.g., a fragment comprising an epitope, e.g., a fragment comprising an extracellular domain or a portion thereof) of at least one methanogen, wherein the productivity is increased by at least about 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%, 10.5%, 11%, 11.5%, 12%, 12.5%, 13%, 13.5%, 14%, 14.5%, or 15% as compared to an untreated control ruminant.
168. The method of any one of claims 165-167, wherein the vaccine composition comprises the vaccine composition of any one of claims 1-22.
169. The method of any one of claims 165-168, wherein the ruminant is cattle.
170. An animal injected subcutaneously with the vaccine composition of any one of claims 122, wherein the vaccine composition comprises about a dosage of between 0.1 mg / kg and 250 mg / kg, or any range in between or any value in between.
171. A method of producing a low carbon animal product, the method comprising:(a) administering to an animal (e.g., a mammal, a ruminant) a vaccine composition of any one of claims 1-22;(b) determining an amount of emissions of at least one greenhouse gas (e.g., CO2, CH4, N2O, and / or H2) from the animal of (a) following administration until animal product harvesting;(c) determining a first carbon intensity as a ratio of a first amount of emissions from the vaccinated animal in (b) and the amount of harvested animal product;(d) determining a second carbon intensity as a ratio of a second amount of carbon emissions from an untreated animal and the same amount of harvested animal product; and(e) determining the difference between the first carbon intensity and the second carbon intensity.
172. The method of claim 171, wherein determining the amount of emissions comprises measuring the emissions using a GreenFeed system.
173. The method of claim 171, wherein the animal product is selected from the group consisting of meat, milk, and wool.
174. The method of claim 171, further comprising administering to the animal at least one agent that reduces methane and / or hydrogen production.
175. The method of claim 171, further comprising certifying the animal product as a low carbon intensity product based on the determined difference between the first carbon intensity and the second carbon intensity.