DNA antibody constructs targeting pneumococcal histidine triad protein

Abstract

Disclosed herein is an antibody to pneumococcal histidine triad protein D (PhtD) as well as nucleic acid molecules encoding the anti-PhtD antibody and compositions comprising the antibody or nucleic acid molecules encoding the antibody. The disclosure also provides a method of preventing and / or treating a bacterial infection in a subject using the antibody or nucleic acid molecules.

Description

[0001]Docket No.206193-0136-00WO DNA ANTIBODY CONSTRUCTS TARGETING PNEUMOCOCCAL HISTIDINE TRIAD PROTEIN CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 637,201, filed April 22, 2024, and U.S. Provisional Application No.63 / 644,015, filed May 08, 2024, each of which is hereby incorporated by reference herein in its entirety. TECHNICAL FIELD The present invention relates to a composition comprising a recombinant nucleic acid sequence for generating one or more synthetic anitbodies, including an Fc- modified DNA-encoded monoclonal antibody targeting pneumococcal histidine triad protein D (PhtD), and functional fragments thereof, and a method of preventing and / or pneumococcal infection by administering said composition. BACKGROUND Streptococcus pneumoniae (pneumococcus, Spn) infection remains a leading cause of death globally despite widespread use of current capsular polysaccharide vaccines. Despite a reduction of pneumococcal disease, these vaccines are limited by serotype specificity with disease persisting for some vaccine serotypes due to immune system evasion capability (i.e., capsule shedding, electronegative cell surface). Therefore, there is a growing need for serotype-inclusive approaches to combat Spn infection. Thus there is need in the art for improved therapeutics that prevent and / or treat Streptococcus pneumoniae infection. The current invention satisfies this need. SUMMARY In some aspects, the present invention relates to an anti-PhtD (pneumococcal histidine triad protein D) antibody or fragment thereof. In some embodiments, the antibody, or fragment thereof, comprises a light chain selected from the group consisting of SEQ ID NO:5, and SEQ ID NO:7, or a fragment or variant thereof. Docket No.206193-0136-00WO In some embodiments, the antibody, or fragment thereof, comprises a heavy chain selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3, and SEQ ID NO: 9, or a fragment or variant thereof. In some embodiments, the antibody is selected from the group consisting of a humanized antibody, a chimeric antibody, a fully human antibody, an antibody mimetic. In some embodiments, the invention relates to a nucleic acid molecule encoding a light chain of an anti-PhtD antibody, or fragment thereof. In some embodiments, the nucleotide sequence encoding the light chain is selected from the group consisting of: SEQ ID NO:6, SEQ ID and NO:8, or a fragment thereof. In some embodiments, the invention relates to a nucleic acid molecule encoding a heavy chain of an anti-PhtD antibody, or fragment thereof. In some embodiments, the nucleotide sequence encoding the heavy chain is selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:4, and SEQ ID NO:10, or a fragment thereof. In some embodiments, the nucleotide sequence encodes a leader sequence. In some embodiments, the nucleic acid molecule comprises an expression vector. In some embodiments, the present invention relates to a combination of nucleic acid molecules encoding an anti-PhtD antibody, comprising a first nucleic acid molecule encoding the light chain amino acid sequence, and a second nucleic acid molecule encoding the heavy chain amino acid sequence, or a fragment thereof. In some embodiments, the nucleotide sequence encoding the light chain is selected from the group consisting of: SEQ ID NO:6, and SEQ ID NO:8, or a fragment thereof, and wherein the nucleotide sequence encoding the heavy chain is selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:4, and SEQ ID NO:10, or a fragment thereof. In some embodiments, one or more nucleotide sequence encodes a leader sequence. In some embodiments, one or more nucleic acid molecule comprises an expression vector. In some embodiments, the invention relates to a composition comprising at least one anti-PhtD antibody or fragment thereof. In some embodiments, the invention relates to a composition comprising at least one nucleic acid molecule encoding an anti-PhtD antibody or a fragment thereof. Docket No.206193-0136-00WO In some embodiments, the invention relates to a composition comprising a combination of nucleic acid molecules encoding an anti-PhtD antibody. In some embodiments, the composition further comprises a pharmaceutically acceptable excipient. In some embodiments, the present invention relates to method of preventing or treating a disease in a subject, the method comprising administering to the subject the anti- PhtD antibody or antibody fragment described herein, the nucleic acid molecule encoding the anti-PhtD antibody or antibody fragment described herein, the combination of nucleic acid molecules encoding the anti-PhtD antibody or antibody fragment described herein, or or a composition described herein. In some embodiments, the disease is Streptococcus pneumoniae infection. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1A – 1C: A) Design and optimization of monoclonal antibody PhtD3. Germline reversions added to the non-essential framework regions to improve in vivo expression. B)Serum concentration of in vivo expressed WT PhtD3 and Germline reverted PhtD3 (GR) DMAbs post-single injection (n=5, BALB / c, 100 µg dose). C) Serum expressed WT PhtD3 and GR PhtD3 DMAbs Day 530-post single administration. Figure 2A – 2E: A) PhtD3 (GR) DMAb dose titration intranasal WU2 challenge timeline in male C57BL / 6 mice (4-6 weeks old; n=12 per group). Control rPhtD3 mAb mice were administered at the time of challenge start. B) Expression of PhtD3 (GR) DMAb by dose prior to shipment. C) in vivo expression of PhtD3 (GR) DMAb by dose over time post-single administration (n=3). D) Percent weight change for all groups during the duration of WU2 challenge. E) Prophylactic efficacy of PhtD3 DMAb doses compared to recombinant PhtD3 mAb (300 µg per mouse) (no significance between Ab groups via log- rank (Mantel-Cox) test) (n=4-7 mice / group). Figure 3A – 3C: A) Design of complement enhanced PhtD3 DMAb variant using the increased durability germline reverted (GR) dual plasmid system by the addition of an E430G point mutation in the heavy chain (HC). B) Serum concentration of in vivo expressed WT PhtD3 (GR) and E430G PhtD3 DMAbs at high (200 ug) and low (25 ug) doses (n=5; BALB / c). C) in vitro produced PhtD3 DMAbs binding to full length protein, epitope region AA 1-343, and WU2 pneumococcus compared to recombinant PhtD3 mAb and Isotype IgG control (all samples start at 5 mg / mL diluted 4-fold). Docket No.206193-0136-00WO Figure 4A – 4F: A) PhtD3 DMAb variant dose outline for WU2 intranasal challenge. B) Expression levels of PhtD3 DMAb variants at high and low doses 28-days post injection in BAL fluid. C) Percent weight change for all groups during the duration of WU2 challenge. D) Prophylactic efficacy of PhtD3 DMAb doses compared to recombinant PhtD3 mAb (300 ug per mouse) (statistical significance between groups determined via Mantel-Cox test; n=12 mice / group). E) Lung WU2 titers 3-days post infection of all treatment groups in comparison to naïve mice (statistical significance determined via one-way ANOVA, p-value <0.05). F) Blood WU2 titers 3-days post infection of all treatment groups in comparison to naïve mice (one-way ANOVA, pvalue <0.05). DETAILED DESCRIPTION The invention relates to compositions comprising a recombinant nucleic acid sequence encoding an antibody, a fragment thereof, a variant thereof, or a combination thereof. In some embodiments, the antibody is an anti-PhtD antibody. The composition can be administered to a subject in need thereof to facilitate in vivo expression and formation of a synthetic antibody. In particular, the heavy chain and light chain polypeptides expressed from the recombinant nucleic acid sequences can assemble into the synthetic antibody. The heavy chain polypeptide and the light chain polypeptide can interact with one another such that assembly results in the synthetic antibody being capable of binding the antigen, being more immunogenic as compared to an antibody not assembled as described herein, and being capable of eliciting or inducing an immune response against the antigen. Additionally, these synthetic antibodies are generated more rapidly in the subject than antibodies that are produced in response to antigen induced immune response. The synthetic antibodies are able to effectively bind and neutralize a range of antigens. The synthetic antibodies are also able to effectively protect against and / or promote survival of disease. Definitions Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In case of conflict, the present document, including definitions, will control. Preferred methods and materials are described below, although methods and materials similar or equivalent to those Docket No.206193-0136-00WO described herein can be used in practice or testing of the present invention. All publications, patent applications, patents and other references mentioned herein are incorporated by reference in their entirety. The materials, methods, and examples disclosed herein are illustrative only and not intended to be limiting. The terms “comprise(s),” “include(s),” “having,” “has,” “can,” “contain(s),” and variants thereof, as used herein, are intended to be open-ended transitional phrases, terms, or words that do not preclude the possibility of additional acts or structures. The singular forms “a,” “and” and “the” include plural references unless the context clearly dictates otherwise. The present disclosure also contemplates other embodiments “comprising,” “consisting of” and “consisting essentially of,” the embodiments or elements presented herein, whether explicitly set forth or not. “Antibody” may mean an antibody of classes IgG, IgM, IgA, IgD or IgE, or fragments, fragments or derivatives thereof, including Fab, F(ab')2, Fd, and single chain antibodies, and derivatives thereof. The antibody may be an antibody isolated from the serum sample of mammal, a polyclonal antibody, affinity purified antibody, or mixtures thereof which exhibits sufficient binding specificity to a desired epitope or a sequence derived therefrom. “Antibody fragment” or “fragment of an antibody” as used interchangeably herein refers to a portion of an intact antibody comprising the antigen-binding site or variable region. Examples of antibody fragments include, but are not limited to, Fab fragments, Fab' fragments, Fab'-SH fragments, F(ab')2 fragments, Fd fragments, Fv fragments, diabodies, single-chain Fv (scFv) molecules, single-chain polypeptides containing only one light chain variable domain, single-chain polypeptides containing the three CDRs of the light-chain variable domain, single-chain polypeptides containing only one heavy chain variable region, and single-chain polypeptides containing the three CDRs of the heavy chain variable region. “Antigen” refers to proteins that have the ability to generate an immune response in a host. An antigen may be recognized and bound by an antibody. An antigen may originate from within the body or from the external environment. “Coding sequence” or “encoding nucleic acid” as used herein may mean refers to the nucleic acid (RNA or DNA molecule) that comprise a nucleotide sequence which encodes an antibody as set forth herein. The coding sequence may further include initiation and termination signals operably linked to regulatory elements including a promoter and polyadenylation signal capable of directing expression in the cells of an individual or Docket No.206193-0136-00WO mammal to whom the nucleic acid is administered. The coding sequence may further include sequences that encode signal peptides. “Complement” or “complementary” as used herein may mean a nucleic acid may mean Watson-Crick (e.g., A-T / U and C-G) or Hoogsteen base pairing between nucleotides or nucleotide analogs of nucleic acid molecules. “Fragment” may mean a polypeptide fragment of an antibody that is function, i.e., can bind to desired target and have the same intended effect as a full length antibody. A fragment of an antibody may be 100% identical to the full length except missing at least one amino acid from the N and / or C terminal, in each case with or without signal peptides and / or a methionine at position 1. Fragments may comprise 20% or more, 25% or more, 30% or more, 35% or more, 40% or more, 45% or more, 50% or more, 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more percent of the length of the particular full length antibody, excluding any heterologous signal peptide added. The fragment may comprise a fragment of a polypeptide that is 95% or more, 96% or more, 97% or more, 98% or more or 99% or more identical to the antibody and additionally comprise an N terminal methionine or heterologous signal peptide which is not included when calculating percent identity. Fragments may further comprise an N terminal methionine and / or a signal peptide such as an immunoglobulin signal peptide, for example an IgE or IgG signal peptide. The N terminal methionine and / or signal peptide may be linked to a fragment of an antibody. A fragment of a nucleic acid sequence that encodes an antibody may be 100% identical to the full length except missing at least one nucleotide from the 5' and / or 3' end, in each case with or without sequences encoding signal peptides and / or a methionine at position 1. Fragments may comprise 20% or more, 25% or more, 30% or more, 35% or more, 40% or more, 45% or more, 50% or more, 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more percent of the length of the particular full length coding sequence, excluding any heterologous signal peptide added. The fragment may comprise a fragment that encode a polypeptide that is 95% or more, 96% or more, 97% or more, 98% or more or 99% or more identical to the antibody and additionally optionally comprise sequence encoding an N terminal methionine or heterologous signal peptide which is not included when calculating Docket No.206193-0136-00WO percent identity. Fragments may further comprise coding sequences for an N terminal methionine and / or a signal peptide such as an immunoglobulin signal peptide, for example an IgE or IgG signal peptide. The coding sequence encoding the N terminal methionine and / or signal peptide may be linked to a fragment of coding sequence. “Genetic construct” as used herein refers to the DNA or RNA molecules that comprise a nucleotide sequence which encodes a protein, such as an antibody. The coding sequence includes initiation and termination signals operably linked to regulatory elements including a promoter and polyadenylation signal capable of directing expression in the cells of the individual to whom the nucleic acid molecule is administered. As used herein, the term "expressible form" refers to gene constructs that contain the necessary regulatory elements operable linked to a coding sequence that encodes a protein such that when present in the cell of the individual, the coding sequence will be expressed. “Identical” or “identity” as used herein in the context of two or more nucleic acids or polypeptide sequences, may mean that the sequences have a specified percentage of residues that are the same over a specified region. The percentage may be calculated by optimally aligning the two sequences, comparing the two sequences over the specified region, determining the number of positions at which the identical residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the specified region, and multiplying the result by 100 to yield the percentage of sequence identity. In cases where the two sequences are of different lengths or the alignment produces one or more staggered ends and the specified region of comparison includes only a single sequence, the residues of single sequence are included in the denominator but not the numerator of the calculation. When comparing DNA and RNA, thymine (T) and uracil (U) may be considered equivalent. Identity may be performed manually or by using a computer sequence algorithm such as BLAST or BLAST 2.0. “Nucleic acid” or “oligonucleotide” or “polynucleotide” as used herein may mean at least two nucleotides covalently linked together. The depiction of a single strand also defines the sequence of the complementary strand. Thus, a nucleic acid also encompasses the complementary strand of a depicted single strand. Many variants of a nucleic acid may be used for the same purpose as a given nucleic acid. Thus, a nucleic acid also encompasses substantially identical nucleic acids and complements thereof. A single strand provides a probe that may hybridize to a target sequence under stringent hybridization conditions. Thus, Docket No.206193-0136-00WO a nucleic acid also encompasses a probe that hybridizes under stringent hybridization conditions. Nucleic acids may be single stranded or double stranded, or may contain portions of both double stranded and single stranded sequence. The nucleic acid may be DNA, both genomic and cDNA, RNA, or a hybrid, where the nucleic acid may contain combinations of deoxyribo- and ribo-nucleotides, and combinations of bases including uracil, adenine, thymine, cytosine, guanine, inosine, xanthine hypoxanthine, isocytosine and