OIL-BASED ADJUVANTS
Patent Information
- Authority / Receiving Office
- MX · MX
- Patent Type
- Patents
- Current Assignee / Owner
- AGRICULTURAL RESEARCH SERVICE OF THE U S DEPARTMENT OF AGRICULTURE
- Filing Date
- 2016-03-18
- Publication Date
- 2026-05-19
Abstract
Description
OIL BASED ADJUVANTS FIELD OF THE INVENTION The present invention relates generally to novel adjuvant formulations for enhancing the immune response to antigens for use in immunogenic and vaccine compositions. The present invention also relates to methods of preparation and use of the adjuvant, immunogenic and vaccine compositions. BACKGROUND OF THE INVENTION Bacterial, viral, and parasitic infections are widespread in humans and animals. Diseases caused by these infectious agents are often resistant to antimicrobial pharmaceutical therapy, leaving no effective means of treatment. Consequently, a vaccinological approach is being increasingly used to control infectious diseases. A complete infectious pathogen can be adapted for use in a vaccine formulation after chemical inactivation or appropriate genetic manipulation. Alternatively, a protein subunit from the pathogen can be expressed in a recombinant expression system and purified for use in a vaccine formulation. Vaccines can be made more effective by including an appropriate adjuvant in the composition. The term "adjuvant" refers, in general, to any material that increases the humoral or cellular immune response to an antigen. Adjuvants are used for two purposes: they slow the release of antigen from the injection site and they enhance stimulation of the immune system. Traditional vaccines are generally composed of a crude preparation of inactivated or killed or live modified pathogenic microorganisms. The impurities associated with these cultures of pathological microorganisms can act as an adjuvant enhancing the immune response. However, immunity caused by vaccines using homogeneous preparations of pathological microorganisms or purified protein subunits as antigens is often reduced. The addition of certain exogenous materials such as a builder therefore becomes necessary. Also, in some cases, synthetic and subunit vaccines can be expensive to produce. Also, in some cases, the pathogen cannot be grown on a commercial scale and therefore synthetic / subunit vaccines represent the only viable option. The addition of an adjuvant may allow the use of a lower dose of antigen to stimulate a similar immune response, thus reducing vaccine production costs. Thus, the efficacy of some medicinal agents Al acnn / l 7Π7 / Ε / ΥΙΛΙ injection can be significantly increased by combining the agent with an adjuvant. Many factors must be considered in the selection of an adjuvant. An adjuvant should promote a relatively slow rate of release and absorption of the antigen in an effective manner with a minimum of toxic, allergenic, irritant and other undesirable effects to the host. To be desirable, an adjuvant should be non-virucidal, biodegradable, capable of consistently creating a high level of immunity, capable of stimulating cross-protection, compatible with multiple antigens, effective in multiple species, non-toxic, and safe for the host (e.g. , no injection site reactions). Other desirable characteristics of an adjuvant are that it can be microdosed, allows for dosage savings, has excellent storage stability, is dryable, can be made oil-free, can be present as a solid or a liquid, isotonic , it is easy to manufacture and it is cheap to produce. Finally, it is highly desirable that an adjuvant can be configured to induce an immune, humoral, or cellular response, or both, depending on the requirements of the vaccination scenario. However, the number of adjuvants that can meet the above requirements is limited. The choice of an adjuvant depends on the needs of the vaccine, whether these are an increase in the magnitude or function of the antibody response, an increase in the cell-mediated immune response, the induction of mucosal immunity, or a reduction of the antigen dose. A number of adjuvants have been proposed, but none have been shown to be optimally suitable for all vaccines. The first adjuvant reported in the literature was Freund's complete adjuvant (FCA), which contains a water-in-oil emulsion and mycobacterial extracts. Unfortunately, FCA is poorly tolerated and can cause uncontrolled inflammation. Since the discovery of FCA around 80 years ago, attempts have been made to reduce the unwanted side effects of adjuvants. Some other materials that have been used as builders include metal oxides (for example, aluminum hydroxide), alum, inorganic chelates of salts, gelatins, various paraffin-type oils, synthesized resins, alginates, mucoid and polysaccharide compounds, caseinates, and derivative substances. of the blood such as fibrin clots. Although these materials are generally effective in stimulating the immune system, none have been found to be entirely satisfactory due to adverse effects in the host (eg, sterile abscess production, organ damage, carcinogenicity, or allergenic responses) or Undesired pharmaceutical properties (eg rapid dispersion or poor dispersion control from the injection site, or swelling of the material). ri acnn / i znz / E / YiAi BRIEF DESCRIPTION OF THE INVENTION The present invention provides novel vaccine compositions and adjuvant formulations useful for vaccines. In the first aspect, the invention provides an adjuvant formulation comprising an oil phase and an aqueous phase, wherein the oil phase comprises at least 50% of the formulation v / v, said formulation comprising at least one monophosphoryl lipid. A (MPLA) or an analogue thereof and an immunostimulatory oligonucleotide, with the provisos that a) if said immunostimulatory oligonucleotide is absent, then the composition comprises a poly I:C, a glycolipid and, optionally, a quaternary amine; or a polycationic vehicle and b) if said monophosphoryl-lipid A (MPL-A) or the analogue thereof is absent, then the formulation comprises a source of aluminum and, optionally, a polycationic vehicle. In different embodiments, the oil phase may comprise an oil and, optionally, an oil-soluble emulsifier. In some embodiments, both said monophosphoryl-lipid A (MPL-A) and the analogue thereof are present in the adjuvant formulation. In these embodiments, the formulation further comprises a steral (eg, cholesterol), a poly I:C, or a combination thereof. In certain sets of embodiments, in addition to the oil and optional emulsifier(s), adjuvant formulations include a combination of monophosphoryl-lipid A (MPL-A) or an analog thereof, a steral, and an immunostimulatory oligonucleotide (TCMO). The adjuvant formulation can also optionally comprise poly I:C (TCMYO) and / or a saponin (QTCMO or QTCMYO, respectively). In still other alternative embodiments, in addition to the oil and optional emulsifier(s), formulation adjuvants also include a combination of a quaternary amine, glycolipid, MPL-A or analog thereof, and poly I:C (ODYRM). In yet another set of embodiments, in addition to the oil and optional emulsifier(s), the adjuvant formulations also include a combination of a saponin, a ester, a quaternary amine, a polycationic carrier, provided that if said polycationic carrier is DEAE-dextran, then the antigen is not E. coli J-5 bacterin (QCDXO). In other embodiments, in addition to the oil and optional emulsifier(s), the adjuvant may include the immunostimulatory oligonucleotide, a source of aluminum, and optionally a polycationic carrier (TOA and TXO-A, respectively). In a second aspect, the adjuvant formulation according to any of the modalities mentioned above can include an antigenic component, thus forming a Al QCnn / l 7Α7 / Β / ΥΙΛΙ vaccine composition, provided that the antigen is not E Coli J-5 protein if the adjuvant formulation consists of (or consists essentially of) DEAE-dextran, Quil A, cholesterol and DDA, or if the adjuvant formulation consists of (or consists essentially of) DEAEdextran and the immunostimulatory oligonucleotide. In certain embodiments, vaccines of this aspect contain antigen(s) derived from pathogens affecting cattle, sheep, horses, or swine. In other embodiments, vaccines of this aspect contain antigen(s) derived from pathogens affecting poultry or felines. In further aspects of the invention, different combinations of the antigenic compound and adjuvant formulations are provided. More specifically, in the third aspect, the invention provides a vaccine composition comprising an Eimeria maxima and / or Clostridium perfringens antigen and an adjuvant formulation. In different embodiments of this third aspect, the adjuvant formulation may include an oil phase, said oil phase being present in an amount of at least 50% v / v of the composition, a polycationic carrier and, optionally, an immunostimulatory oligonucleotide. In other embodiments of this aspect of the invention, the invention provides a vaccine composition comprising an adjuvant component comprising an oil phase, said oil phase being present in an amount of at least 50% v / v of the composition, an immunostimulatory oligonucleotide, a steral and a monophosphoryl-lipid A (MPL-A) or an analog thereof. In the fourth aspect, the invention provides a vaccine composition comprising a Neospora antigen and an adjuvant formulation. In different embodiments of the invention according to this aspect, the adjuvant formulation comprises an oily phase, said oily phase being present in an amount of at least 50% v / v of the composition, a monophosphoryl-lipid A (MPL-A) or an analogue thereof. In other embodiments, the adjuvant formulation comprises an oil phase, said oil phase being present in an amount of at least 50% v / v of the composition, an immunostimulatory oligonucleotide, and a polycationic carrier. In the fifth aspect, the invention provides a vaccine composition comprising a Chlamydophila abortis antigen and an adjuvant formulation comprising an oily phase, said oily phase being present in an amount of at least 50% v / v of the composition, a steral, an immunostimulatory oligonucleotide, monophosphoryl-lipid A (MPL-A) or an analog thereof, and poly I:C. In the sixth aspect, the invention provides a vaccine composition comprising a Streptococcus uberis (S. uberis) antigen and an adjuvant formulation comprising an oil phase, said oil phase being present in an amount of at least 50 Ei acnn / i ζηζ / Ε / γίΛΐ % v / v of the composition, and a polycationic vehicle. In different embodiments of this sixth aspect of the invention, the adjuvant formulation also includes an immunostimulatory oligonucleotide. Alternatively or additionally, the adjuvant formulations can include a saponin, a sterol and a quaternary amine. In the seventh aspect, the invention provides a vaccine composition comprising myostatin as the antigenic component and an adjuvant formulation, said adjuvant formulation comprising an oil phase, said oil phase being present in an amount of at least 50% v / v of the composition, an immunostimulatory oligonucleotide, and any of: a polycationic carrier, or MPL-A or an analog thereof. In a number of embodiments according to this aspect of the invention, the adjuvant formulation comprises MPL-A or an analogue thereof. In some embodiments of this set, the adjuvant formulation contains less than 0.5 ug of a sterol per 50 ul of said vaccine composition, and preferably does not contain cholesterol. The choice of myostatin depends on the target species. In a selected embodiment, the selected species is chicken and the source of myostatin is chicken myostatin. In the eighth aspect, the invention provides a vaccine composition comprising A. pyogenes (formerly known as Arcanobacterium pyogenes, Actinomyces pyogenes or Corynebacterium pyogenes, now known as Trueperella pyogenes) antigen and an adjuvant formulation, wherein the adjuvant formulation comprises an oily phase, said oily phase being present in an amount of at least 50% v / v of the composition, an immunostimulatory oligonucleotide and a polycationic carrier. In the ninth aspect, the invention provides a vaccine composition comprising an E coH antigen, a BRV antigen or a BCV antigen, and an adjuvant formulation, wherein said adjuvant formulation comprises an oil phase present in an amount of at least 50% v / v of said vaccine composition, an immunostimulatory oligonucleotide and at least one of a polycationic carrier and a source of aluminum. In the tenth aspect, the invention provides a vaccine composition comprising a Rhipicepha / us microp / us antigen and an adjuvant, said adjuvant being selected from the group consisting of: a) an aqueous adjuvant comprising an immunostimulatory oligonucleotide, a saponin , a sterol, a quaternary amine, a polyacrylic polymer and a glycolipid and b) an oil-based adjuvant comprising an oily phase present in an amount of at least 50% v / v of the vaccine composition and comprising an immunostimulatory oligonucleotide and a polycationic vehicle. In the eleventh aspect, the invention provides a vaccine composition comprising an antigen against foot-and-mouth disease virus (FMDV) and an adjuvant formulation, said adjuvant formulation comprising an oil phase present in an amount of at Ei acnn / i znz / E / YiAi minus 50% v / v of said vaccine composition, an immunostimulatory oligonucleotide and a polycationic vehicle. In different embodiments, the FMDV antigen can be either wild-type, genetically modified and / or attenuated FMDV strains of FMDV, or recombinantly expressed FMDV structural proteins such as virus-like particles (VLPs). ) of serotypes A, C, O, Asian, SAT1, SAT2 or SAT3. In the twelfth aspect, the invention provides a method of generating diagnostic or therapeutic antibodies, the method comprising immunizing a source animal with the adjuvant formulation according to any of the modalities according to the first aspect of the invention and antigen, followed by the extracting a source of the antibodies from the source animal and, if necessary, purifying the antibodies. In certain embodiments, the source animal is a rat, mouse, guinea pig, hamster, cattle, goat, rabbit, horse, pig, or sheep. In some other embodiments, the source animal is a cat or a dog. In some embodiments, particularly suitable for polyclonal antibodies, the source of the antibodies is a whey or milk. In embodiments suitable for monoclonal antibodies, the suitable source of antibodies is a spleen cell. In certain embodiments, the adjuvant formulation comprises an immunostimulatory oligonudetic and a polycationic carrier. The builder may optionally contain a source of aluminum, the source of aluminum comprising, which may be an aluminum hydroxide gel. In certain embodiments, the immunostimulatory oligonucleotide is a CpG and the polycationic carrier is DEAE-dextran. In certain embodiments, the antigen can be selected from FeLVgp70, bovine parainfluenza virus-3 BPI-3 (HN protein), Histophüus somni p31, Bordetella FHA, Parapox, BVDV1 gp53, BVDV2 gp53, Clostridia toxins, canine circovirus, Brachyspira hyodysenteriae (pig species); inactivated whole cell and inactivated digestive pepsin. The invention also provides methods of using the vaccines according to the third to twelfth aspects of the present invention. DETAILED DESCRIPTION OF THE INVENTION Around or Approximately, when used in connection with a measurable numerical variable, refers to the indicated value of the variable and all values of the variable that are within experimental error of the indicated value (for example, within 95% of the confidence interval for the mean) or within 10 percent of the indicated value, if this is Rl acnn / l 7Π7 / Ε / ΥΙΛΙ greater, unless approximately is used with reference to time intervals in weeks, in which approximately 3 weeks is 17 to 25 days, and approximately 2 to approximately 4 weeks is 10 to 40 days. Adjuvant means any substance that increases the humoral or cellular immune response to an antigen. Adjuvants are generally used for two purposes: controlled release of antigen from the injection site and stimulation of the immune system. Builder formulation refers to formulations having builder properties. Alkyl refers to both linear and branched saturated hydrocarbon moieties. Amine refers to a chemical compound that contains nitrogen. Amines are a group of compounds derived from ammonia by replacing the hydrogen atoms with hydrocarbon groups. Quaternary amine refers to an ammonium-based compound with four hydrocarbon groups. "Antibody" refers to an immunoglobulin molecule that can bind to a specific antigen as a consequence of an immune response to that antigen. Immunoglobulins are serum proteins composed of light and heavy polypeptide chains that have constant and variable regions and are divided into classes (eg, IgA, IgD, IgE, IgG, and IgM) based on the composition of the constant regions. Antigen or immunogen refers to any substance that is recognized by the animal's immune system and elicits an immune response. The term includes dead, inactivated, attenuated or live modified bacteria, viruses or parasites. The term "antigen" also includes polynucleotides, polypeptides, recombinant proteins, synthetic peptides, protein extract, cells (including tumor cells), tissues, polysaccharides or lipids, or fragments thereof, individually or in any combination thereof. The term "antigen" also includes antibodies, such as anti-diotypic antibodies or fragments thereof, and synthetic peptide mimotopes that can mimic an antigen or antigenic determinant (epitope). Bacterin means a suspension of one or more killed bacteria that can be used as a component of a vaccine or immunogenic composition. pH buffer means a chemical system that prevents a change in the concentration of another chemical substance, eg proton donor and acceptor systems serve as buffers preventing pronounced changes in hydrogen concentration (pH). Another example of a pH buffer solution is a solution that contains a mixture of a weak acid and its salt (conjugate base) or a weak base and its salt (conjugate acid). Cellular immune response or cell-mediated immune response is Rl acnn / l 7Π7 / Ε / ΥΙΛΙ a response mediated by T cells or other leukocytes or both, and includes the production of cytokines, chemokines, and similar molecules produced by activated T cells, activated leukocytes, or both; or a T cell or other immune cell response that kills an infected cell Companion Animals refers to dogs, cats and equines. Consisting essentially, as applied to adjuvant formulations, refers to a formulation that does not contain additional adjuvant or immunomodulatory agents not mentioned in the amounts at which said agent exerts measurable adjuvant or immunomodulatory effects. Delayed-type hypersensitivity (DTH) refers to an inflammatory response that develops 24 to 72 hours after exposure to an antigen that the immune system recognizes as foreign. This type of immune response primarily involves T cells rather than antibodies (which are made from B cells). Dose refers to a vaccine or immunogenic composition administered to a subject. A first dose or boost vaccine refers to the dose of said composition administered on day 0. A second dose or a third dose or an annual dose refers to an amount of said composition administered subsequent to the first dose, which may or may not be the same vaccine or immunogenic composition as the first dose. The term emulsifier is used extensively in the present disclosure. Includes substances generally accepted as emulsifiers, for example different products from the TWEEN® or SPAN® product lines (fatty acid esters of polyethoxylated sorbitol and fatty acid substituted sorbitan surfactants, respectively) and different solubility enhancers such as oil of PEG-40 castor or other PEGylated hydrogenated oils. Humoral immune response refers to a response that is mediated by antibodies. "Immune response in a subject" refers to the development of a humoral immune response, a cellular immune response, or a humoral and cellular immune response to an antigen. Immune responses can usually be determined using standard immunoassays and neutralization assays, which are known in the art. Immunologically protective amount or immunologically effective amount or effective amount to elicit an immune response of an antigen is an amount effective to induce an immunogenic response in the recipient. The immunogenic response may be sufficient for diagnostic or other testing purposes, or may be adequate to prevent signs or symptoms of disease, including adverse health effects or complications thereof, caused by infection with a disease agent. Humoral immunity or cell-mediated immunity or both may be induced. The immunogenic response of an animal to an immunogenic composition Rl ocnn / l 7Π7 / Β / ΥΙΛΙ can be assessed, for example, indirectly by measuring antibody titers, lymphocyte proliferation assays or directly by monitoring signs and symptoms after challenge with a wild-type strain, while the protective immunity conferred by a vaccine can be assessed by measuring, for example, the reduction of clinical signs such as mortality, morbidity, temperature value, general physical condition and general health and behavior of the subject. The immune response may comprise, without limitation, the induction of cellular and / or humoral immunity. Immunogenic means that it elicits an immune or antigenic response. Thus, an immunogenic composition would be any composition that induces an immune response. "Immunostimulatory molecule" refers to a molecule that stimulates an antigen-nonspecific immune response. Lipids refers to any of a group of organic compounds, including fats, oils, waxes, sterols, and triglycerides that are insoluble in water but soluble in nonpolar organic solvents, are oily to the touch, and together with carbohydrates and proteins make up the material main structure of living cells. Pharmaceutically acceptable refers to substances, which are within the scope of medical judgment, suitable for use in contact with the tissues of subjects without toxicity, irritation, undue allergic responses, and the like, proportional to a reasonable benefit versus risk ratio, and efficacious. in its intended use. The term "poly I:C" refers to naturally occurring polymers of polyinosinic:polycytidylic acids, as well as synthetic forms thereof, eg, backbone stabilized and preferably having TLR-3 antagonist activity. Reactogenicity refers to side effects elicited in a subject in response to administration of an adjuvant, immunogenic composition, or vaccine composition. This can take place