isoguanine. Nucleic acids may be obtained by chemical synthesis methods or by recombinant methods. “Operably linked” as used herein may mean that expression of a gene is under the control of a promoter with which it is spatially connected. A promoter may be positioned 5' (upstream) or 3' (downstream) of a gene under its control. The distance between the promoter and a gene may be approximately the same as the distance between that promoter and the gene it controls in the gene from which the promoter is derived. As is known in the art, variation in this distance may be accommodated without loss of promoter function. A “peptide,” “protein,” or “polypeptide” as used herein can mean a linked sequence of amino acids and can be natural, synthetic, or a modification or combination of natural and synthetic. “Promoter” as used herein may mean a synthetic or naturally-derived molecule which is capable of conferring, activating or enhancing expression of a nucleic acid in a cell. A promoter may comprise one or more specific transcriptional regulatory sequences to further enhance expression and / or to alter the spatial expression and / or temporal expression of same. A promoter may also comprise distal enhancer or repressor elements, which can be located as much as several thousand base pairs from the start site of transcription. A promoter may be derived from sources including viral, bacterial, fungal, plants, insects, and animals. A promoter may regulate the expression of a gene component constitutively, or differentially with respect to cell, the tissue or organ in which expression occurs or, with respect to the developmental stage at which expression occurs, or in response to external stimuli such as physiological stresses, pathogens, metal ions, or inducing agents. Representative examples of promoters include the bacteriophage T7 promoter, bacteriophage T3 promoter, SP6 promoter, lac operator-promoter, tac promoter, SV40 late promoter, SV40 early promoter, RSV-LTR promoter, CMV IE promoter, SV40 early promoter or SV 40 late promoter and the CMV IE promoter. Docket No.206193-0136-00WO “Signal peptide” and “leader sequence” are used interchangeably herein and refer to an amino acid sequence that can be linked at the amino terminus of a protein set forth herein. Signal peptides / leader sequences typically direct localization of a protein. Signal peptides / leader sequences used herein preferably facilitate secretion of the protein from the cell in which it is produced. Signal peptides / leader sequences are often cleaved from the remainder of the protein, often referred to as the mature protein, upon secretion from the cell. Signal peptides / leader sequences are linked at the N terminus of the protein. “Stringent hybridization conditions” as used herein may mean conditions under which a first nucleic acid sequence (e.g., probe) will hybridize to a second nucleic acid sequence (e.g., target), such as in a complex mixture of nucleic acids. Stringent conditions are sequence dependent and will be different in different circumstances. Stringent conditions may be selected to be about 5-10°C lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength pH. The Tm may be the temperature (under defined ionic strength, pH, and nucleic concentration) at which 50% of the probes complementary to the target hybridize to the target sequence at equilibrium (as the target sequences are present in excess, at Tm, 50% of the probes are occupied at equilibrium). Stringent conditions may be those in which the salt concentration is less than about 1.0 M sodium ion, such as about 0.01- 1.0 M sodium ion concentration (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30°C for short probes (e.g., about 10-50 nucleotides) and at least about 60°C for long probes (e.g., greater than about 50 nucleotides). Stringent conditions may also be achieved with the addition of destabilizing agents such as formamide. For selective or specific hybridization, a positive signal may be at least 2 to 10 times background hybridization. Exemplary stringent hybridization conditions include the following: 50% formamide, 5x SSC, and 1% SDS, incubating at 42°C, or, 5x SSC, 1% SDS, incubating at 65°C, with wash in 0.2x SSC, and 0.1% SDS at 65°C. “Subject” and “patient” as used herein interchangeably refers to any vertebrate, including, but not limited to, a mammal (e.g., cow, pig, camel, llama, horse, goat, rabbit, sheep, hamsters, guinea pig, cat, dog, rat, and mouse, a non-human primate (for example, a monkey, such as a cynomolgous or rhesus monkey, chimpanzee, etc) and a human). In some embodiments, the subject may be a human or a non-human. The subject or patient may be undergoing other forms of treatment. “Substantially complementary” as used herein may mean that a first sequence is at least 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, Docket No.206193-0136-00WO 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the complement of a second sequence over a region of 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 or more nucleotides or amino acids, or that the two sequences hybridize under stringent hybridization conditions. “Substantially identical” as used herein may mean that a first and second sequence are at least 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,or 99% over a region of 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, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100 or more nucleotides or amino acids, or with respect to nucleic acids, if the first sequence is substantially complementary to the complement of the second sequence. “Synthetic antibody” as used herein refers to an antibody that is encoded by the recombinant nucleic acid sequence described herein and is generated in a subject. “Treatment” or “treating,” as used herein can mean protecting of a subject from a disease through means of preventing, suppressing, repressing, or completely eliminating the disease. Preventing the disease involves administering a vaccine of the present invention to a subject prior to onset of the disease. Suppressing the disease involves administering a vaccine of the present invention to a subject after induction of the disease but before its clinical appearance. Repressing the disease involves administering a vaccine of the present invention to a subject after clinical appearance of the disease. “Variant” used herein with respect to a nucleic acid may mean (i) a portion or fragment of a referenced nucleotide sequence; (ii) the complement of a referenced nucleotide sequence or portion thereof; (iii) a nucleic acid that is substantially identical to a referenced nucleic acid or the complement thereof; or (iv) a nucleic acid that hybridizes under stringent conditions to the referenced nucleic acid, complement thereof, or a sequences substantially identical thereto. “Variant” with respect to a peptide or polypeptide that differs in amino acid sequence by the insertion, deletion, or conservative substitution of amino acids, but retain at least one biological activity. Variant may also mean a protein with an amino acid sequence that is substantially identical to a referenced protein with an amino acid sequence that retains at least one biological activity. A conservative substitution of an amino acid, i.e., replacing an amino acid with a different amino acid of similar properties (e.g., hydrophilicity, degree and distribution of charged regions) is recognized in the art as typically involving a minor change. Docket No.206193-0136-00WO These minor changes can be identified, in part, by considering the hydropathic index of amino acids, as understood in the art. Kyte et al., J. Mol. Biol.157:105-132 (1982). The hydropathic index of an amino acid is based on a consideration of its hydrophobicity and charge. It is known in the art that amino acids of similar hydropathic indexes can be substituted and still retain protein function. In one aspect, amino acids having hydropathic indexes of ±2 are substituted. The hydrophilicity of amino acids can also be used to reveal substitutions that would result in proteins retaining biological function. A consideration of the hydrophilicity of amino acids in the context of a peptide permits calculation of the greatest local average hydrophilicity of that peptide, a useful measure that has been reported to correlate well with antigenicity and immunogenicity. U.S. Patent No.4,554,101, incorporated fully herein by reference. Substitution of amino acids having similar hydrophilicity values can result in peptides retaining biological activity, for example immunogenicity, as is understood in the art. Substitutions may be performed with amino acids having hydrophilicity values within ±2 of each other. Both the hyrophobicity index and the hydrophilicity value of amino acids are influenced by the particular side chain of that amino acid. Consistent with that observation, amino acid substitutions that are compatible with biological function are understood to depend on the relative similarity of the amino acids, and particularly the side chains of those amino acids, as revealed by the hydrophobicity, hydrophilicity, charge, size, and other properties. A variant may be a nucleic acid sequence that is substantially identical over the full length of the full gene sequence or a fragment thereof. The nucleic acid sequence may be 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical over the full length of the gene sequence or a fragment thereof. A variant may be an amino acid sequence that is substantially identical over the full length of the amino acid sequence or fragment thereof. The amino acid sequence may be 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical over the full length of the amino acid sequence or a fragment thereof. “Vector” as used herein may mean a nucleic acid sequence containing an origin of replication. A vector may be a plasmid, bacteriophage, bacterial artificial chromosome or yeast artificial chromosome. A vector may be a DNA or RNA vector. A vector may be either a self-replicating extrachromosomal vector or a vector which integrates into a host genome. Docket No.206193-0136-00WO For the recitation of numeric ranges herein, each intervening number there between with the same degree of precision is explicitly contemplated. For example, for the range of 6-9, the numbers 7 and 8 are contemplated in addition to 6 and 9, and for the range 6.0-7.0, the number 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, and 7.0 are explicitly contemplated. Composition In some embodiments, the invention provides compositions that bind to a Streptococcus pneumoniae antigen, including, but not limited to, pneumococcal histidine triad protein D (PhtD). In some embodiments, the composition that binds PhtD is an antibody. The invention relates to a composition comprising a recombinant nucleic acid sequence encoding an antibody, a fragment thereof, a variant thereof, or a combination thereof. The composition, when administered to a subject in need thereof, can result in the generation of a synthetic antibody in the subject. The synthetic antibody can bind a target molecule (i.e., an antigen) present in the subject. Such binding can neutralize the antigen, block recognition of the antigen by another molecule, for example, a protein or nucleic acid, and elicit or induce an immune response to the antigen. In one embodiment, the composition comprises a nucleotide sequence encoding a synthetic antibody. In one embodiment, the composition comprises a nucleic acid molecule comprising a first nucleotide sequence encoding a first synthetic antibody and a second nucleotide sequence encoding a second synthetic antibody. In one embodiment, the nucleic acid molecule comprises a nucleotide sequence encoding a cleavage domain. In one embodiment, the nucleic acid molecule comprises a nucleotide sequence encoding an antibody to PhtD. In one embodiment, the nucleic acid molecule comprises a nucleotide sequence encoding a variable heavy chain region and a nucleotide sequence encoding a variable light chain region of an anti-PhtD antibody. In one embodiment, the invention provides a composition comprising a first nucleic acid molecule comprising a nucleotide sequence encoding a variable heavy chain region of an anti-PhtD antibody and a second nucleic acid molecule comprising a nucleotide sequence encoding a variable light chain region of an anti-PhtD antibody. Antibodies, including PhtD protein fragments, of the present invention include, in certain embodiments, antibody amino acid sequences disclosed herein encoded by Docket No.206193-0136-00WO any suitable polynucleotide, or any isolated or formulated antibody. Further, antibodies of the present disclosure comprise antibodies having the structural and / or functional features of anti- PhtD antibodies described herein. In one embodiment, the anti-PhtD antibody binds PhtD and, thereby partially or substantially alters at least one biological activity of the PhtD protein (e.g., receptor binding activity). Antibodies In some embodiments, the invention includes compositions comprising an antibody that specifically binds to PhtD (e.g., binding portion of an antibody). In one embodiment, the anti- PhtD antibody is a polyclonal antibody. In another embodiment, the anti- PhtD antibody is a monoclonal antibody. In some embodiments, the anti- PhtD antibody is a chimeric antibody. In further embodiments, the anti- PhtD antibody is a humanized antibody. The binding portion of an antibody comprises one or more fragments of an antibody that retain the ability to specifically bind to binding partner molecule (e.g., PhtD). It has been shown that the binding function of an antibody can be performed by fragments of a full-length antibody. Examples of binding fragments encompassed within the term “binding portion” of an antibody include (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CH1 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 CH1 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 molecules (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). Such single chain antibodies are also intended to be encompassed within the term “binding portion” of an antibody. These antibody fragments are obtained using conventional techniques known to those with skill in the art, and the fragments are screened for utility in the same manner as are intact antibodies. Binding portions can be produced by recombinant DNA techniques, or by enzymatic or chemical cleavage of intact immunoglobulins. Docket No.206193-0136-00WO The antibody may comprise a heavy chain and a light chain complementarity determining region (“CDR”) set, respectively interposed between a heavy chain and a light chain framework (“FR”) set which provide support to the CDRs and define the spatial relationship of the CDRs relative to each other. The CDR set may contain three hypervariable regions of a heavy or light chain V region. Proceeding from the N-terminus of a heavy or light chain, these regions are denoted as “CDR1,” “CDR2,” and “CDR3,” respectively. An antigen-binding site, therefore, may include six CDRs, comprising the CDR set from each of a heavy and a light chain V region. The antibody can be an immunoglobulin (Ig). The Ig can be, for example, IgA, IgM, IgD, IgE, and IgG. The immunoglobulin can include the heavy chain polypeptide and the light chain polypeptide. The heavy chain polypeptide of the immunoglobulin can include a VH region, a CH1 region, a hinge region, a CH2 region, and a CH3 region. The light chain polypeptide of the immunoglobulin can include a VL region and CL region. The antibody can be a polyclonal or monoclonal antibody. The antibody can be a chimeric antibody, a single chain antibody, an affinity matured antibody, a human antibody, a humanized antibody, or a fully human antibody. The humanized antibody can be an antibody from a non-human species that binds the desired antigen having one or more complementarity determining regions (CDRs) from the non-human species and framework regions from a human immunoglobulin molecule. As described herein, the antibody can be generated in the subject upon administration of the composition to the subject. The antibody may have a half-life within the subject. In some embodiments, the antibody may be modified to extend or shorten its half-life within the subject. Such modifications are described below in more detail. The antibody can be defucosylated. The antibody may be modified to reduce or prevent antibody-dependent enhancement (ADE) of disease associated with the antigen as described in more detail below. In one embodiment, the PhtD antibody comprises a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:9. In one embodiment, the PhtD antibody comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO:5 or SEQ ID NO:7. Given that certain of the monoclonal antibodies can bind to PhtD, the VH and VL sequences can be “mixed and matched” to create other anti- PhtD binding molecules of this disclosure. Binding of such “mixed and matched” antibodies can be tested using standard Docket No.206193-0136-00WO binding assays known in the art (e.g., immunoblot etc.). In some embodiments, when VH and VL chains are mixed and matched, a VH sequence from a particular VH / VL pairing is replaced with a structurally similar VH sequence. Likewise, preferably a VL sequence from a particular VH / VL pairing is replaced with a structurally similar VL sequence. Accordingly, in one embodiment, this disclosure provides an isolated monoclonal antibody, or binding portion thereof comprising: (a) a heavy chain amino acid sequence of SEQ ID NO:1; and (b) a light chain amino acid sequence of SEQ ID NO:5. In one embodiment, this disclosure provides an isolated monoclonal antibody, or binding portion thereof comprising: (a) a heavy chain amino acid sequence of SEQ ID NO:3 or SEQ ID NO: 9; and (b) a light chain amino acid sequence of SEQ ID NO:7. In one embodiment, anti-PhtD antibody comprises a heavy chain amino acid sequence having at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence as set forth in SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:9. In one embodiment, anti-PhtD antibody comprises a light chain amino acid sequence having at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence as set forth in SEQ ID NO:5 or SEQ ID NO:7. Extension of Antibody Half-Life The antibody may be modified to extend or shorten the half-life of the antibody in the subject. The modification may extend or shorten the half-life of the antibody in the serum of the subject. The modification may be present in a constant region of the antibody. The modification may be one or more amino acid substitutions in a constant region of the antibody that extend the half-life of the antibody as compared to a half-life of an antibody not containing the one or more amino acid substitutions. The modification may be one or more amino acid substitutions in the CH2 domain of the antibody that extend the half-life of the antibody as compared to a half-life of an antibody not containing the one or more amino acid substitutions. In some embodiments, the one or more amino acid substitutions in the constant region may include replacing a methionine residue in the constant region with a tyrosine residue, a serine residue in the constant region with a threonine residue, a threonine residue in the constant region with a glutamate residue, or any combination thereof, thereby extending the half-life of the antibody. Docket No.206193-0136-00WO In other embodiments, the one or more amino acid substitutions in the constant region may include replacing a methionine residue in the CH2 domain with a tyrosine residue, a serine residue in the CH2 domain with a threonine residue, a threonine residue in the CH2 domain with a glutamate residue, or any combination thereof, thereby extending the half-life of the antibody. Defucosylation The antibody may be an antibody that is not fucosylated (i.e., a defucosylated antibody or a non-fucosylated antibody), a fragment thereof, a variant thereof, or a combination thereof. Fucosylation includes the addition of the sugar fucose to a molecule, for example, the attachment of fucose to N-glycans, O-glycans and glycolipids. Accordingly, in a defucosylated antibody, fucose is not attached to the carbohydrate chains of the constant region. In turn, this lack of fucosylation may improve FcγRIIIa binding and antibody directed cellular cytotoxic (ADCC) activity by the antibody as compared to the fucosylated antibody. Therefore, in some embodiments, the non-fucosylated antibody may exhibit increased ADCC activity as compared to the fucosylated antibody. The antibody may be modified so as to prevent or inhibit fucosylation of the antibody. In some embodiments, such a modified antibody may exhibit increased ADCC activity as compared to the unmodified antibody. The modification may be in the heavy chain, light chain, or a combination thereof. The modification may be one or more amino acid substitutions in the heavy chain, one or more amino acid substitutions in the light chain, or a combination thereof. Reduced ADE Response The antibody may be modified to reduce or prevent antibody-dependent enhancement (ADE) of disease associated with the antigen, but still neutralize the antigen. In some embodiments, the antibody may be modified to include one or more amino acid substitutions that reduce or prevent binding of the antibody to FcyR1a. The one or more amino acid substitutions may be in the constant region of the antibody. Bispecific Antibody The antibody may be a bispecific antibody, a fragment thereof, a variant thereof, or a combination thereof. The bispecific antibody can bind or react with two Docket No.206193-0136-00WO antigens, for example, two of the antigens described below in more detail. The bispecific antibody can be comprised of fragments of two of the antibodies described herein, thereby allowing the bispecific antibody to bind or react with two desired target molecules, which may include the antigen, which is described below in more detail, a ligand, including a ligand for a receptor, a receptor, including a ligand-binding site on the receptor, a ligand-receptor complex, and a marker. The invention provides novel bispecific antibodies comprising a first antigen- binding site that specifically binds to a first target and a second antigen-binding site that specifically binds to a second target, with particularly advantageous properties such as producibility, stability, binding affinity, biological activity, specific targeting of certain T cells, targeting efficiency and reduced toxicity. In some instances, there are bispecific antibodies, wherein the bispecific antibody binds to the first target with high affinity and to the second target with low affinity. In other instances, there are bispecific antibodies, wherein the bispecific antibody binds to the first target with low affinity and to the second target with high affinity. In other instances, there are bispecific antibodies, wherein the bispecific antibody binds to the first target with a desired affinity and to the second target with a desired affinity. In one embodiment, the bispecific antibody is a bivalent antibody comprising a) a first light chain and a first heavy chain of an antibody specifically binding to a first antigen, and b) a second light chain and a second heavy chain of an antibody specifically binding to a second antigen. A bispecific antibody molecule according to the invention may have two binding sites of any desired specificity. In some embodiments, the binding site included in the Fab fragment is a binding site specific for a PhtD antigen. In some embodiments, the binding site included in the single chain Fv fragment is a binding site specific for a PhtD antigen. Bifunctional Antibody The antibody may be a bifunctional antibody, a fragment thereof, a variant thereof, or a combination thereof. The bifunctional antibody can bind or react with the antigen described below. The bifunctional antibody can also be modified to impart an additional functionality to the antibody beyond recognition of and binding to the antigen. Such a modification can include, but is not limited to, coupling to factor H or a fragment Docket No.206193-0136-00WO thereof. Factor H is a soluble regulator of complement activation and thus, may contribute to an immune response via complement-mediated lysis (CML). Antigen The synthetic antibody may be directed to the antigen or fragment or variant thereof. The antigen can be a nucleic acid sequence, an amino acid sequence, a polysaccharide or a combination thereof. The nucleic acid sequence can be DNA, RNA, cDNA, a variant thereof, a fragment thereof, or a combination thereof. The amino acid sequence can be a protein, a peptide, a variant thereof, a fragment thereof, or a combination thereof. The polysaccharide can be a nucleic acid encoded polysaccharide. The antigen can be from a virus. The antigen can be associated with bacterial infection. In one embodiment, the antigen can be associated with Streptococcus pneumoniae infection. In one embodiment, the antigen can be a PhtD antigen. In one embodiment, the antigen can be a fragment of a PhtD antigen. In one embodiment, a synthetic antibody of the invention targets two or more antigens. In one embodiment, at least one antigen of a bispecific antibody is selected from the antigens described herein. In one embodiment, the two or more antigens are selected from the antigens described herein. Generation of Synthetic Antibodies In Vitro and Ex Vivo In one embodiment, one or more synthetic antibody is generated in vitro or ex vivo. For example, in one embodiment, a nucleic acid encoding a synthetic antibody can be introduced and expressed in an in vitro or ex vivo cell. Methods of introducing and expressing genes into a cell are known in the art. In the context of an expression vector, the vector can be readily introduced into a host cell, e.g., mammalian, bacterial, yeast, or insect cell by any method in the art. For example, the expression vector can be transferred into a host cell by physical, chemical, or biological means. Physical methods for introducing a polynucleotide into a host cell include calcium phosphate precipitation, lipofection, particle bombardment, microinjection, electroporation, and the like. Methods for producing cells comprising vectors and / or exogenous nucleic acids are well-known in the art. See, for example, Sambrook et al. (2012, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York). A Docket No.206193-0136-00WO preferred method for the introduction of a polynucleotide into a host cell is calcium phosphate transfection. Biological methods for introducing a polynucleotide of interest into a host cell include the use of DNA and RNA vectors. Viral vectors, and especially retroviral vectors, have become the most widely used method for inserting genes into mammalian, e.g., human cells. Other viral vectors can be derived from lentivirus, poxviruses, herpes simplex virus I, adenoviruses and adeno-associated viruses, and the like. See, for example, U.S. Pat. Nos. 5,350,674 and 5,585,362. Chemical means for introducing a polynucleotide into a host cell include colloidal dispersion systems, such as macromolecule complexes, nanocapsules, microspheres, beads, and lipid-based systems including oil-in-water emulsions, micelles, mixed micelles, and liposomes. An exemplary colloidal system for use as a delivery vehicle in vitro and in vivo is a liposome (e.g., an artificial membrane vesicle). In the case where a non-viral delivery system is utilized, an exemplary delivery vehicle is a liposome or lipid nanoparticle. The use of lipid formulations is contemplated for the introduction of the nucleic acids into a host cell (in vitro, ex vivo or in vivo). In another aspect, the nucleic acid may be associated with a lipid. The nucleic acid associated with a lipid may be encapsulated in the aqueous interior of a liposome, interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the oligonucleotide, entrapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid. Lipid, lipid / DNA or lipid / expression vector associated compositions are not limited to any particular structure in solution. For example, they may be present in a bilayer structure, as micelles, or with a “collapsed” structure. They may also simply be interspersed in a solution, possibly forming aggregates that are not uniform in size or shape. Lipids are fatty substances which may be naturally occurring or synthetic lipids. For example, lipids include the fatty droplets that naturally occur in the cytoplasm as well as the class of compounds which contain long-chain aliphatic hydrocarbons and their derivatives, such as fatty acids, alcohols, amines, amino alcohols, and aldehydes. Docket No.206193-0136-00WO Recombinant Nucleic Acid Sequence In some aspects, the composition can comprise a recombinant nucleic acid sequence. The recombinant nucleic acid sequence can encode the antibody, a fragment thereof, a variant thereof, or a combination thereof. The recombinant nucleic acid sequence can be a heterologous nucleic acid sequence. The recombinant nucleic acid sequence can include at least one heterologous nucleic acid sequence or one or more heterologous nucleic acid sequences. The recombinant nucleic acid sequence can be an optimized nucleic acid sequence. Such optimization can increase or alter the immunogenicity of the antibody. Optimization can also improve transcription and / or translation. Optimization can include one or more of the following: low GC content leader sequence to increase transcription; mRNA stability and codon optimization; addition of a kozak sequence (e.g., GCC ACC) for increased translation; addition of an immunoglobulin (Ig) leader sequence encoding a signal peptide; and eliminating to the extent possible cis-acting sequence motifs (i.e., internal TATA boxes). In one embodiment, the anti- PhtD antibody comprises a DMAb encoded by a single plasmid which comprises sequences encoding both the heavy and light chains of the antibody. In one embodiment, the DMAb comprises a nucleic acid molecule encoding an amino acid sequence selected from SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7 or SEQ ID NO:9, an amino acid sequence having at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence as set forth in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7 or SEQ ID NO:9, or a fragment comprising at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% of the full length of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7 or SEQ ID NO:9. In one embodiment, the invention relates to a nucleotide sequence encoding an anti- PhtD antibody comprises a nucleic acid sequence encoding a heavy chain amino acid sequence having at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence as set forth in SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:9. In one embodiment, the nucleotide sequence encoding an anti-PhtD antibody comprises a codon optimized nucleic acid sequence encoding a fragment comprising at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% of the full length of an amino acid sequence as set forth in SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:9, wherein the sequence encodes each of the CDRs of SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:9. Docket No.206193-0136-00WO In one embodiment, the invention relates to a nucleotide sequence encoding a heavy chain of an anti-PhtD antibody comprising a nucleotide sequence having at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, or SEQ ID NO:15. In one embodiment, the nucleotide sequence encoding an anti- PhtD antibody comprises a codon optimized nucleic acid sequence comprising at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% of the full length of a nucleotide sequence as set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, or SEQ ID NO:15, wherein the sequence encodes each of the CDRs of SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:9. In one embodiment, the invention relates to a nucleotide sequence encoding an anti- PhtD antibody comprises a nucleic acid sequence encoding a light chain amino acid sequence having at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence as set forth in SEQ ID NO:5 or SEQ ID NO:7. In one embodiment, the nucleotide sequence encoding an anti- PhtD antibody comprises a codon optimized nucleic acid sequence encoding a fragment comprising at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% of the full length of an amino acid sequence as set forth in SEQ ID NO:5 or SEQ ID NO: 7, wherein the sequence encodes each of the CDRs of SEQ ID NO: 5 or SEQ ID NO: 7. In one embodiment, the nucleic acid sequence encoding a light chain amino acid sequence has at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:13, or SEQ ID NO:14. In one embodiment, the nucleotide sequence encoding an anti- PhtD antibody comprises a codon optimized nucleic acid sequence comprising at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% of the full length of a nucleotide sequence as set forth in SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:13, or SEQ ID NO:14, wherein the sequence encodes each of the CDRs of SEQ ID NO: 5, or SEQ ID NO:7. In one embodiment, the nucleotide sequence encoding an anti- PhtD antibody comprises an RNA sequence transcribed from a DNA sequence encoding a heavy chain amino acid sequence having at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence as set forth in SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:9, or a combination thereof. In one embodiment, the nucleotide sequence encoding an anti- PhtD antibody comprises an RNA sequence transcribed from a DNA sequence encoding a heavy chain amino acid sequence as set forth in SEQ ID NO:1, SEQ ID NO:3, or SEQ ID Docket No.206193-0136-00WO NO:9,. In one embodiment, the nucleotide sequence encoding an anti- PhtD antibody comprises an RNA sequence transcribed from a DNA sequence encoding a fragment comprising at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% of the full length of SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:9,. In one embodiment, the nucleotide sequence encoding an anti- PhtD antibody comprises an RNA sequence transcribed from a DNA sequence encoding a heavy chain amino acid sequence having at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to a nucleotide sequence as set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO:15, or a combination thereof. In one embodiment, the nucleotide sequence encoding an anti- PhtD antibody comprises an RNA sequence transcribed from a DNA sequence encoding a heavy chain comprising a nucleotide sequence as set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO:15. In one embodiment, the nucleotide sequence encoding an anti- PhtD antibody comprises an RNA sequence transcribed from a DNA sequence comprising at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% of the full length of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO:15. In one embodiment, the nucleotide sequence encoding an