at the site of administration and is usually assessed in terms of the development of a range of symptoms. These symptoms can include swelling, redness, and abscesses. It is also evaluated in terms of onset, duration, and severity. A low reaction would imply, for example, a swelling that is only detectable by palpation and not with the naked eye, or it would be of short duration. A more serious reaction would be, for example, one that is visible to the naked eye or lasts longer. Room temperature means a temperature of 18 to 25 °C. Saponin refers to a group of surface-active glycosides of plant origin composed of a hydrophilic region (usually several sugar chains) together with a hydrophobic region of either steroid or triterpenoid structure. ri acnn / i znz / R / YiAi Steroids refers to any of a group of organic compounds belonging to the biochemical class of lipids, which are readily soluble in organic solvents and sparingly soluble in water. Steroids comprise a fused four-ring system of three fused cyclohexane (six carbon) rings plus a fourth cyclopentane (five carbon) ring. Sterols refers to compounds present in animals that are biologically produced from terpenoid precursors. They comprise a steroid ring structure having a hydroxyl (OH) group, usually attached to carbon 3. The hydrocarbon chain of the fatty acid substituent varies in length, usually from 16 to 20 carbon atoms, and may be saturated or unsaturated. Sterols typically contain one or more double bonds in the ring structure and also a variety of ring-attached substituents. Sterols and their fatty acid esters are essentially insoluble in water. Subject refers to any animal for which administration of an adjuvant composition is desired. Includes mammals and non-mammals, including primates, livestock, companion animals, laboratory test animals, captive wild animals, birds (including embryos), reptiles, and fish. Thus, this term includes, but is not limited to, monkeys, humans, pigs, cattle, sheep, goats, equines, mice, rats, guinea pigs, hamsters, rabbits, felines, canids, chickens, turkeys, ducks, other poultry. , frogs and lizards. TCID50 refers to cell culture infectious dose and is defined as the dilution of a virus required to infect 50% of a given batch of inoculated cell cultures. Various procedures can be used to calculate TCID50, including the SpearmanKarber procedure, which is used throughout the present specification. For a description of the Spearman-Karber procedure see B.W. Mahy and H.O. Kangro, Virology Methods Manual, p. 25-46 (1996). "Therapeutically effective amount" refers to that amount of an antigen or vaccine that will induce an immune response in a subject receiving the antigen or vaccine that is adequate to prevent or reduce signs or symptoms of disease, including adverse health effects or complications. thereof, caused by infection with a pathogen, such as a virus or a bacterium. Either humoral immunity or cell-mediated immunity or both humoral and cell-mediated immunity can be induced. The immunogenic response of an animal to a vaccine can be assessed, for example, indirectly by measuring antibody titers, lymphocyte proliferation assays, or directly by monitoring signs and symptoms after challenge with a wild-type strain. The protective immunity conferred by a vaccine can be assessed by measuring, for example, the reduction of clinical signs such as mortality, morbidity, temperature value, general physical condition and general health and Rl acnn / l 7Π7 / Β / ΥΙΛΙ behavior of the subject. The amount of a vaccine that is therapeutically effective can vary depending on the particular adjuvant used, the particular antigen used, or the condition of the subject and can be determined by one of skill in the art. Treating refers to preventing a disorder, condition, or disease to which such term applies, or preventing or reducing one or more symptoms of such disorder, condition, or disease. Treatment refers to the act of treating as defined above. Triterpenoids refers to a large and diverse class of naturally occurring organic molecules, derived from six five-carbon isoprene (2-methyl-1,3-butadiene) units, which can be assembled or modified in thousands of ways. Most are multicyclic structures that differ from each other in functional groups and in their basic carbon skeletons. These molecules can be found in all kinds of living things. "Vaccine" refers to a composition that includes an antigen, as defined herein. Administration of the vaccine to a subject results in an immune response, generally against one or more specific diseases. The amount of a vaccine that is therapeutically effective can vary depending on the particular antigen used or the condition of the subject and can be determined by one of skill in the art. Adjuvant formulations and manufacturing processes The present application discloses various adjuvant formulations suitable for the present invention. The common feature of these adjuvants is the presence of oil and one or more emulsifiers, where the oil phase comprises more than 50% of the vaccine composition comprising the adjuvant formulations disclosed herein. Multiple oils and combinations thereof are suitable for use in the present invention. These oils include, without limitation, animal oils, vegetable oils, as well as non-metabolizable oils. Non-limiting examples of suitable vegetable oils in the present invention are corn oil, peanut oil, soybean oil, coconut oil, and olive oil. A non-limiting example of animal oils is squalene. Suitable non-limiting examples of non-metabolizable oils include light mineral oil, straight or branched chain saturated oils and the like. In a number of embodiments, the oil used in the adjuvant formulations of the present invention is a light mineral oil. As used herein, the term "mineral oil" refers to a mixture of liquid hydrocarbons obtained from petrolatum by a distillation technique. The expression is synonymous with liquefied paraffin, liquid petrolatum, and white mineral oil. The term is also intended to include ri acnn / i znz / E / YiAi light mineral oil, ie, oil which is similarly obtained by distillation of petrolatum, but which has a slightly lower specific gravity than white mineral oil. See, for example, Remington's Pharmaceutical Sciences, 18th Edition (Easton, Pa.: Mack Publishing Company, 1990, at pages 788 and 1323). Mineral oil can be obtained from various commercial sources, eg, 1 T. Baker (Phillipsburg, Pa.), USB Corporation (Cleveland, Ohio). A preferred mineral oil is commercially available light mineral oil under the name DRAKEOL®. Normally, the oil phase is present in an amount of 50% to 95% by volume; preferably in an amount of more than 50% to 85%; more preferably in an amount of greater than 50% to 60% and most preferably in an amount of greater than 50-52% v / v of the vaccine composition. The oil phase includes oil and emulsifiers (eg SPAN® 80, TWEEN® 80, etc.), if any such emulsifiers are present. The volume of the oily phase is calculated as the sum of the volumes of the oil and the emulsifier(s). Thus, for example, if the volume of the oil is 40% and the volume of the emulsifier(s) is 12% of a composition, then the oil phase would be present at 52% v / v of the composition. Similarly, if the oil is present at about 45% and the emulsifier(s) are present at about 6% of a composition, then the oil phase is present at about 51% v / v. of the composition. It will also be understood that since the adjuvants of the present invention form only a part of the vaccines of the present invention, the oil phase is present in an amount of 50% to 95% by volume; preferably in an amount of more than 50% to 85%; more preferably in an amount of 50-60% and most preferably in an amount of 50-52% v / v of each of the adjuvants of the present invention. In a subset of embodiments, applicable to all adjuvants / vaccines of the present invention, the volume percentage of oil and oil-soluble emulsifier together is at least 50%, eg 50 to 95% by volume; preferably an amount of more than 50% to 85%; more preferably an amount of greater than 50% to 60% and most preferably an amount of 50-52% v / v of the vaccine composition. Thus, for example and without limitation, the oil may be present in an amount of 45% and the lipid soluble emulsifier would be present in an amount of more than 5% v / v. Thus, the percentage by volume of the oil and the oil-soluble emulsifier together would be at least 50%. In yet another subset, applicable to all the vaccines of the invention, the percentage by volume of the oil is greater than 40%, for example from 40% to 90% by volume; from 40% to 85%; from 43% to 60%, from 44-50% v / v of the vaccine composition. ri acnn / i ζηζ / Ε / γίΛΐ Suitable emulsifiers for use in the present emulsions include natural biologically compatible emulsifiers and unnatural synthetic surfactants. Biologically compatible emulsifiers include phospholipid compounds or a mixture of phospholipids. Preferred phospholipids are phosphatidylcholines (lecithin), such as soy or egg lecithin. Lecithin can be obtained as a mixture of phosphatides and triglycerides by washing crude vegetable oils with water and separating and drying the resulting hydrated gums. A refined product can be obtained by fractionating the mixture into acetone-insoluble phospholipids and glycolipids remaining after removing triglycerides and vegetable oil by washing with acetone. Alternatively, lecithin can be obtained from various commercial sources. Other suitable phospholipids include phosphatidylglycerin, phosphatidylinositol, phosphatidylserine, phosphatidic acid, cardiolipin, and phosphatidylethanolamine. Phospholipids can be isolated from natural sources or synthesized in a conventional manner. In additional embodiments, the emulsifiers used herein do not include lecithin, or use lecithin in an amount that is immunologically ineffective. Non-natural synthetic emulsifiers for use in the builder formulations of the present invention include sorbitan-based nonionic surfactants, for example fatty acid substituted sorbitan surfactants (commercially available under the designation SPAN® or ARLACEL®), fatty acid esters polyethoxylated sorbitol (TWEEN®), polyethylene glycol esters of fatty acids from sources such as castor oil (EMULFOR®); polyethoxylated fatty acid (eg, stearic acid available under the name SIMULSOL® M-53), polyethoxylated isooctylphenol / formaldehyde polymer (TYLOXAPOL®), fatty polyoxyethylene alcohol ethers (BRIJ®); polyoxyethylene-nonphenyl ethers (TRITON® N), polyoxyethyleneisooctylphenyl ethers (TRITON® X). Preferred synthetic surfactants are those surfactants available under the names SPAN® and TWEEN®, such as TWEEN®-80 (polyoxyethylene (20) sorbitan monooleate) and SPAN®-80 (sorbitan monooleate). In general, the emulsifier(s) may be present in the vaccine composition in an amount of 0.01% to 40% by volume, preferably 0.1% to 15%, more preferably 2% to 10%. Additional ingredients present in the present adjuvant formulations include cationic carriers, immunostimulatory oligonucleotides, monophospholipid A and analogues thereof (MPL-A), poly¡nosín¡co:pol¡cytidíl¡co (poly I:C) acid, saponins , quaternary ammoniums, sterols, glycolipids, a source of aluminum (eg, REHYDRAGEL® or VAC 20® wet gel) and combinations thereof. Suitable cationic carriers include, without limitation, dextran, DEAEdextran (and derivatives thereof), PEG, guar gums, citoseno derivatives, Al acnn / l 7Π7 / Ε / ΥΙΛΙ polycellulose such as hydroxyethylcellulose (HEC), polyethyleneimene, polyaminos such as polylysine and the like. Suitable immunostimulatory oligonucleotides include ODN (DNA-based), ORN (RNA-based) oligonucleotides, or ODN-ORN chimeric backbones, which may have modified backbones including, without limitation, phosphorothioate modifications, halogenations, alkylation (e.g., ethyl or methyl) and phosphodiester modifications. In some embodiments, poly-inosinic-cytidylic acid or derivatives thereof (poly I:C) may be used. CpG oligonucleotides are a recently described class of pharmacotherapeutic agents that are characterized by the presence of an unmethylated CG dinucleotide in specific base sequence contexts (CpG motif). (Hansel TT, Barnes PJ (eds): New Drugs for Asthma, Allergy and COPD. Prog Respir Res. Basel, Karger, 2001, vol 31, pages 229-232, which is incorporated herein by reference). These CpG motifs are not seen in eukaryotic DNA, where the CG dinucleotides are deleted and, when present, are usually methylated, but are present in bacterial DNA to which they confer immunostimulatory properties. In selected embodiments, the adjuvants of the present invention use a so-called P-class immunostimulatory oligonucleotide, more preferably modified P-class immunostimulatory oligonucleotides, even more preferably E-modified P-class oligonucleotides. P-class immunostimulatory oligonucleotides are CpG oligonucleotides characterized by the presence of palindromes, generally 6-20 nucleotides in length. P-class oligonucleotides have the ability to spontaneously self-assemble into concatemers, in vitro and / or in vivo. These oligonucleotides are, in a strict sense, single-stranded, but the presence of palindromes allows the formation of concatemers or possibly stem-loop structures. The total length of P-class immunostimulatory oligonucleotides is between 19-100 nucleotides, 19-30 nucleotides, 30-40 nucleotides, 40-50 nucleotides, 50-60 nucleotides, 60-70 nucleotides, 70-80 nucleotides, 80-90 nucleotides, 90-100 nucleotides. In one aspect of the invention the immunostimulatory oligonucleotide contains a 5' TLR activation domain and at least two palindromic regions, a palindromic region being a 5' palindromic region of at least 6 nucleotides in length and connected to a 3' palindromic region. at least 8 nucleotides in length, directly or through a spacer. P-class immunostimulatory oligonucleotides can be modified according to techniques known in the art. For example, the J modification refers to iodinated nucleotides. Modification E refers to ethyl modified nucleotide(s). Thus, the Al QCnn / l 7Α7 / Β / ΥΙΛΙ E-modified P-class immunostimulatory oligonucleotides are immunostimulatory oligonucleotides in which at least one nucleotide (preferably the 5' nucleotide) is ethylated. Additional modifications include 6-nitro-benzimidazole linkage, O-methylation, proynyl-dU modification, inosine modification, 2-bromovinyl linkage (preferably to uridine). P-class immunostimulatory oligonucleotides may also contain a modified internucleotide linkage including, without limitation, phosphodiester linkages and phosphorothioate linkages. The oligonucleotides of the present invention can be synthesized or obtained from commercial sources. P-class oligonucleotides and modified P-class oligonucleotides are also disclosed in published PCT application WO2008 / 068638, published June 12, 2008. Suitable non-limiting examples of modified P-class immunostimulatory oligonucleotides are provided below (In the following SEQ ID NO:1-10, *refers to a phosphorothioate bond and