anti- PhtD antibody comprises an RNA sequence transcribed from a DNA sequence encoding a light chain amino acid sequence having at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence as set forth in SEQ ID NO: 5, or a combination thereof. In one embodiment, the nucleotide sequence encoding an anti- PhtD antibody comprises an RNA sequence transcribed from a DNA sequence encoding a light chain amino acid sequence as set forth in SEQ ID NO: 5. In one embodiment, the nucleotide sequence encoding an anti- PhtD antibody comprises an RNA sequence transcribed from a DNA sequence encoding a fragment comprising at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% of the full length of SEQ ID NO: 5. In one embodiment, the nucleotide sequence encoding an anti- PhtD antibody comprises an RNA sequence transcribed from a DNA sequence encoding a light chain amino acid sequence having at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to a nucleotide sequence as set forth in SEQ ID NO:5, SEQ ID NO:13, or SEQ ID NO:14, or a combination thereof. In one embodiment, the nucleotide sequence encoding an anti- PhtD antibody comprises an RNA sequence transcribed from a DNA sequence encoding a light chain comprising a nucleotide sequence as set forth in SEQ ID NO:5, SEQ ID NO:13, or Docket No.206193-0136-00WO SEQ ID NO:14. In one embodiment, the nucleotide sequence encoding an anti- PhtD antibody comprises an RNA sequence transcribed from a DNA sequence encoding a light chain comprising a nucleotide sequence comprising at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% of the full length of SEQ ID NO:5, SEQ ID NO:13, or SEQ ID NO:14. In one embodiment, the nucleotide sequence encoding an anti- PhtD antibody comprises an RNA sequence transcribed from a DNA sequence encoding a heavy chain, a light chain or a combination thereof of an antibody of the invention. In one embodiment, the invention relates to a combination of a first nucleic acid molecule encoding a heavy chain of an anti- PhtD antibody, and a second nucleic acid molecule encoding a light chain of an anti- PhtD antibody. In one embodiment, the first nucleic acid molecule is a first plasmid comprising a nucleotide sequence encoding a heavy chain of an anti- PhtD antibody and the second nucleic acid molecule is a second plasmid encoding a light chain of an anti- PhtD antibody. In one embodiment, the first nucleic acid molecule encoding a heavy chain of an anti- PhtD antibody encodes SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:9, or an amino acid sequence having at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence as set forth in SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:9, or a fragment comprising at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% of the full length of SEQ ID NO:1, SEQ ID NO:3, or SEQ ID NO:9. In one embodiment, the first nucleic acid molecule encoding a heavy chain of an anti- PhtD antibody comprises SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:15, or a nucleotide sequence having at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:15, or a fragment comprising at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% of the full length of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:15. In one embodiment, the second nucleic acid molecule encoding a light chain of an anti- PhtD antibody encodes SEQ ID NO: 5, or SEQ ID NO: 7, an amino acid sequence having at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence as set forth in SEQ ID NO: 5, or SEQ ID NO: 7or a fragment comprising at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% of the full length of SEQ ID NO: 5, or SEQ ID NO: 7. Docket No.206193-0136-00WO In one embodiment, the second nucleic acid molecule encoding a light chain of an anti- PhtD antibody comprises SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:13, or SEQ ID NO:14, or a nucleotide sequence having at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:13, or SEQ ID NO:14,, or a fragment comprising at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% of the full length of SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:13, or SEQ ID NO:14. In one embodiment, the invention relates to a combination of a first nucleic acid molecule comprising a nucleotide sequence of SEQ ID NO:2, encoding a heavy chain amino acid sequence, and a second nucleic acid molecule comprising a nucleotide sequence of SEQ ID NO:6 or SEQ ID NO: 13, encoding a light chain amino acid sequence. In one embodiment, the invention relates to a combination of a first nucleic acid molecule comprising a nucleotide sequence of SEQ ID NO:4, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO: 15, encoding a heavy chain amino acid sequence, and a second nucleic acid molecule comprising a nucleotide sequence of SEQ ID NO:8 or SEQ ID NO: 14, encoding a light chain amino acid sequence. In one embodiment, the nucleic acid molecule is a single plasmid encoding a heavy and light chain of a DMAb. Heavy Chain Polypeptide The recombinant nucleic acid sequence construct can include the heterologous nucleic acid encoding the heavy chain polypeptide, a fragment thereof, a variant thereof, or a combination thereof. The heavy chain polypeptide can include a variable heavy chain (VH) region and / or at least one constant heavy chain (CH) region. The at least one constant heavy chain region can include a constant heavy chain region 1 (CH1), a constant heavy chain region 2 (CH2), and a constant heavy chain region 3 (CH3), and / or a hinge region. In some embodiments, the heavy chain polypeptide can include a VH region and a CH1 region. In other embodiments, the heavy chain polypeptide can include a VH region, a CH1 region, a hinge region, a CH2 region, and a CH3 region. The heavy chain polypeptide can include a complementarity determining region (“CDR”) set. The CDR set can contain three hypervariable regions of the VH region. Proceeding from N-terminus of the heavy chain polypeptide, these CDRs are denoted “CDR1,” “CDR2,” and “CDR3,” respectively. CDR1, CDR2, and CDR3 of the heavy chain polypeptide can contribute to binding or recognition of the antigen. Docket No.206193-0136-00WO Light Chain Polypeptide The recombinant nucleic acid sequence construct can include the heterologous nucleic acid sequence encoding the light chain polypeptide, a fragment thereof, a variant thereof, or a combination thereof. The light chain polypeptide can include a variable light chain (VL) region and / or a constant light chain (CL) region. The light chain polypeptide can include a complementarity determining region (“CDR”) set. The CDR set can contain three hypervariable regions of the VL region. Proceeding from N-terminus of the light chain polypeptide, these CDRs are denoted “CDR1,” “CDR2,” and “CDR3,” respectively. CDR1, CDR2, and CDR3 of the light chain polypeptide can contribute to binding or recognition of the antigen. Promoter The recombinant nucleic acid sequence construct can include one or more promoters. The one or more promoters may be any promoter that is capable of driving gene expression and regulating gene expression. Such a promoter is a cis-acting sequence element required for transcription via a DNA dependent RNA polymerase. Selection of the promoter used to direct gene expression depends on the particular application. The promoter may be positioned about the same distance from the transcription start in the recombinant nucleic acid sequence construct as it is from the transcription start site in its natural setting. However, variation in this distance may be accommodated without loss of promoter function. The promoter may be operably linked to the heterologous nucleic acid sequence encoding the heavy chain polypeptide and / or light chain polypeptide. The promoter may be a promoter shown effective for expression in eukaryotic cells. The promoter operably linked to the coding sequence may be a CMV promoter, a promoter from simian virus 40 (SV40), such as SV40 early promoter and SV40 later promoter, a mouse mammary tumor virus (MMTV) promoter, a human immunodeficiency virus (HIV) promoter such as the bovine immunodeficiency virus (BIV) long terminal repeat (LTR) promoter, a Moloney virus promoter, an avian leukosis virus (ALV) promoter, a cytomegalovirus (CMV) promoter such as the CMV immediate early promoter, Epstein Barr virus (EBV) promoter, or a Rous sarcoma virus (RSV) promoter. The promoter may also be a promoter from a human gene such as human actin, human myosin, human hemoglobin, human muscle creatine, human polyhedrin, or human metalothionein. Docket No.206193-0136-00WO The promoter can be a constitutive promoter or an inducible promoter, which initiates transcription only when the host cell is exposed to some particular external stimulus. In the case of a multicellular organism, the promoter can also be specific to a particular tissue or organ or stage of development. The promoter may also be a tissue specific promoter, such as a muscle or skin specific promoter, natural or synthetic. Examples of such promoters are described in US patent application publication no. US20040175727, the contents of which are incorporated herein in its entirety. The promoter can be associated with an enhancer. The enhancer can be located upstream of the coding sequence. The enhancer may be human actin, human myosin, human hemoglobin, human muscle creatine or a viral enhancer such as one from CMV, FMDV, RSV or EBV. Polynucleotide function enhances are described in U.S. Patent Nos. 5,593,972, 5,962,428, and W094 / 016737, the contents of each are fully incorporated by reference. Intron The recombinant nucleic acid sequence construct can include one or more introns. Each intron can include functional splice donor and acceptor sites. The intron can include an enhancer of splicing. The intron can include one or more signals required for efficient splicing. Transcription Termination Region The recombinant nucleic acid sequence construct can include one or more transcription termination regions. The transcription termination region can be downstream of the coding sequence to provide for efficient termination. The transcription termination region can be obtained from the same gene as the promoter described above or can be obtained from one or more different genes. Initiation Codon The recombinant nucleic acid sequence construct can include one or more initiation codons. The initiation codon can be located upstream of the coding sequence. The initiation codon can be in frame with the coding sequence. The initiation codon can be associated with one or more signals required for efficient translation initiation, for example, but not limited to, a ribosome binding site. Docket No.206193-0136-00WO Termination Codon The recombinant nucleic acid sequence construct can include one or more termination or stop codons. The termination codon can be downstream of the coding sequence. The termination codon can be in frame with the coding sequence. The termination codon can be associated with one or more signals required for efficient translation termination. Polyadenylation Signal The recombinant nucleic acid sequence construct can include one or more polyadenylation signals. The polyadenylation signal can include one or more signals required for efficient polyadenylation of the transcript. The polyadenylation signal can be positioned downstream of the coding sequence. The polyadenylation signal may be a SV40 polyadenylation signal, LTR polyadenylation signal, bovine growth hormone (bGH) polyadenylation signal, human growth hormone (hGH) polyadenylation signal, or human β- globin polyadenylation signal. The SV40 polyadenylation signal may be a polyadenylation signal from a pCEP4 plasmid (Invitrogen, San Diego, CA). Leader Sequence The recombinant nucleic acid sequence construct can include one or more leader sequences. The leader sequence can encode a signal peptide. The signal peptide can be an immunoglobulin (Ig) signal peptide, for example, but not limited to, an IgG signal peptide and a IgE signal peptide. Expression from the Recombinant Nucleic Acid Sequence Construct The recombinant nucleic acid sequence construct can include, amongst the one or more components, the heterologous nucleic acid sequence encoding the heavy chain polypeptide and / or the heterologous nucleic acid sequence encoding the light chain polypeptide. Accordingly, the recombinant nucleic acid sequence construct can facilitate expression of the heavy chain polypeptide and / or the light chain polypeptide. Upon expression, for example, but not limited to, in a cell, organism, or mammal, the heavy chain polypeptide and the light chain polypeptide can assemble into the synthetic antibody. In particular, the heavy chain polypeptide and the light chain polypeptide can interact with one another such that assembly results in the synthetic antibody being capable of binding the antigen. In other embodiments, the heavy chain polypeptide and the Docket No.206193-0136-00WO light chain polypeptide can interact with one another such that assembly results in the synthetic antibody being more immunogenic as compared to an antibody not assembled as described herein. In still other embodiments, the heavy chain polypeptide and the light chain polypeptide can interact with one another such that assembly results in the synthetic antibody being capable of eliciting or inducing an immune response against the antigen. Vector The recombinant nucleic acid sequence construct described above can be placed in one or more vectors. The one or more vectors can contain an origin of replication. The one or more vectors can be a plasmid, bacteriophage, bacterial artificial chromosome or yeast artificial chromosome. The one or more vectors can be either a self-replication extra chromosomal vector, or a vector which integrates into a host genome. The one or more vectors can be a heterologous expression construct, which is generally a plasmid that is used to introduce a specific gene into a target cell. Once the expression vector is inside the cell, the antibody or antibody fragment that is encoded by the recombinant nucleic acid sequence construct is produced by the cellular-transcription and translation machinery ribosomal complexes. The one or more vectors can express large amounts of stable messenger RNA, and therefore proteins. Expression Vector The one or more vectors can be a circular plasmid or a linear nucleic acid. The circular plasmid and linear nucleic acid are capable of directing expression of a particular nucleotide sequence in an appropriate subject cell. The one or more vectors comprising the recombinant nucleic acid sequence construct may be chimeric, meaning that at least one of its components is heterologous with respect to at least one of its other components. Plasmid The one or more vectors can be a plasmid. The plasmid may be useful for transfecting cells with the recombinant nucleic acid sequence construct. The plasmid may be useful for introducing the recombinant nucleic acid sequence construct into the subject. The plasmid may also comprise a regulatory sequence, which may be well suited for gene expression in a cell into which the plasmid is administered. Docket No.206193-0136-00WO The plasmid may also comprise a mammalian origin of replication in order to maintain the plasmid extrachromosomally and produce multiple copies of the plasmid in a cell. The plasmid may be pVAX1, pCEP4 or pREP4 from Invitrogen (San Diego, CA), which may comprise the Epstein Barr virus origin of replication and nuclear antigen EBNA-1 coding region, which may produce high copy episomal replication without integration. The backbone of the plasmid may be pAV0242. The plasmid may be a replication defective adenovirus type 5 (Ad5) plasmid. The plasmid may be pSE420 (Invitrogen, San Diego, Calif.), which may be used for protein production in Escherichia coli (E.coli). The plasmid may also be p YES2 (Invitrogen, San Diego, Calif.), which may be used for protein production in Saccharomyces cerevisiae strains of yeast. The plasmid may also be of the MAXBAC™ complete baculovirus expression system (Invitrogen, San Diego, Calif.), which may be used for protein production in insect cells. The plasmid may also be pcDNAI or pcDNA3 (Invitrogen, San Diego, Calif.), which may be used for protein production in mammalian cells such as Chinese hamster ovary (CHO) cells. Circular and Linear Vector The one or more vectors may be circular plasmid, which may transform a target cell by integration into the cellular genome or exist extrachromosomally (e.g., autonomous replicating plasmid with an origin of replication). The vector can be pVAX, pcDNA3.0, or provax, or any other expression vector capable of expressing the antibody or antibody fragment encoded by the recombinant nucleic acid sequence construct. Also provided herein is a linear nucleic acid, or linear expression cassette (“LEC”), that is capable of being efficiently delivered to a subject via electroporation and expressing the antibody or antibody fragment encoded by the recombinant nucleic acid sequence construct. The LEC may be any linear DNA devoid of any phosphate backbone. The LEC may not contain any antibiotic resistance genes and / or a phosphate backbone. The LEC may not contain other nucleic acid sequences unrelated to the desired gene expression. The LEC may be derived from any plasmid capable of being linearized. The plasmid may be capable of expressing the antibody or antibody fragment encoded by the recombinant nucleic acid sequence construct. The plasmid can be pNP (Puerto Rico / 34) or pM2 (New Caledonia / 99). The plasmid may be WLV009, pVAX, pcDNA3.0, or provax, or Docket No.206193-0136-00WO any other expression vector capable of expressing the antibody or antibody fragment encoded by the recombinant nucleic acid sequence construct. The LEC can be pcrM2. The LEC can be pcrNP. pcrNP and pcrMR can be derived from pNP (Puerto Rico / 34) and pM2 (New Caledonia / 99), respectively. Viral Vectors In one embodiment, viral vectors are provided herein which are capable of delivering a nucleic acid of the invention to a cell. The expression vector may be provided to a cell in the form of a viral vector. Viral vector technology is well known in the art and is described, for example, in Sambrook et al. (2001), and in Ausubel et al. (1997), and in other virology and molecular biology manuals. Viruses, which are useful as vectors include, but are not limited to, retroviruses, adenoviruses, adeno-associated viruses, herpes viruses, and lentiviruses. In general, a suitable vector contains an origin of replication functional in at least one organism, a promoter sequence, convenient restriction endonuclease sites, and one or more selectable markers. (See, e.g., WO 01 / 96584; WO 01 / 29058; and U.S. Pat. No. 6,326,193. Viral vectors, and especially retroviral vectors, have become the most widely used method for inserting genes into mammalian, e.g., human cells. Other viral vectors can be derived from lentivirus, poxviruses, herpes simplex virus I, adenoviruses and adeno- associated viruses, and the like. See, for example, U.S. Pat. Nos.5,350,674 and 5,585,362. Nanoparticle Formulations In one embodiment, the composition of the invention may comprise a nanoparticle, including but not limited to a lipid nanoparticle (LNP), comprising a PhtD antibody of the invention, or a LNP comprising a nucleic acid encoding a PhtD antibody of the invention. In some embodiments, the composition comprises or encodes all or part of a PhtD antigen binding molecule of the invention, or an immunogenically functional equivalent thereof. In some embodiments, the composition comprises an mRNA molecule that encodes all or part of a PhtD antigen binding molecule of the invention. In one embodiment, the immunogenic composition of the invention may comprise a composition comprising a combination of PhtD antibodies of the invention, or a LNP comprising one or more nucleic acid molecules encoding a combination of PhtD antibodies of the invention. In one embodiment, the immunogenic composition of the invention may comprise a composition comprising a combination of LNP, wherein the Docket No.206193-0136-00WO combination of LNP comprises one or more nucleic acid molecules encoding a combination of PhtD antibodies of the invention. In one embodiment, the LNP comprises or encapsulates an RNA molecule encoding at least one amino acid sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, or SEQ ID NO:9, or a fragment or variant thereof. In one embodiment, the LNP comprises or encapsulates an RNA molecule comprising a nucleotide sequence corresponding to, or transcribed from SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, or SEQ ID NO:15, or a fragment or variant thereof. In one embodiment, the invention provides a combination of LNPs comprising or encapsulating a combination of RNA molecules encoding an anti- PhtD antibody. In some embodiments the combination of LNPs comprises a first nucleic acid molecule encoding a heavy chain of an anti- PhtD antibody encoding SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:9, and a second nucleic acid molecule encoding a light chain of an anti-PhtD antibody encoding SEQ ID NO:5, or SEQ ID NO:7, or a fragment thereof comprising at least the variable region thereof. In one embodiment, the invention relates to a combination of LNPs comprising or encapsulating a combination of at least two RNA molecules encoding the combination of the heavy chain and light chain of the synthetic antibody of the invention or fragments or variants thereof. In one embodiment, the composition further comprises one or more additional immunostimulatory agents. Immunostimulatory agents include, but are not limited to, an additional antigen or antigen binding molecule, an immunomodulator, or an adjuvant. Arrangement of the Recombinant Nucleic Acid Sequence Construct As described above, the recombinant nucleic acid sequence can include one or more recombinant nucleic acid sequence constructs, in which each recombinant nucleic acid sequence construct can include one or more components. The one or more components are described in detail above. The one or more components, when included in the recombinant nucleic acid sequence construct, can be arranged in any order relative to one another. In some embodiments, the one or more components can be arranged in the recombinant nucleic acid sequence construct as described below. Docket No.206193-0136-00WO Arrangement 1 In one arrangement, a first recombinant nucleic acid sequence construct can include the heterologous nucleic acid sequence encoding the heavy chain polypeptide and a second recombinant nucleic acid sequence construct can include the heterologous nucleic acid sequence encoding the light chain polypeptide. The first recombinant nucleic acid sequence construct can be placed in a vector. The second recombinant nucleic acid sequence construct can be placed in a second or separate vector. Placement of the recombinant nucleic acid sequence construct into the vector is described in more detail below. The first recombinant nucleic acid sequence construct can also include the promoter, intron, transcription termination region, initiation codon, termination codon, and / or polyadenylation signal. The first recombinant nucleic acid sequence construct can further include the leader sequence, in which the leader sequence is located upstream (or 5’) of the heterologous nucleic acid sequence encoding the heavy chain polypeptide. Accordingly, the signal peptide encoded by the leader sequence can be linked by a peptide bond to the heavy chain polypeptide. The second recombinant nucleic acid sequence construct can also include the promoter, initiation codon, termination codon, and polyadenylation signal. The second recombinant nucleic acid sequence construct can further include the leader sequence, in which the leader sequence is located upstream (or 5’) of the heterologous nucleic acid sequence encoding the light chain polypeptide. Accordingly, the signal peptide encoded by the leader sequence can be linked by a peptide bond to the light chain polypeptide. Accordingly, one example of arrangement 1 can include the first vector (and thus first recombinant nucleic acid sequence construct) encoding the heavy chain polypeptide that includes VH and CH1, and the second vector (and thus second recombinant nucleic acid sequence construct) encoding the light chain polypeptide that includes VL and CL. A second example of arrangement 1 can include the first vector (and thus first recombinant nucleic acid sequence construct) encoding the heavy chain polypeptide that includes VH, CH1, hinge region, CH2, and CH3, and the second vector (and thus second recombinant nucleic acid sequence construct) encoding the light chain polypeptide that includes VL and CL. Arrangement 2 In a second arrangement, the recombinant nucleic acid sequence construct can include the heterologous nucleic acid sequence encoding the heavy chain polypeptide and the Docket No.206193-0136-00WO heterologous nucleic acid sequence encoding the light chain polypeptide. The heterologous nucleic acid sequence encoding the heavy chain polypeptide can be positioned upstream (or 5’) of the heterologous nucleic acid sequence encoding the light chain polypeptide. Alternatively, the heterologous nucleic acid sequence encoding the light chain polypeptide can be positioned upstream (or 5’) of the heterologous nucleic acid sequence encoding the heavy chain polypeptide. The recombinant nucleic acid sequence construct can be placed in the vector as described in more detail below. The recombinant nucleic acid sequence construct can include the heterologous nucleic acid sequence encoding the protease cleavage site and / or the linker sequence. If included in the recombinant nucleic acid sequence construct, the heterologous nucleic acid sequence encoding the protease cleavage site can be positioned between the heterologous nucleic acid sequence encoding the heavy chain polypeptide and the heterologous nucleic acid sequence encoding the light chain polypeptide. Accordingly, the protease cleavage site allows for separation of the heavy chain polypeptide and the light chain polypeptide into distinct polypeptides upon expression. In other embodiments, if the linker sequence is included in the recombinant nucleic acid sequence construct, then the linker sequence can be positioned between the heterologous nucleic acid sequence encoding the heavy chain polypeptide and the heterologous nucleic acid sequence encoding the light chain polypeptide. The recombinant nucleic acid sequence construct can also include the promoter, intron, transcription termination region, initiation codon, termination codon, and / or polyadenylation signal. The recombinant nucleic acid sequence construct can include one or more promoters. The recombinant nucleic acid sequence construct can include two promoters such that one promoter can be associated with the heterologous nucleic acid sequence encoding the heavy chain polypeptide and the second promoter can be associated with the heterologous nucleic acid sequence encoding the light chain polypeptide. In still other embodiments, the recombinant nucleic acid sequence construct can include one promoter that is associated with the heterologous nucleic acid sequence encoding the heavy chain polypeptide and the heterologous nucleic acid sequence encoding the light chain polypeptide. The recombinant nucleic acid sequence construct can further include two leader sequences, in which a first leader sequence is located upstream (or 5’) of the heterologous nucleic acid sequence encoding the heavy chain polypeptide and a second leader sequence is located upstream (or 5’) of the heterologous nucleic acid sequence Docket No.206193-0136-00WO encoding the light chain polypeptide. Accordingly, a first signal peptide encoded by the first leader sequence can be linked by a peptide bond to the heavy chain polypeptide and a second signal peptide encoded by the second leader sequence can be linked by a peptide bond to the light chain polypeptide. Accordingly, one example of arrangement 2 can include the vector (and thus recombinant nucleic acid sequence construct) encoding the heavy chain polypeptide that includes VH and CH1, and the light chain polypeptide that includes VL and CL, in which the linker sequence is positioned between the heterologous nucleic acid sequence encoding the heavy chain polypeptide and the heterologous nucleic acid sequence encoding the light chain polypeptide. A second example of arrangement of 2 can include the vector (and thus recombinant nucleic acid sequence construct) encoding the heavy chain polypeptide that includes VH and CH1, and the light chain polypeptide that includes VL and CL, in which the heterologous nucleic acid sequence encoding the protease cleavage site is positioned between the heterologous nucleic acid sequence encoding the heavy chain polypeptide and the heterologous nucleic acid sequence encoding the light chain polypeptide. A third example of arrangement 2 can include the vector (and thus recombinant nucleic acid sequence construct) encoding the heavy chain polypeptide that includes VH, CH1, hinge region, CH2, and CH3, and the light chain polypeptide that includes VL and CL, in which the linker sequence is positioned between the heterologous nucleic acid sequence encoding the heavy chain polypeptide and the heterologous nucleic acid sequence encoding the light chain polypeptide. A forth example of arrangement of 2 can include the vector (and thus recombinant nucleic acid sequence construct) encoding the heavy chain polypeptide that includes VH, CH1, hinge region, CH2, and CH3, and the light chain polypeptide that includes VL and CL, in which the heterologous nucleic acid sequence encoding the protease cleavage site is positioned between the heterologous nucleic acid sequence encoding the heavy chain polypeptide and the heterologous nucleic acid sequence encoding the light chain polypeptide. Excipients and Other Components of the Composition The composition may further comprise a pharmaceutically acceptable excipient. The pharmaceutically acceptable excipient can be functional molecules such as Docket No.206193-0136-00WO vehicles, carriers, or diluents. The pharmaceutically acceptable excipient can be a transfection facilitating agent, which can include surface active agents, such as immune- stimulating complexes (ISCOMS), Freunds incomplete adjuvant, LPS analog including monophosphoryl lipid A, muramyl peptides, quinone analogs, vesicles such as squalene and squalene, hyaluronic acid, lipids, liposomes, calcium ions, viral proteins, polyanions, polycations, or nanoparticles, or other known transfection facilitating agents. The transfection facilitating agent is a polyanion, polycation, including poly- L-glutamate (LGS), or lipid. The transfection facilitating agent is poly-L-glutamate, and the poly-L-glutamate may be present in the composition at a concentration less than 6 mg / ml. The transfection facilitating agent may also include surface active agents such as immune- stimulating complexes (ISCOMS), Freunds incomplete adjuvant, LPS analog including monophosphoryl lipid A, muramyl peptides, quinone analogs and vesicles such as squalene and squalene, and hyaluronic acid may also be used administered in conjunction with the composition. The composition may also include a transfection facilitating agent such as lipids, liposomes, including lecithin liposomes or other liposomes known in the art, as a DNA-liposome mixture (see for example W09324640), calcium ions, viral proteins, polyanions, polycations, or nanoparticles, or other known transfection facilitating agents. The transfection facilitating agent is a polyanion, polycation, including poly-L-glutamate (LGS), or lipid. Concentration of the transfection agent in the vaccine is less than 4 mg / ml, less than 2 mg / ml, less than 1 mg / ml, less than 0.750 mg / ml, less than 0.500 mg / ml, less than 0.250 mg / ml, less than 0.100 mg / ml, less than 0.050 mg / ml, or less than 0.010 mg / ml. The composition may further comprise a genetic facilitator agent as described in U.S. Serial No.021,579 filed April 1, 1994, which is fully incorporated by reference. The composition may comprise DNA at quantities of from about 1 nanogram to 100 milligrams; about 1 microgram to about 10 milligrams; or preferably about 0.1 microgram to about 10 milligrams; or more preferably about 1 milligram to about 2 milligram. In some preferred embodiments, composition according to the present invention comprises about 5 nanogram to about 1000 micrograms of DNA. In some preferred embodiments, composition can contain about 10 nanograms to about 800 micrograms of DNA. In some preferred embodiments, the composition can contain about 0.1 to about 500 micrograms of DNA. In some preferred embodiments, the composition can contain about 1 to about 350 micrograms of DNA. In some preferred embodiments, the composition can contain about 25 to about 250 micrograms, from about 100 to about 200 microgram, from Docket No.206193-0136-00WO about 1 nanogram to 100 milligrams; from about 1 microgram to about 10 milligrams; from about 0.1 microgram to about 10 milligrams; from about 1 milligram to about 2 milligram, from about 5 nanogram to about 1000 micrograms, from about 10 nanograms to about 800 micrograms, from about 0.1 to about 500 micrograms, from about 1 to about 350 micrograms, from about 25 to about 250 micrograms, from about 100 to about 200 microgram of DNA. The composition can be formulated according to the mode of administration to be used. An injectable pharmaceutical composition can be sterile, pyrogen free and particulate free. An isotonic formulation or solution can be used. Additives for isotonicity can include sodium chloride, dextrose, mannitol, sorbitol, and lactose. The composition can comprise a vasoconstriction agent. The isotonic solutions can include phosphate buffered saline. The composition can further comprise stabilizers including gelatin and albumin. The stabilizers can allow the formulation to be stable at room or ambient temperature for extended periods of time, including LGS or polycations or polyanions. Method of Treatment Also provided herein is a method of treating, protecting against, and / or preventing disease in a subject in need thereof by administering a synthetic antibody or nucleic acid molecule encoding the synthetic antibody to the subject. The method can include administering the composition to the subject. Administration of the composition to the subject can be done using the method of delivery described above. In certain embodiments, the invention provides a method of treating protecting against, and / or preventing a bacterial infection. In certain embodiments, the invention provides a method of treating protecting against, and / or preventing Streptococcus pneumoniae infection. The synthetic antibody can bind to or react with the antigen. Such binding can neutralize an antigen, block recognition of the antigen by another molecule, for example, a