refers to a phosphodiester bond). In SEQ ID NOs: 11-14, all the linkages are phosphodiester linkages. SEQ ID N°: 1: 5' T*C_G*T*C_G*A*C_G*A*T*C_G*G*C*G*C_G*C*G*C*C*G 3' SEQ ID NO: 2: 5' T*C_G*A*C*G*T*C*G*A*T*C*G*G*C*G*C*G*C*G*C*C *G3' SEQ ID N°: 3 : 5' T*C*G*A*C*G*T*C*G*A*T*C*G*G*C*G*C*G*C*G*C *C*G*T 3' SEQ ID N°: 4 : 5' JU*C_G*A*C*G*T*C*G*A*T*C*G*G*C*G*C*G*C*G*C*C *G3' SEQ ID NO: 5: 5' JU*C_G*A*C*G*T*C*G*A*T*C*G*G*C*G*C*G*C*G*C*C * G*T 3' SEQ ID NO: 6: 5' JU*C*G*A*C*G*T*C*G*A*T*C*G*G*C*G*C*G *C*G*C*C* G*T 3' SEQ ID No: 7: 5' EU*C_G*A*C*G*T*C*G*A*T*C*G*G*C *G*C*G*C*G*C*C*G 3' SEQ ID NO: 8: 5' JU*C_G*T*C*G*A*C*G*A*T*C*G *G*C*G*G*C*C*G*C*C* G*T 3' SEQ ID NO: 9: 5' JU*C*G*T*C*G*A*C*G *A*T*C*G*G*C*G*G*C*C*G*C*C* G*T 3' SEQ ID NO: 10: 5' T*C_G*T*C_G*A *C_G*A*T*C_G*G*C*G*C_G*C*G*C*C*G 3' SEQ ID NO: 11: 5'-UUGUUGUUGUUGUUGUUGUUU-3' SEQ ID NO: 12: 5 '-UUAUUAUUAUUAUUAUUAUU-3' SEQ ID NO: 13: 5'-AAACGCUCAGCCAAAGCAG-3' SEQ ID NO: 14: 5'-dTdCdGdTdCdGdTdTdTdTrGrUrUrGrUrGrUdTdTdTdT-3' The amount of P-class immunostimulatory oligonucleotides for use in the adjuvant compositions depends on the nature of the P-class immunostimulatory oligonucleotide used and the species in question. Suitable MPL-A analogs include, without limitation, may be structurally or unchanged, structurally altered or synthetic, bacterial-derived natural LPS, glucopyranosyl-lipid (GLA) adjuvant, pertactin, various substitutions at the 3-0 sugar position reductive, ri acnn / i znz / E / YiAi synthetic forms of lipid A analogues with low endotoxicity. Sterols share a common chemical nucleus, which is a steroid ring structure[s] having a hydroxyl (OH) group, usually attached to carbon 3. The hydrocarbon chain of the fatty acid substituent varies in length, usually 16 to 20 carbon atoms, and can be saturated or unsaturated. Sterols typically contain one or more double bonds in the ring structure and also a variety of ring-attached substituents. Sterols and their fatty acid esters are essentially insoluble in water. In view of the chemical similarities, it is therefore likely that sterols sharing this chemical nucleus will have similar properties when used in the vaccine compositions of the present invention. Sterols are well known in the art and are commercially available. For example, cholesterol is reported in the Merck Index, 12aed., p. 369. Suitable sterols include, without limitation, β-sitosterol, stigmasterol, ergosterol, ergocalciferol, and cholesterol. Suitable saponins include triterpenoid saponins. These triterpoenoids are a group of surface-active glycosides of plant origin and share a common chemical core composed of a hydrophilic region (usually several sugar chains) together with a hydrophobic region of either steroid or triterpenoid structure. Because of these similarities, saponins that share this chemical core are likely to have similar builder properties. Triterpenoids suitable for use in the adjuvant compositions can be from many sources, either plant-derived or synthetic equivalents, including, but not limited to, Quillaja saponaria, tomatine, ginseng extracts, mushrooms, and a glycoside alkaloid structurally similar to steroidal saponins. If a saponin is used, the adjuvant compositions generally contain an immunologically active saponin fraction from the stem of Quillaja saponaria. The saponin can be, for example, Quil A or another purified or partially purified saponin preparation, which is commercially available. Thus, the saponin extracts can be used as mixtures or purified individual components such as QS-7, QS-17, QS-18 and QS-21. In one embodiment, Quil A is at least 85% pure. In other embodiments, Quil A has a purity of at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%. Quaternary amine compounds refer to ammonium-based compounds with four hydrocarbon groups. In practice, hydrocarbon groups are generally limited to alkyl or aryl groups. In a number of embodiments, quaternary amine compounds are composed of four alkyl chains, two of which are C10-C20 alkyls and the remaining two are C1-C4 alkyls. In a number of embodiments, the quaternary amine is bromide, chloride, or a pharmaceutically acceptable counterion of dimethyldioctadecylammonium (DDA). ri ocnn / i ζηζ / Ε / γίΛΐ The appropriate glycolipids are generally those that activate the Th2 response. Glycolipids include, without limitation, those encompassed by Formula I and described generally in US Publication 20070196384 (Ramasamy et al). Al QCnn / l 7Α7 / Β / ΥΙΛΙ R5—O—CH2 In the structure of formula I, R1 and R2 are independently hydrogen or a saturated alkyl radical having up to 20 carbon atoms; X is -CH2-, -O- or -NH-; R2 hydrogen or a saturated or unsaturated alkyl radical having up to 20 carbon atoms; R3, R4 and R5 are independently hydrogen, -SO42', -PO42', -CO-Ci-10 alkyl; R6 is L-alanyl, L-alpha-aminobutyl, L-arginyl, L-asparginyl, L-aspartyl, L-cysteinyl, L-glutamyl, L-glycyl, L-histidyl, L-hydroxyprolyl, Lysoleucyl, L-leucyl, L -lysyl, L-methionyl, L-ornithinyl, L-phenylalanyl, L-prolyl, L-seryl, L-threonyl, L-tyrosyl, L-tryptophanyl and L-valyl or their D-isomers. In a number of embodiments, the suitable glycolipid is N-(2-deoxy-2-L-leucylaminob-D-glucopyranosyl)-N-octadecyldodecanoylamide or an acetate thereof. Aluminum is a known builder or component of builder formulations and is commercially available in forms such as Reheis, Inc, Brentag alhydrogel REHYDRAGEL® or VAC 20® wet gel. REHYDRAGEL® is a crystalline aluminum oxyhydroxide, known mineralogically as boehmite. It is effective in vaccines when there is a need for binding to negatively charged proteins. The AI2O3 content varies from 2% to 10% depending on the grade, and its viscosity is 1000-1300 cP. In general, it can be described as an absorbent aluminum hydroxide gel. VAC® 20 Moist Gel is a white to off-white, translucent, viscous colloidal gel. In certain embodiments, the AI2O3 content is about 2% w / v. In other embodiments, the aluminum source can also be prepared by precipitated aluminum hydroxide processes. In certain series of embodiments, in addition to the oil and one or more optional emulsifiers, the adjuvant formulations also comprise (or consist essentially of, or consist of) a combination of monophosphoryl-lipid A (MPL-A) or an analogue of monophosphoryl lipid A (MPL-A). itself, a steral and an immunostimulatory oligonucleotide. Adjuvants containing these ingredients are called TCMO. The TCMO adjuvant can also optionally include poly I:C (TCMYO) and / or a saponin. Thus, adjuvant formulations that comprise, or consist essentially of, or consist of, a combination of monophosphoryl-lipid A (MPL-A) or an analogue thereof, a steral and an immunostimulatory oligonucleotide, and saponin are referred to as QTCMO. In addition, adjuvant formulations can also include poly I:C. Said adjuvants are called QTCMYO. In a number of embodiments, the TCMO adjuvants comprise light mineral oil in an amount of 40% to 50% v / v of the total volume of the vaccine composition. Emulsions include TWEEN-80 and SPAN-80, total amount from 0.1% to 40% v / v of the total volume of the vaccine composition, provided that the sorbitan monooleate and oil together comprise about 50.5%. at 52% v / v of the composition. The immunostimulatory oligonucleotide is an ODN, preferably an ODN-containing palindrome, optionally with a modified backbone. In certain embodiments, a dose of TCMO contains between about 1 ug and about 400 ug of the immunostimulatory oligonucleotide, between about 1 ug and about 1000 ug of the ester, between about 0.1 ug