protein or nucleic acid, and elicit or induce an immune response to the antigen, thereby treating, protecting against, and / or preventing the disease associated with the antigen in the subject. The composition dose can be between 1 μg to 10 mg active component / kg body weight / time, and can be 20 μg to 10 mg component / kg body weight / time. The composition can be administered every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, Docket No.206193-0136-00WO 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or 31 days. The number of composition doses for effective treatment can be 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. The composition of the invention can treat, prevent and / or protect against any disease, disorder, or condition associated with a bacterial activity. In certain embodiments, the composition can treat, prevent, and or / protect against bacterial infection. In certain embodiments, the composition can treat, prevent, and or / protect against Streptococcus pneumoniae infection. The synthetic antibody can treat, prevent, and / or protect against disease in the subject administered the composition. The synthetic antibody by binding the antigen can treat, prevent, and / or protect against disease in the subject administered the composition. The synthetic antibody can promote survival of the disease in the subject administered the composition. The synthetic antibody can provide at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% survival of the disease in the subject administered the composition. In other embodiments, the synthetic antibody can provide at least about 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, or 80% survival of the disease in the subject administered the composition. The composition can result in the generation of the synthetic antibody in the subject within at least about 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 20 hours, 25 hours, 30 hours, 35 hours, 40 hours, 45 hours, 50 hours, or 60 hours of administration of the composition to the subject. The composition can result in generation of the synthetic antibody in the subject within at least about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, or 10 days of administration of the composition to the subject. The composition can result in generation of the synthetic antibody in the subject within about 1 hour to about 6 days, about 1 hour to about 5 days, about 1 hour to about 4 days, about 1 hour to about 3 days, about 1 hour to about 2 days, about 1 hour to about 1 day, about 1 hour to about 72 hours, about 1 hour to about 60 hours, about 1 hour to about 48 hours, about 1 hour to about 36 hours, about 1 hour to about 24 hours, about 1 hour to about 12 hours, or about 1 hour to about 6 hours of administration of the composition to the subject. The composition, when administered to the subject in need thereof, can result in the generation of the synthetic antibody in the subject more quickly than the generation of an endogenous antibody in a subject who is administered an antigen to induce a humoral immune response. The composition can result in the generation of the synthetic antibody at Docket No.206193-0136-00WO least about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, or 10 days before the generation of the endogenous antibody in the subject who was administered an antigen to induce a humoral immune response. The composition of the present invention can have features required of effective compositions such as being safe so that the composition does not cause illness or death; being protective against illness; and providing ease of administration, few side effects, biological stability and low cost per dose. Use in Combination with Antibiotics The present invention also provides a method of treating, protecting against, and / or preventing disease in a subject in need thereof by administering a combination of the synthetic antibody, or nucleic acid molecule encoding the synthetic antibody, and one or more additional thereapeutic agent. In some embodiments, the additional therapeutic agent is an antibiotic agent. The synthetic antibody and an antibiotic agent may be administered using any suitable method such that a combination of the synthetic antibody and antibiotic agent are both present in the subject. In one embodiment, the method may comprise administration of a first composition comprising a synthetic antibody of the invention by any of the methods described in detail above and administration of a second composition comprising an antibiotic agent less than 1, less than 2, less than 3, less than 4, less than 5, less than 6, less than 7, less than 8, less than 9 or less than 10 days following administration of the synthetic antibody. In one embodiment, the method may comprise administration of a first composition comprising a synthetic antibody of the invention by any of the methods described in detail above and administration of a second composition comprising an antibiotic agent more than 1, more than 2, more than 3, more than 4, more than 5, more than 6, more than 7, more than 8, more than 9 or more than 10 days following administration of the synthetic antibody. In one embodiment, the method may comprise administration of a first composition comprising an antibiotic agent and administration of a second composition comprising a synthetic antibody of the invention by any of the methods described in detail above less than 1, less than 2, less than 3, less than 4, less than 5, less than 6, less than 7, less than 8, less than 9 or less than 10 days following administration of the antibiotic agent. In one embodiment, the method may comprise administration of a first composition comprising an antibiotic agent and administration of a second composition comprising a synthetic antibody of the invention Docket No.206193-0136-00WO by any of the methods described in detail above more than 1, more than 2, more than 3, more than 4, more than 5, more than 6, more than 7, more than 8, more than 9 or more than 10 days following administration of the antibiotic agent. In one embodiment, the method may comprise administration of a first composition comprising a synthetic antibody of the invention by any of the methods described in detail above and a second composition comprising an antibiotic agent concurrently. In one embodiment, the method may comprise administration of a first composition comprising a synthetic antibody of the invention by any of the methods described in detail above and a second composition comprising an antibiotic agent concurrently. In one embodiment, the method may comprise administration of a single composition comprising a synthetic antibody of the invention and an antibiotic agent. Non-limiting examples of antibiotics that can be used in combination with the synthetic antibody of the invention include aminoglycosides (e.g., gentamicin, amikacin, tobramycin), quinolones (e.g., ciprofloxacin, levofloxacin), cephalosporins (e.g., ceftazidime, cefepime, cefoperazone, cefpirome, ceftobiprole), antipseudomonal penicillins: carboxypenicillins (e.g., carbenicillin and ticarcillin) and ureidopenicillins (e.g., mezlocillin, azlocillin, and piperacillin), carbapenems (e.g., meropenem, imipenem, doripenem), polymyxins (e.g., polymyxin B and colistin) and monobactams (e.g., aztreonam). The present invention has multiple aspects, illustrated by the following non- limiting examples. Examples The present invention is further illustrated in the following Examples. It should be understood that these Examples, while indicating preferred embodiments of the invention, are given by way of illustration only. From the above discussion and these Examples, one skilled in the art can ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions. Thus, various modifications of the invention in addition to those shown and described herein will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims. Example 1: DELIVERY OF AN FC-MODIFIED DNA-ENCODED MONOCLONAL ANTIBODY TARGETING THE PNEUMOCOCCAL HISTIDINE Docket No.206193-0136-00WO TRIAD PROTEIN D (PHTD) IMPROVES PROTECTION DURING FATAL PNEUMOCOCCAL INFECTION VIA ENGAGEMENT WITH COMPLEMENT PROTEINS Streptococcus pneumoniae (pneumococcus, Spn) infection remains a leading cause of death globally despite widespread use of current capsular polysaccharide vaccines. Despite a reduction of pneumococcal disease, these vaccines are limited by serotype specificity with disease persisting for some vaccine serotypes due to immune system evasion capability (i.e., capsule shedding, electronegative cell surface). Therefore, there is a growing need for serotype-inclusive approaches to combat Spn infection. Conserved target antibody- based approaches may bypass serotype limitations and protect against non-vaccine serotypes. A candidate human monoclonal antibody was previous characterized against the conserved surface antigen, pneumococcal histidine triad protein D (PhtD), and demonstrated protective efficacy in fatal Spn challenge. While recombinant antibody therapies are constrained by cold storage and high dose requirements, DNA-delivered monoclonal antibodies (DMAbs) are being developed, produced by muscle cells, for long-term systemic circulation of fully functional Abs by a single injection. Furthermore, pneumococcal vaccines are reported to be protective via opsonophagocytosis, which likely involves complement. To build on this prior work, DMAb variants were developed for direct in vivo expression to drive improved antibody durability, and secondly, an Fc-point mutation was engineered to enhance complement binding activity to improve the in vivo potency of these antibodies compared to DNA-derived mAb without the Fc-complement mutation and recombinant mAb control. Importantly, in vivo expressed anti-PhtD DMAbs retain binding to recombinant antigen and serotype 3 pneumococci. In challenge, positive control protein mAb delivered at the time of challenge was compared to IM delivered WT-Fc DMAb, spanning 200 µg to 25 µg, at day 28-post administration. At the lowest dose of 25 µg, mice showed 50- 58% survival while protection by higher dose groups maxed out at 75% survival which was not statistically significant from recombinant PhtD mAb control. Single point mutations within the Fc-region may improve binding efficacy for effector proteins, like complement, to improve antibody potency and decrease protective dose. Complement enhanced anti-PhtD DMAb (200 µg, 10 µg) was compared to non-complement enhanced DMAb (200 µg, 10 µg) and protein control (as above). Mice administered low dose (10 µg, 30-fold lower) of the complement enhanced anti-PhtD DMAb exhibit similar protection to mice administered high dose WT-Fc DMAb or recombinant PhtD mAb control in fatal Spn 3 intranasal challenge. Docket No.206193-0136-00WO Furthermore, mice administered anti-PhtD DMAbs show persistent expression at protective levels suggesting the application of our DMAbs as a single dose injection for protection lasting over one year. Overall, these studies support previous work on enhanced complement- mediated membrane attack complex (MAC) anti-N. gonorrhea DMAbs (Parzych et. al., Bacteriology 2021) and show further application of Fc-engineering to enhance complement mediated phagocytosis by anti-S. pneumoniae DMAbs at the lung mucosa in a fatal male murine challenge model. The data show that germline reversions in non-essential framework regions improved antibody durability in vivo compared to the fully mature PhtD3 mAb expressed on the DNA plasmid platform. Furthermore, the data shows that a high dose (200 µg) of the GR PhtD3 DMAb protects comparably to a 300 µg dose of recombinant PhtD3 mAb (IP injection) during lethal WU2 intranasal challenge. A complement enhanced version of the PhtD3 DMAb was also generated by the addition of a single point mutation (E430G) to the Fc-region. Here, the data shows that E430G can improve antibody potency and exhibits similar protection to mice administered high dose of WT-Fc DMAb or recombinant PhtD3 mAb control during WU2 challenge. Overall, these studies support previous work on enhanced complement-mediated membrane attack complex (MAC) anti-N. gonorrhea DMAbs (Parzych et. al., 2021) and show further application of Fc-engineering to enhance complement mediated phagocytosis by anti-S. pneumoniae DMAbs at the lung mucosa in a pneumococcal pneumonia challenge model. Figure 1 shows the design and expression of monoclonal antibody PhtD3. Figure 2 shows the design and results of a challenge study. In vivo expression of PhtD3 (GR) DMAb by dose over time post-single administration (n=3) is shown in Figure 2C. Figure 2D shows the percent weight change for all groups during the duration of WU2 challenge. Figure 2D shows the prophylactic efficacy of PhtD3 DMAb doses compared to recombinant PhtD3 mAb. Figure 3 shows the design of complement enhanced PhtD3 DMAb variant using the increased durability germline reverted (GR) dual plasmid system by the addition of an E430G point mutation in the heavy chain (HC). In vitro produced PhtD3 DMAbs bind to full length protein, epitope region AA 1-343, and WU2 pneumococcus compared to recombinant PhtD3 mAb and Isotype IgG control (Figure 3C). Docket No.206193-0136-00WO Figure 4 shows the PhtD3 DMAb variant dose outline for WU2 intranasal challenge. Figure 4C shows the percent weight change for all groups during the duration of WU2 challenge. Figure 4D shows the prophylactic efficacy of PhtD3 DMAb doses compared to recombinant PhtD3 mAb (300 µg per mouse). Figure 4E shows lung WU2 titers 3-days post infection of all treatment groups in comparison to naïve mice. Figure 4F shows blood WU2 titers 3-days post infection of all treatment groups in comparison to naïve mice (one- way ANOVA, pvalue <0.05). Sequences: Sequence identifier Sequence type Sequence description 1 AA PhtD3_HC_Wild Type 2 NA PhtD3_HC_Wild Type (CDS) 3 AA PhtD3_HC_Germline Reverted 4 NA PhtD3_HC_Germline Reverted (CDS) 5 AA PhtD3_LC(k)_Wild Type 6 NA PhtD3_LC(k)_Wild Type (CDS) 7 AA PhtD3_LC(k)_Germline Reverted 8 NA PhtD3_LC(k)_Germline Reverted (CDS) 9 AA PhtD3_HC_MOD1 E430G 10 NA PhtD3_HC_MOD1 E430G (CDS) 11 NA PhtD3_HC_Wild Type (plasmid) 12 NA PhtD3_HC_Germline Reverted (plasmid) 13 NA PhtD3_LC(k)_Wild Type (plasmid) 14 NA PhtD3_LC(k)_Germline Reverted (Plasmid) 15 NA PhtD3_HC_MOD1 E430G (plasmid) SEQ ID NO:1 (AA) PhtD3_HC_Wild Type; MDWTWRILFLVAAATGTHAQVQLVQSGPDVKKPGSSVKVSCKASGAAFESFAFAWVRQA PGQGFEWMGRIIPILETRDYAEKFQGRMTMTTDESTATAYMELNSLRFEDTAVYFCARDGH IMRTTLSDAALDVWGQGTTVIVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT Docket No.206193-0136-00WO VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVE PKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK** SEQ ID NO:2 (nuc) PhtD3_HC_Wild Type; ATGGACTGGACCTGGAGAATCCTGTTCCTGGTGGCAGCAGCAACCGGAACACACGC ACAGGTGCAGCTGGTGCAGAGCGGACCCGATGTGAAGAAGCCTGGCAGCTCCGTGA AGGTGAGCTGCAAGGCATCCGGAGCAGCCTTCGAGTCCTTCGCCTTTGCCTGGGTGA GACAGGCACCAGGACAGGGATTTGAGTGGATGGGCCGGATCATCCCTATCCTGGAG ACCCGCGACTACGCCGAGAAGTTCCAGGGCAGGATGACAATGACCACAGATGAGTC CACCGCCACAGCCTACATGGAGCTGAACTCTCTGAGATTCGAGGACACCGCCGTGTA TTTTTGCGCCAGGGATGGCCACATCATGAGAACCACACTGAGCGACGCCGCCCTGGA CGTGTGGGGACAGGGCACCACAGTGATCGTGTCTAGCGCCTCTACCAAGGGACCAA GCGTGTTTCCACTGGCACCCTCCTCTAAGTCCACCTCTGGCGGCACAGCCGCCCTGG GCTGTCTGGTGAAGGACTATTTCCCAGAGCCCGTGACAGTGTCTTGGAACAGCGGCG CCCTGACCTCTGGAGTGCACACATTTCCAGCCGTGCTGCAGAGCTCCGGACTGTACT CCCTGTCTAGCGTGGTGACCGTGCCTTCCTCTAGCCTGGGCACCCAGACATATATCTG CAACGTGAATCACAAGCCTTCTAATACAAAGGTGGACAAGCGGGTGGAGCCAAAGA GCTGTGATAAGACCCACACATGCCCTCCCTGTCCTGCACCAGAGCTGCTGGGCGGCC CAAGCGTGTTCCTGTTTCCACCCAAGCCCAAGGACACCCTGATGATCTCCCGCACCC CTGAGGTGACATGCGTGGTGGTGGACGTGTCTCACGAGGACCCCGAGGTGAAGTTC AACTGGTACGTGGATGGCGTGGAGGTGCACAATGCCAAGACCAAGCCAAGGGAGGA GCAGTACAATTCCACCTATAGAGTGGTGTCTGTGCTGACAGTGCTGCACCAGGATTG GCTGAACGGCAAGGAGTATAAGTGCAAGGTGAGCAATAAGGCCCTGCCCGCCCCTA TCGAGAAGACCATCTCCAAGGCAAAGGGACAGCCTCGGGAGCCACAGGTGTACACA CTGCCTCCAAGCCGCGAGGAGATGACCAAGAACCAGGTGTCCCTGACATGTCTGGTG AAGGGCTTCTATCCATCTGACATCGCCGTGGAGTGGGAGAGCAATGGCCAGCCCGA GAACAATTACAAGACCACACCCCCTGTGCTGGACTCCGATGGCTCTTTCTTTCTGTAT AGCAAGCTGACCGTGGATAAGTCCAGGTGGCAGCAGGGCAACGTGTTTAGCTGTTCC GTGATGCACGAGGCCCTGCACAATCACTACACACAGAAGTCTCTGAGCCTGTCCCCT GGCAAGTGATAA SEQ ID NO:3 (AA) PhtD3_HC_Germline Reverted; MDWTWRILFLVAAATGTHAQVQLVQSGAEVKKPGSSVKVSCKASGAAFESFAFAWVRQA PGQGLEWMGRIIPILETRDYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYFCARDGHI MRTTLSDAALDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVE PKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK** SEQ ID NO:4 (nuc) PhtD3_HC_Germline Reverted; ATGGACTGGACCTGGAGAATCCTGTTCCTGGTGGCAGCAGCAACCGGAACACACGC ACAGGTGCAGCTGGTGCAGAGCGGAGCAGAGGTGAAGAAGCCAGGCAGCTCCGTG AAGGTGTCCTGCAAGGCCTCTGGCGCCGCCTTTGAGTCCTTCGCCTTTGCCTGGGTG AGACAGGCACCTGGACAGGGACTGGAGTGGATGGGAAGGATCATCCCAATCCTGGA Docket No.206193-0136-00WO GACCCGCGACTACGCCCAGAAGTTCCAGGGCAGGGTGACCATCACAGCCGATGAGA GCACCTCCACAGCCTACATGGAGCTGTCTAGCCTGAGAAGCGAGGACACAGCCGTG TATTTTTGCGCCAGGGATGGCCACATCATGAGAACCACACTGTCCGACGCCGCCCTG ATCGAGAAGACCATCAGCAAGGCAAAGGGACAGCCTCGGGAGCCACAGGTGTACAC ACTGCCTCCATCTCGCGAGGAGATGACCAAGAACCAGGTGAGCCTGACATGTCTGGT GAAGGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGTCCAATGGCCAGCCTG AGAACAATTACAAGACCACACCCCCTGTGCTGGACTCTGATGGCAGCTTCTTTCTGTA TTCCAAGCTGACCGTGGATAAGTCTAGGTGGCAGCAGGGCAACGTGTTTTCCTGTTCT GTGATGCACGAGGCCCTGCACAATCACTACACACAGAAGAGCCTGTCCCTGTCTCCT GGCAAGTGATAA SEQ ID NO:5 (AA) PhtD3_LC(k)_Wild Type; MVLQTQVFISLLLWISGAYGDIVMTQSPVTLSLSPGERATLSCRASQSLTDNYLAWYQQKP GQAPRLLIYAASTRATGIPDRISGSGSGTDFTLTISRVEPEDFAMFYCQQYQNSPFTFGGGT TVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESV TEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC** SEQ ID NO:6 (nuc) PhtD3_LC(k)_Wild Type; ATGGTGCTGCAGACCCAGGTGTTCATCTCCCTGCTGCTGTGGATCTCTGGCGCCTAC GGCGACATCGTGATGACCCAGTCTCCTGTGACACTGTCCCTGTCTCCAGGAGAGAGG GCCACCCTGAGCTGCAGAGCAAGCCAGTCCCTGACAGATAACTACCTGGCCTGGTAT CAGCAGAAGCCAGGACAGGCCCCCAGGCTGCTGATCTATGCAGCATCCACCCGGGC CACAGGCATCCCTGACAGGATCTCTGGCAGCGGCTCCGGAACCGATTTCACCCTGAC AATCTCCAGGGTGGAGCCCGAGGACTTCGCCATGTTTTACTGCCAGCAGTATCAGAA TTCTCCCTTCACCTTCGGCGGCGGCACCACAGTGGAGATCAAGAGAACAGTGGCCGC CCCAAGCGTGTTCATCTTTCCCCCTTCCGACGAGCAGCTGAAGTCTGGCACAGCCAG CGTGGTGTGCCTGCTGAACAACTTCTACCCCCGGGAGGCCAAGGTGCAGTGGAAGG TGGATAACGCCCTGCAGTCTGGCAATAGCCAGGAGTCCGTGACCGAGCAGGACTCTA AGGATAGCACATATTCCCTGAGCTCCACCCTGACACTGTCCAAGGCCGATTACGAGA AGCACAAGGTGTATGCCTGCGAGGTGACCCACCAGGGCCTGTCTAGCCCCGTGACA AAGAGCTTTAACCGCGGCGAGTGTTGATAA SEQ ID NO:7 (AA) PhtD3_LC(k)_Germline Reverted; MVLQTQVFISLLLWISGAYGEIVLTQSPGTLSLSPGERATLSCRASQSLTDNYLAWYQQKP GQAPRLLIYAASTRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYQNSPFTFGGG KTVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQES VTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC** Docket No.206193-0136-00WO SEQ ID NO:8 (nuc) PhtD3_LC(k)_Germline Reverted; ATGGTGCTGCAGACCCAGGTGTTCATCTCCCTGCTGCTGTGGATCTCTGGCGCCTAC GGCGAGATCGTGCTGACCCAGTCTCCTGGCACACTGTCCCTGTCTCCAGGCGAGAGG GCCACACTGAGCTGCAGAGCCAGCCAGTCCCTGACCGACAACTACCTGGCCTGGTAT MDWTWRILFLVAAATGTHAQVQLVQSGAEVKKPGSSVKVSCKASGAAFESFAFAWVRQA PGQGLEWMGRIIPILETRDYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYFCARDGHI MRTTLSDAALDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVE PKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHGALHNHYTQKSLSLSPGK** SEQ ID NO: 10 (nuc) PhtD3_HC_MOD1 E430G; ATGGACTGGACCTGGAGAATCCTGTTCCTGGTGGCAGCAGCAACCGGAACACACGC ACAGGTGCAGCTGGTGCAGAGCGGAGCAGAGGTGAAGAAGCCAGGCAGCTCCGTG AAGGTGTCCTGCAAGGCCTCTGGCGCCGCCTTTGAGTCCTTCGCCTTTGCCTGGGTG AGACAGGCACCTGGACAGGGACTGGAGTGGATGGGAAGGATCATCCCAATCCTGGA GACCCGCGACTACGCCCAGAAGTTCCAGGGCAGGGTGACCATCACAGCCGATGAGA GCACCTCCACAGCCTACATGGAGCTGTCTAGCCTGAGAAGCGAGGACACAGCCGTG TATTTTTGCGCCAGGGATGGCCACATCATGAGAACCACACTGTCCGACGCCGCCCTG GACGTGTGGGGACAGGGCACCACAGTGACCGTGTCCTCTGCCAGCACAAAGGGACC TTCCGTGTTCCCACTGGCACCCAGCTCCAAGTCTACCAGCGGCGGCACAGCCGCCCT GGGATGTCTGGTGAAGGACTATTTCCCAGAGCCAGTGACCGTGAGCTGGAACTCCGG CGCCCTGACCTCCGGAGTGCACACATTTCCTGCCGTGCTGCAGTCTAGCGGCCTGTA CTCTCTGTCCTCTGTGGTGACCGTGCCAAGCTCCTCTCTGGGCACCCAGACATATATC TGCAACGTGAATCACAAGCCATCCAATACAAAGGTGGACAAGCGGGTGGAGCCCAA GTCTTGTGATAAGACCCACACATGCCCTCCCTGTCCTGCACCAGAGCTGCTGGGCGG CCCAAGCGTGTTCCTGTTTCCACCCAAGCCTAAGGACACCCTGATGATCAGCCGCAC CCCAGAGGTGACATGCGTGGTGGTGGACGTGTCCCACGAGGACCCCGAGGTGAAGT TTAACTGGTACGTGGATGGCGTGGAGGTGCACAATGCCAAGACCAAGCCAAGGGAG GAGCAGTACAACTCTACCTATAGAGTGGTGAGCGTGCTGACAGTGCTGCACCAGGAT TGGCTGAACGGCAAGGAGTATAAGTGCAAGGTGTCTAATAAGGCCCTGCCCGCCCCT ATCGAGAAGACCATCAGCAAGGCAAAGGGACAGCCTCGGGAGCCACAGGTGTACAC ACTGCCTCCATCTCGCGAGGAGATGACCAAGAACCAGGTGAGCCTGACATGTCTGGT GAAGGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGTCCAATGGCCAGCCTG AGAACAATTACAAGACCACACCCCCTGTGCTGGACTCTGATGGCAGCTTCTTTCTGTA TTCCAAGCTGACCGTGGATAAGTCTAGGTGGCAGCAGGGCAACGTGTTTTCCTGTTCT GTGATGCACGGCGCCCTGCACAATCACTACACACAGAAGAGCCTGTCCCTGTCTCCT GGCAAGTGATAA Docket No.206193-0136-00WO SEQ ID NO:11 (nuc) PhtD3_HC_Wild Type; GCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTATT AATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACAT AACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTC AATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGG TGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGT ACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACA TGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCA TGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGG ATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAAC GGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCG TGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTAGAGAACCCACTGCTT ACTGGCTTATCGAAATTAATACGACTCACTATAGGGAGACCCAAGCTGGCTAGCGTTTA AACTTAAGCTTGGTACCGAGCTCGGATCCGCCGCCACCATGGACTGGACCTGGAGAA TCCTGTTCCTGGTGGCAGCAGCAACCGGAACACACGCACAGGTGCAGCTGGTGCAG AGCGGACCCGATGTGAAGAAGCCTGGCAGCTCCGTGAAGGTGAGCTGCAAGGCATC CGGAGCAGCCTTCGAGTCCTTCGCCTTTGCCTGGGTGAGACAGGCACCAGGACAGG GATTTGAGTGGATGGGCCGGATCATCCCTATCCTGGAGACCCGCGACTACGCCGAGA AGTTCCAGGGCAGGATGACAATGACCACAGATGAGTCCACCGCCACAGCCTACATG GAGCTGAACTCTCTGAGATTCGAGGACACCGCCGTGTATTTTTGCGCCAGGGATGGC CACATCATGAGAACCACACTGAGCGACGCCGCCCTGGACGTGTGGGGACAGGGCAC CACAGTGATCGTGTCTAGCGCCTCTACCAAGGGACCAAGCGTGTTTCCACTGGCACC CTCCTCTAAGTCCACCTCTGGCGGCACAGCCGCCCTGGGCTGTCTGGTGAAGGACTA TTTCCCAGAGCCCGTGACAGTGTCTTGGAACAGCGGCGCCCTGACCTCTGGAGTGCA CACATTTCCAGCCGTGCTGCAGAGCTCCGGACTGTACTCCCTGTCTAGCGTGGTGAC CGTGCCTTCCTCTAGCCTGGGCACCCAGACATATATCTGCAACGTGAATCACAAGCC TTCTAATACAAAGGTGGACAAGCGGGTGGAGCCAAAGAGCTGTGATAAGACCCACA CATGCCCTCCCTGTCCTGCACCAGAGCTGCTGGGCGGCCCAAGCGTGTTCCTGTTTC CACCCAAGCCCAAGGACACCCTGATGATCTCCCGCACCCCTGAGGTGACATGCGTG GTGGTGGACGTGTCTCACGAGGACCCCGAGGTGAAGTTCAACTGGTACGTGGATGG CGTGGAGGTGCACAATGCCAAGACCAAGCCAAGGGAGGAGCAGTACAATTCCACCT ATAGAGTGGTGTCTGTGCTGACAGTGCTGCACCAGGATTGGCTGAACGGCAAGGAGT ATAAGTGCAAGGTGAGCAATAAGGCCCTGCCCGCCCCTATCGAGAAGACCATCTCCA AGGCAAAGGGACAGCCTCGGGAGCCACAGGTGTACACACTGCCTCCAAGCCGCGAG GAGATGACCAAGAACCAGGTGTCCCTGACATGTCTGGTGAAGGGCTTCTATCCATCT GACATCGCCGTGGAGTGGGAGAGCAATGGCCAGCCCGAGAACAATTACAAGACCAC ACCCCCTGTGCTGGACTCCGATGGCTCTTTCTTTCTGTATAGCAAGCTGACCGTGGAT AAGTCCAGGTGGCAGCAGGGCAACGTGTTTAGCTGTTCCGTGATGCACGAGGCCCTG CACAATCACTACACACAGAAGTCTCTGAGCCTGTCCCCTGGCAAGTGATAACTCGAG TCTAGAGGGCCCGTTTAAACCCGCTGATCAGCCTCGACTGTGCCTTCTAGTTGCCAGC CATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATT CTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAG GCATGCTGGGGATGCGGTGGGCTCTATGGCTTCTACTGGGCGGTTTTATGGACAGCAA GCGAACCGGAATTGCCAGCTGGGGCGCCCTCTGGTAAGGTTGGGAAGCCCTGCAAAG TAAACTGGATGGCTTTCTTGCCGCCAAGGATCTGATGGCGCAGGGGATCAAGCTCTGA TCAAGAGACAGGATGAGGATCGTTTCGCATGATTGAACAAGATGGATTGCACGCAGGT TCTCCGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAACAGACAATCG GCTGCTCTGATGCCGCCGTGTTCCGGCTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGT CAAGACCGACCTGTCCGGTGCCCTGAATGAACTGCAAGACGAGGCAGCGCGGCTATC GTGGCTGGCCACGACGGGCGTTCCTTGCGCAGCTGTGCTCGACGTTGTCACTGAAGC GGGAAGGGACTGGCTGCTATTGGGCGAAGTGCCGGGGCAGGATCTCCTGTCATCTCA CCTTGCTCCTGCCGAGAAAGTATCCATCATGGCTGATGCAATGCGGCGGCTGCATACG Docket No.206193-0136-00WO CTTGATCCGGCTACCTGCCCATTCGACCACCAAGCGAAACATCGCATCGAGCGAGCAC GTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACGAAGAGCATCAGGG GCTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGAGCATGCCCGACGGCGAGGA TCTCGTCGTGACCCATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCCGC TTTTCTGGATTCATCGACTGTGGCCGGCTGGGTGTGGCGGACCGCTATCAGGACATAG CGTTGGCTACCCGTGATATTGCTGAAGAGCTTGGCGGCGAATGGGCTGACCGCTTCCT CGTGCTTTACGGTATCGCCGCTCCCGATTCGCAGCGCATCGCCTTCTATCGCCTTCTTG ACGAGTTCTTCTGAATTATTAACGCTTACAATTTCCTGATGCGGTATTTTCTCCTTACGC ATCTGTGCGGTATTTCACACCGCATCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAA CCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACC CTGATAAATGCTTCAATAATAGCACGTGCTAAAACTTCATTTTTAATTTAAAAGGATCTAG GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCAC TGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCG CGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGG ATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCA AATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACC GCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGT CGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGG GCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAAC TGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGC GGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTC CAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGA GCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAAC GCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTT SEQ ID NO:12 (nuc) PhtD3_HC_Germline Reverted; GCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTATT AATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACAT AACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTC Docket No.206193-0136-00WO ATCCAATACAAAGGTGGACAAGCGGGTGGAGCCCAAGTCTTGTGATAAGACCCACAC ATGCCCTCCCTGTCCTGCACCAGAGCTGCTGGGCGGCCCAAGCGTGTTCCTGTTTCC ACCCAAGCCTAAGGACACCCTGATGATCAGCCGCACCCCAGAGGTGACATGCGTGG Docket No.206193-0136-00WO SEQ ID NO:13 (nuc) PhtD3_LC(k)_Wild Type; GCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTATT AATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACAT AACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTC AATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGG TGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGT ACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACA TGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCA TGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGG ATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAAC GGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCG TGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTAGAGAACCCACTGCTT ACTGGCTTATCGAAATTAATACGACTCACTATAGGGAGACCCAAGCTGGCTAGCGTTTA AACTTAAGCTTGGTACCGAGCTCGGATCCGCCGCCACCATGGTGCTGCAGACCCAGG TGTTCATCTCCCTGCTGCTGTGGATCTCTGGCGCCTACGGCGACATCGTGATGACCCA GTCTCCTGTGACACTGTCCCTGTCTCCAGGAGAGAGGGCCACCCTGAGCTGCAGAGC AAGCCAGTCCCTGACAGATAACTACCTGGCCTGGTATCAGCAGAAGCCAGGACAGG CCCCCAGGCTGCTGATCTATGCAGCATCCACCCGGGCCACAGGCATCCCTGACAGG ATCTCTGGCAGCGGCTCCGGAACCGATTTCACCCTGACAATCTCCAGGGTGGAGCCC GAGGACTTCGCCATGTTTTACTGCCAGCAGTATCAGAATTCTCCCTTCACCTTCGGCG GCGGCACCACAGTGGAGATCAAGAGAACAGTGGCCGCCCCAAGCGTGTTCATCTTTC CCCCTTCCGACGAGCAGCTGAAGTCTGGCACAGCCAGCGTGGTGTGCCTGCTGAACA ACTTCTACCCCCGGGAGGCCAAGGTGCAGTGGAAGGTGGATAACGCCCTGCAGTCT GGCAATAGCCAGGAGTCCGTGACCGAGCAGGACTCTAAGGATAGCACATATTCCCTG AGCTCCACCCTGACACTGTCCAAGGCCGATTACGAGAAGCACAAGGTGTATGCCTGC GAGGTGACCCACCAGGGCCTGTCTAGCCCCGTGACAAAGAGCTTTAACCGCGGCGA GTGTTGATAACTCGAGTCTAGAGGGCCCGTTTAAACCCGCTGATCAGCCTCGACTGTG CCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGA AGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGA GTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATT GGGAAGACAATAGCAGGCATGCTGGGGATGCGGTGGGCTCTATGGCTTCTACTGGGC GGTTTTATGGACAGCAAGCGAACCGGAATTGCCAGCTGGGGCGCCCTCTGGTAAGGTT GGGAAGCCCTGCAAAGTAAACTGGATGGCTTTCTTGCCGCCAAGGATCTGATGGCGCA GGGGATCAAGCTCTGATCAAGAGACAGGATGAGGATCGTTTCGCATGATTGAACAAGA TGGATTGCACGCAGGTTCTCCGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGG GCACAACAGACAATCGGCTGCTCTGATGCCGCCGTGTTCCGGCTGTCAGCGCAGGGG CGCCCGGTTCTTTTTGTCAAGACCGACCTGTCCGGTGCCCTGAATGAACTGCAAGACG AGGCAGCGCGGCTATCGTGGCTGGCCACGACGGGCGTTCCTTGCGCAGCTGTGCTCG ACGTTGTCACTGAAGCGGGAAGGGACTGGCTGCTATTGGGCGAAGTGCCGGGGCAGG ATCTCCTGTCATCTCACCTTGCTCCTGCCGAGAAAGTATCCATCATGGCTGATGCAATG CGGCGGCTGCATACGCTTGATCCGGCTACCTGCCCATTCGACCACCAAGCGAAACATC GCATCGAGCGAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGA CGAAGAGCATCAGGGGCTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGAGCAT GCCCGACGGCGAGGATCTCGTCGTGACCCATGGCGATGCCTGCTTGCCGAATATCATG GTGGAAAATGGCCGCTTTTCTGGATTCATCGACTGTGGCCGGCTGGGTGTGGCGGACC GCTATCAGGACATAGCGTTGGCTACCCGTGATATTGCTGAAGAGCTTGGCGGCGAATG GGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCTCCCGATTCGCAGCGCATCGCC TTCTATCGCCTTCTTGACGAGTTCTTCTGAATTATTAACGCTTACAATTTCCTGATGCGG TATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATCAGGTGGCACTTTTCGGG GAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGC TCATGAGACAATAACCCTGATAAATGCTTCAATAATAGCACGTGCTAAAACTTCATTTTT AATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAAC GTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGA GATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGC Docket No.206193-0136-00WO GGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCA GCAGAGCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTC AAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGC TGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGAT AAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCG AACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTT CCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGA GCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTT CGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTAT GGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCT CACATGTTCTT SEQ ID NO:14 (nuc) PhtD3_LC(k)_Germline Reverted; GCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTATT AATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACAT Docket No.206193-0136-00WO GCATCGAGCGAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGA CGAAGAGCATCAGGGGCTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGAGCAT GCCCGACGGCGAGGATCTCGTCGTGACCCATGGCGATGCCTGCTTGCCGAATATCATG GCTGCTTCGCGATGTACGGGCCAGATATACGCGTTGACATTGATTATTGACTAGTTATT AATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACAT AACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTC AATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGG TGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGT ACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACA TGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCA TGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGG ATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAAC GGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCG TGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTAGAGAACCCACTGCTT ACTGGCTTATCGAAATTAATACGACTCACTATAGGGAGACCCAAGCTGGCTAGCGTTTA AACTTAAGCTTGGTACCGAGCTCGGATCCGCCGCCACCATGGACTGGACCTGGAGAA TCCTGTTCCTGGTGGCAGCAGCAACCGGAACACACGCACAGGTGCAGCTGGTGCAG AGCGGAGCAGAGGTGAAGAAGCCAGGCAGCTCCGTGAAGGTGTCCTGCAAGGCCTC TGGCGCCGCCTTTGAGTCCTTCGCCTTTGCCTGGGTGAGACAGGCACCTGGACAGGG ACTGGAGTGGATGGGAAGGATCATCCCAATCCTGGAGACCCGCGACTACGCCCAGA AGTTCCAGGGCAGGGTGACCATCACAGCCGATGAGAGCACCTCCACAGCCTACATG GAGCTGTCTAGCCTGAGAAGCGAGGACACAGCCGTGTATTTTTGCGCCAGGGATGGC CACATCATGAGAACCACACTGTCCGACGCCGCCCTGGACGTGTGGGGACAGGGCAC CACAGTGACCGTGTCCTCTGCCAGCACAAAGGGACCTTCCGTGTTCCCACTGGCACC CAGCTCCAAGTCTACCAGCGGCGGCACAGCCGCCCTGGGATGTCTGGTGAAGGACT ATTTCCCAGAGCCAGTGACCGTGAGCTGGAACTCCGGCGCCCTGACCTCCGGAGTGC ACACATTTCCTGCCGTGCTGCAGTCTAGCGGCCTGTACTCTCTGTCCTCTGTGGTGAC CGTGCCAAGCTCCTCTCTGGGCACCCAGACATATATCTGCAACGTGAATCACAAGCC ATCCAATACAAAGGTGGACAAGCGGGTGGAGCCCAAGTCTTGTGATAAGACCCACAC ATGCCCTCCCTGTCCTGCACCAGAGCTGCTGGGCGGCCCAAGCGTGTTCCTGTTTCC Docket No.206193-0136-00WO ACCCAAGCCTAAGGACACCCTGATGATCAGCCGCACCCCAGAGGTGACATGCGTGG TGGTGGACGTGTCCCACGAGGACCCCGAGGTGAAGTTTAACTGGTACGTGGATGGC GTGGAGGTGCACAATGCCAAGACCAAGCCAAGGGAGGAGCAGTACAACTCTACCTA TAGAGTGGTGAGCGTGCTGACAGTGCTGCACCAGGATTGGCTGAACGGCAAGGAGT ATAAGTGCAAGGTGTCTAATAAGGCCCTGCCCGCCCCTATCGAGAAGACCATCAGCA AGGCAAAGGGACAGCCTCGGGAGCCACAGGTGTACACACTGCCTCCATCTCGCGAG GAGATGACCAAGAACCAGGTGAGCCTGACATGTCTGGTGAAGGGCTTCTATCCCAGC GACATCGCCGTGGAGTGGGAGTCCAATGGCCAGCCTGAGAACAATTACAAGACCAC ACCCCCTGTGCTGGACTCTGATGGCAGCTTCTTTCTGTATTCCAAGCTGACCGTGGAT AAGTCTAGGTGGCAGCAGGGCAACGTGTTTTCCTGTTCTGTGATGCACGGCGCCCTG CACAATCACTACACACAGAAGAGCCTGTCCCTGTCTCCTGGCAAGTGATAACTCGAG TCTAGAGGGCCCGTTTAAACCCGCTGATCAGCCTCGACTGTGCCTTCTAGTTGCCAGC CATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATT CTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAG GCATGCTGGGGATGCGGTGGGCTCTATGGCTTCTACTGGGCGGTTTTATGGACAGCAA GCGAACCGGAATTGCCAGCTGGGGCGCCCTCTGGTAAGGTTGGGAAGCCCTGCAAAG TAAACTGGATGGCTTTCTTGCCGCCAAGGATCTGATGGCGCAGGGGATCAAGCTCTGA TCAAGAGACAGGATGAGGATCGTTTCGCATGATTGAACAAGATGGATTGCACGCAGGT TCTCCGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAACAGACAATCG GCTGCTCTGATGCCGCCGTGTTCCGGCTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGT CAAGACCGACCTGTCCGGTGCCCTGAATGAACTGCAAGACGAGGCAGCGCGGCTATC GTGGCTGGCCACGACGGGCGTTCCTTGCGCAGCTGTGCTCGACGTTGTCACTGAAGC GGGAAGGGACTGGCTGCTATTGGGCGAAGTGCCGGGGCAGGATCTCCTGTCATCTCA CCTTGCTCCTGCCGAGAAAGTATCCATCATGGCTGATGCAATGCGGCGGCTGCATACG CTTGATCCGGCTACCTGCCCATTCGACCACCAAGCGAAACATCGCATCGAGCGAGCAC GTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACGAAGAGCATCAGGG GCTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGAGCATGCCCGACGGCGAGGA TCTCGTCGTGACCCATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCCGC TTTTCTGGATTCATCGACTGTGGCCGGCTGGGTGTGGCGGACCGCTATCAGGACATAG CGTTGGCTACCCGTGATATTGCTGAAGAGCTTGGCGGCGAATGGGCTGACCGCTTCCT CGTGCTTTACGGTATCGCCGCTCCCGATTCGCAGCGCATCGCCTTCTATCGCCTTCTTG ACGAGTTCTTCTGAATTATTAACGCTTACAATTTCCTGATGCGGTATTTTCTCCTTACGC ATCTGTGCGGTATTTCACACCGCATCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAA CCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACC CTGATAAATGCTTCAATAATAGCACGTGCTAAAACTTCATTTTTAATTTAAAAGGATCTAG GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCAC TGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCG CGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGG ATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCA AATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACC GCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGT CGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGG GCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAAC TGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGC GGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTC CAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGA GCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAAC GCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTT Docket No.206193-0136-00WO It is understood that the foregoing detailed description and accompanying examples are merely illustrative and are not to be taken as limitations upon the scope of the invention, which is defined solely by the appended claims and their equivalents. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications, including without limitation those relating to the chemical structures, substituents, derivatives, intermediates, syntheses, compositions, formulations, or methods of use of the invention, may be made without departing from the spirit and scope thereof.