and 500 ug of MPL-A or the analog thereof. . The amounts of other compounds per dose are selected based on the subject species. For example, in some embodiments suitable for adult cattle, sheep, or pigs, a dose of TCMO will contain between about 50 and 400 ug (for example, 50-300, or 100-250 ug, or about 50 to about 100 ug for adult pigs). , from about 100 to about 250 ug for cattle) of the immunostimulatory oligonucleotide, between about 100 and about 1000 ug (for example, 200-1000, 250-700 ug, or about 400-500 ug) of the steral, such as cholesterol, and between about 5 and about 500 ug (eg, 5-100 ug, or 5-50 ug, or 10-25 ug) of MPL-A or the analog thereof. In some embodiments suitable for companion animals or piglets, a dose of TCMO will contain between about 5 and 100 ug (for example, 10-80, or 20-50 ug) of the immunostimulatory oligonucleotide, between about 5 and 100 ug (for example, 10-80, or 20-50 ug) of the steral such as cholesterol, and between about 0.5 and about 200 ug (for example, 1-100 ug, or 5-50 ug, or 5-20 ug) of MPL- A or the analogue thereof. In some poultry embodiments, a dose of TCMO adjuvant will contain between about 0.1 and about 5 ug (eg, 0.5-3 ug, or 0.9-1.1 ug) of immunostimulatory oligonucleotides, between about 0.5 and about 50 ug ( for example, 1-20 ug, or 1-10 ug) of the steral such as cholesterol and about 0.1 to 10 ug Al acnn / l 7Π7 / Β / ΥΙΛΙ (eg, 0.5-5 ug, or 1-5 ug) of MPLA or the analogue thereof. ). The MPL-A is present in an amount of 0.lug / dose to 2,000 ug / dose. In certain embodiments, TCMO adjuvants are prepared as follows: a) Sorbitan monooleate, MPL-A and cholesterol are dissolved in light mineral oil. The resulting oil solution is sterile filtered; b) Immunostimulatory oligonucleotide and polyoxyethylene (20) sorbitan monooleate are dissolved in aqueous phase, thus forming the aqueous solution; c) The aqueous solution is added to the oil solution with continued homogenization, thus forming the TCMO adjuvant formulation. In TCMYO adjuvants, cholesterol, oil, optional emulsifiers, MPL-A and immunostimulatory oligonucleotides are present as in the TCMO adjuvant formulation for the respective species. Poly I:C may be present, in general, in the amount between about 1 ug and about 100 ug per dose. More specifically, poly I:C may be present in an amount of 5-100 ug per dose (eg, 5-50 ug, or 10-30 ug) in certain embodiments suitable for cattle, adult pigs, or sheep. In certain embodiments suitable for companion animals or piglets, a dose of TCMYO contains between about 1 and about 50 ug (eg, 5-50 ug, or 10-20 ug) of poly I:C. In certain embodiments suitable for poultry vaccines, a dose of TCMYO contains between about 1 and about 10 ug (eg, 1-5 ug, or 3-5 ug) of poly I:C. In certain embodiments, TCMYO adjuvants are prepared similarly to TCMO adjuvants, and the poly I:C is added to the aqueous solution. In a number of embodiments, in QTCMO adjuvants, the cholesterol, oil, optional emulsifiers, MPL-A and immunostimulatory oligonucleotides are present as in the TCMO adjuvant formulation for the respective species. A saponin is preferably Quil A or a purified fraction thereof, and may be present in amounts between about 0.1 ug and about 1000 ug per dose. More specifically, the saponin may be present in an amount of 0.1-5 ug per 50 ul of the vaccine composition (for example, 0.5-30 ug per 50 ul of the composition, or more preferably 1-10 ug) per doses in certain modalities for vaccines for poultry. In certain embodiments suitable for companion animal and piglet applications, the saponin, for example Quil A or a purified fraction thereof, is present in amounts between about 10 and about 100 ug per dose (eg 10-50 ug or 20-50 ug per dose). In certain embodiments suitable for cattle, adult pigs or sheep, the saponin, such as Quil A or a purified fraction thereof, ri acnn / i znz / R / YiAi is present in an amount between about 100 and about 1000 ug per dose (eg, 200-800 ug or 250-500 ug per dose). In certain embodiments, QTCMO adjuvants are prepared similarly to TCMO adjuvants, and the saponin is added to the aqueous solution. In a number of embodiments, in QTCMYO adjuvants, the saponin is present as in QTCMO adjuvant and all other ingredients are present as in TCMYO, for the respective species. In certain embodiments, QTCMYO adjuvants are prepared similarly to TCMYO adjuvants, and the saponin is added to the aqueous solution. In alternative embodiments, in addition to the oil and optional emulsifier(s), adjuvant formulations also comprise (or consist essentially of, or consist of) a combination of monophosphoryl-lipid A (MPL-A) or an analogue thereof and a polycationic carrier . These adjuvants are called XOM. In a number of embodiments, in XOM adjuvants for companion animals or piglets, the polycation vehicle is present in an amount of 1-50 mg per dose (eg, 1-25 mg per dose, or 10-25 mg per dose). , and the MPL-A or analog thereof is present in an amount between about 1 and 50 ug per dose (eg, 1-25 ug per dose, or 10-25 ug per dose). In certain embodiments suitable for adult cattle, sheep, and swine, the polycation vehicle is present in an amount of between about 5 and about 500 mg per dose (for example, 10-500 mg, or 10-300 mg, or 50-200 mg per dose) and the MPL-A or analog thereof is present in an amount of between about 1 and about 100 ug per dose (for example, 5-100 ug, or 5-50 ug, or 10-30 ug). . In certain embodiments suitable for companion animals and piglets, the polycationic carrier is present in an amount of from about 1 to about 50 mg per dose (eg, 1-25 mg per dose, or 10-25 mg per dose), and the MPL-A or the analog thereof is present in an amount of between about 0.5 and about 200 ug (eg, 1-100 ug, or 5-50 ug, or 5-20 ug) per dose. In certain embodiments suitable for poultry vaccines, the polycationic carrier is present in an amount between 0.5 and 25 mg per dose (eg, 120 mg, or 1-10 mg, or 5-10 mg) and the MPL- A or the analogue thereof is present in an amount between about 0.5 and 10 ug per dose (for example, 1-10 ug, or 1-5 ug, or 2-5 ug). In certain embodiments, XOM adjuvants are prepared as follows: a) Sorbitan monooleate, MPL-A and cholesterol are dissolved in light mineral oil. The resulting oil solution is sterile filtered; Al ocnn / l 7Π7 / Β / ΥΙΛΙ b) DEAE-dextran and polyoxyethylene (20) sorbitan monooleate are dissolved in aqueous phase, thus forming the aqueous solution; c) The aqueous solution is added to the oil solution with continued homogenization, thus forming the XOM adjuvant formulation. In further alternative embodiments, in addition to the oil and emulsifier(s), adjuvant formulations also comprise (or consist essentially of, or consist of) a combination of an immunostimulatory oligonucleotide and a polycationic vehicle, provided that if said vehicle polycation is DEAE-dextran, then the antigen is not E. coli J-5 bacterin. These adjuvants are called TXO. In certain embodiments, TXO-adjuvanted vaccines contain antigen(s) comprising pathogens affecting cattle, sheep, horses, or pigs. In other embodiments, the antigens are derived from said pathogens. In other embodiments, TXO-adjuvanted vaccines contain antigen(s) comprising pathogens affecting poultry or cats, or the antigens may be derived from such pathogens. In a number of embodiments, the TXO adjuvants can also include a source of aluminum, such as an AI(OH)3 gel. TXO adjuvants with aluminum are called TXO-A. In a number of embodiments, in TXO adjuvants, the immunostimulatory oligonucleotide, preferably