Claims

Docket No.206193-0136-00WO CLAIMS What is claimed is:

1. An anti-PhtD (pneumococcal histidine triad protein D) antibody or fragment thereof.

2. The anti-PhtD antibody, or fragment thereof, of claim 1, comprising a light chain selected from the group consisting of: (a) SEQ ID NO:5 and SEQ ID NO:7; (b) an amino acid sequence at least 90% identical to SEQ ID NO:5 and SEQ ID NO:7; (c) an amino acid sequence at least 70% of the length of SEQ ID NO:5 and SEQ ID NO:7; and (d) an amino acid sequence at least 90% identical to and at least 70% the length of SEQ ID NO:5 and SEQ ID NO:

7.

3. The anti-PhtD antibody, or fragment thereof, of claim 1, comprising a heavy chain selected from the group consisting of: (a) SEQ ID NO:1, SEQ ID NO:3, and SEQ ID NO: 9; (b) an amino acid sequence at least 90% identical to SEQ ID NO:1, SEQ ID NO:3, and SEQ ID NO: 9; (c) an amino acid sequence at least 70% of the length of SEQ ID NO:1, SEQ ID NO:3, and SEQ ID NO: 9; and (d) an amino acid sequence at least 90% identical to and at least 70% the length of SEQ ID NO:1, SEQ ID NO:3, and SEQ ID NO:

9.

4. The anti-PhtD antibody or fragment thereof of any one of claims 1-3, wherein the antibody is selected from the group consisting of a humanized antibody, a chimeric antibody, a fully human antibody, an antibody mimetic.Docket No.206193-0136-00WO 5. A nucleic acid molecule encoding a light chain of the anti-PhtD antibody, or fragment thereof, of claim 1 or 2.

6. The nucleic acid molecule of claim 5, wherein the nucleotide sequence encoding the light chain is selected from the group consisting of: (a) SEQ ID NO:6 and SEQ ID and NO:8; (b) an amino acid sequence at least 90% identical to SEQ ID NO:6 and SEQ ID and NO:8; (c) an amino acid sequence at least 70% of the length of SEQ ID NO:6 and SEQ ID and NO:8; and (d) an amino acid sequence at least 90% identical to and at least 70% the length of SEQ ID NO:6 and SEQ ID and NO:

8.

7. A nucleic acid molecule encoding a heavy chain of the anti-PhtD antibody, or fragment thereof, of claim 1 or 3.

8. The nucleic acid molecule of claim 7, wherein the nucleotide sequence encoding the heavy chain is selected from the group consisting of: (a) SEQ ID NO:2, SEQ ID NO:4, and SEQ ID NO:10; (b) an amino acid sequence at least 90% identical to SEQ ID NO:2, SEQ ID NO:4, and SEQ ID NO:10; (c) an amino acid sequence at least 70% of the length of SEQ ID NO:2, SEQ ID NO:4, and SEQ ID NO:10; and 9. an amino acid sequence at least 90% identical to and at least 70% the length of SEQ ID NO:2, SEQ ID NO:4, and SEQ ID NO:

10.

10. The nucleic acid molecule of any one of claims 5-8, wherein the nucleotide sequence encodes a leader sequence.

11. The nucleic acid molecule of any one of claims 5-9, wherein the nucleic acid molecule comprises an expression vector.Docket No.206193-0136-00WO 12. A combination of nucleic acid molecules encoding an antibody of claim 1-3, comprising a first nucleic acid molecule encoding the light chain amino acid sequence, and a second nucleic acid molecule encoding the heavy chain amino acid sequence, or a fragment thereof.

13. The combination of nucleic acid molecules of claim 11, wherein the wherein the nucleotide sequence encoding the light chain is selected from the group consisting of: SEQ ID NO:6, and SEQ ID NO:8, or a fragment thereof, and wherein the nucleotide sequence encoding the heavy chain is selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:4, and SEQ ID NO:10, or a fragment thereof.

14. The combination of nucleic acid molecules of claim 11, wherein one or more nucleotide sequence encodes a leader sequence.

15. The combination of nucleic acid molecules of claim 11, wherein one or more nucleic acid molecule comprises an expression vector.

16. A composition comprising at least one anti-PhtD antibody or fragment thereof of any one of claims 1-4.

17. A composition comprising at least one nucleic acid molecule of any one of claims 5-10.

18. A composition comprising a combination of nucleic acid molecules of any one of claims 11-14.

19. The composition of claim 17 or claim 18, further comprising a pharmaceutically acceptable excipient.Docket No.206193-0136-00WO 20. A method of preventing or treating a disease in a subject, the method comprising administering to the subject the antibody or antibody fragment of any one of claims 1-4, the nucleic acid molecule of any one of claims 5-10, the combination of nucleic acid molecules of any one of claims 11-14 or a composition of any one of claims 15-19.

21. The method of claim 20, wherein the disease is Streptococcus pneumoniae infection.

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