an ODN, preferably containing a palindromic sequence, and optionally with a modified backbone, may be present in an amount of 0.5-400 ug per dose, and the polycationic carrier it may be present in an amount of 0.5-400 mg per dose. The dosages vary depending on the target species. For example, in certain embodiments suitable for adult cattle, sheep, or swine, a dose of TXO will comprise between about 50 and 400 ug (for example, 50-300, or 100-250 ug, or about 50 to about 100 ug for adult pigs and about 100 to about 250 ug for cattle) of the immunostimulatory oligonucleotide, and the polycationic carrier may be present in an amount of between about 5 and about 500 mg per dose (eg, 10-500 mg, or 10- 300 mg, or 50-200 mg per dose). In certain embodiments suitable for companion animals or piglets, a dose of TXO will comprise between about 5 and 100 ug (for example, 10-80 ug, or 20-50 ug) of the immunostimulatory oligonucleotide, while the polycationic vehicle may be present in an amount of 1-50 mg per dose (for example, 1-25 mg per dose, or 10-25 mg per dose). In certain embodiments suitable for poultry, a dose of TXO adjuvant will comprise between about 0.1 and about 5 ug (for example, To acnn / l 7Π7 / Β / ΥΙΛΙ 0.5-3 ug, or 0.9-1.1 ug) of the immunostimulatory oligonucleotide, and the polycationic carrier may be present in an amount between 0.5 and 25 mg per dose (for example, 1-20 mg, or 1-10 mg or 5- 10mg). In certain embodiments, TXO adjuvants are prepared as follows: a) Sorbitan monooleate is dissolved in light mineral oil. The resulting oil solution is sterile filtered; b) Immunostimulatory oligonucleotide, DEAE-dextran and polyoxyethylene (20) sorbitan monooleate are dissolved in aqueous phase, thus forming the aqueous solution; and c) The aqueous solution is added to the oil solution with continued homogenization, thus forming the TXO adjuvant formulation. In a number of embodiments, in TXO-A adjuvants, the immunostimulatory oligonucleotide is present as in TXO adjuvant, the aluminum source is present in an amount up to 40% v / v (eg, 35%, 30% , 25%, 20%, 15%, 10%, 5%, 1%). In a number of embodiments, the aluminum source is present at 2-20% v / v of the vaccine composition, more preferably between about 5% and about 17% v / v. In certain embodiments, TXO-A builders are prepared in a similar way to TXO builders, and the aluminum source is added to the aqueous solution. In additional embodiments, the adjuvants of the present invention contain the oil, optional emulsifier(s), immunostimulatory oligonucleotide, and aluminum source. These compounds are present in the ranges reported for the TXO-A adjuvant, except that the polycationic carrier is absent in TOA. The TOA adjuvant is prepared similarly to the TXO adjuvant, except that the aqueous phase contains the aluminum source instead of DEAE-dextran. In certain embodiments, in addition to the oil and emulsifier(s), formulation adjuvants also comprise (or consist essentially of, or consist of) a combination of a polycationic carrier and an aluminum source. This adjuvant is called AXO. These compounds may be present in amounts similar to those present in a TXO-A adjuvant for the respective species, and the AXO adjuvant may be prepared similarly to TXO-A, but without the addition of the immunostimulatory oligonucleotide. In certain embodiments, in addition to the oil and emulsifier(s), formulation adjuvants also comprise (or consist essentially of, or consist of) a combination of a saponin and a sterol. This adjuvant is called QCO. The nature and amounts of the QCO ingredients are similar to the amounts of the saponin, sterol, oil and emulsifier(s) in the QTCMO adjuvant. QCO can be prepared by adding a Al acnn / l 7Π7 / Β / ΥΙΛΙ aqueous solution comprising the saponin, the ester and, preferably, the water-soluble emulsifier in an oily phase, comprising the oil and, preferably, the oil-soluble emulsifier with continuous homogenization. In still other alternative embodiments, in addition to the oil and emulsifier(s), formulation adjuvants also comprise (or consist essentially of, or consist of) a combination of a quaternary amine, glycolipid, MPL-A or analog thereof, and poly I:C. These adjuvants are called ODYRM. In ODYRM adjuvants, the oil is generally a mixture of phospholipids such as phosphatidyl cholines. AMPHIGEN® is a suitable example of such an oil, and would be present in an amount similar to the amount of oil as described above. In a number of embodiments, in ODYRM adjuvants, the quaternary amine, eg, DDA, is present in an amount between about 1 ug and about 200 ug per dose, the poly I:C is present in an amount between about 0.5 ug and 100 ug per dose, the glycolipid is present in an amount between about 0.5 ug and about 2000 ug per dose and the MPL-A or analog thereof is present in an amount between about 0.5 ug and 100 ug per dose . More specifically, in certain embodiments suitable for administration to cattle, adult pigs, or sheep, the quaternary amine may be present in an amount of from about 50 ug to about 200 ug per dose (eg, 50-150 ug, or about 100 ug). , the poly I:C may be present in amounts between about 1 ug and about 100 ug per dose (for example, 1-50 ug or 5-50 ug), the glycolipid may be present in an amount between about 500 ug and about 2000 ug per dose (for example, 500-100 ug or about 1000 ug) and the MPLA or analog thereof may be present in an amount of between about 5 ug and about 100 ug per dose (for example, 5- 50 ug, or 10-50 ug). In certain embodiments suitable for administration to companion animals and piglets, the quaternary amine may be present in an amount of between about 5 and about 500 ug per dose (eg, 10-100 ug per dose, or 2050 ug per dose). , the poly I:C can be present in an amount between about 5 ug and about 25 ug per dose (for example, 50-20 ug, or about 10 ug), the glycolipid can be present in an amount between about 10 and about 100 ug per dose (for example, 20-100 ug or 25-50 ug) and the MPL-A or analog thereof may be present in an amount of between about 5 and about 50 ug per dose (for example, 520 ug, or 10-20 ug). In certain other embodiments, suitable for poultry vaccines, ri ocnn / i znz / E / YiAi a dose will contain between about 1 ug and about 10 ug of the quaternary ammonium compound (for example, 5-10 ug, or about 5 ug), between about 0.5 and about 10 ug of poly I:C (for example, 1-10 ug or 1-5 ug), between about 0.5 and 10 ug of the glycolipid (for example, 1-10 ug or 5-10 ug or 1-5 ug) and between about 0.5 ug and about 5 ug of MPL-A or the analog thereof (eg, 0.5-5 ug or 1-5 ug). In certain embodiments, ODYRM adjuvants are prepared as follows: a) Sorbitan monooleate, MPL-A are dissolved in light mineral oil. The resulting oil solution is sterile filtered and dispersed in water with some surfactant, ethanol and acetic acid; b) Polyoxyethylene (20) sorbitan monooleate, quaternary amine, eg DDA, and poly I:C are dissolved in the aqueous phase, thus forming the aqueous solution; and c) The aqueous solution is added to the oil solution with continued homogenization, thus forming the ODYRM adjuvant formulation. In yet another series of embodiments, in addition to the oil and emulsifier(s), formulation adjuvants also comprise (or consist essentially of, or consist of) a combination of a saponin, a sterol, a quaternary amine, a polycationic carrier, with the provided that if said polycationic carrier is DEAE-dextran, then the antigen is not E. coli J-5 bacterin. These adjuvants are called QCDXO. In QCDXO adjuvants, in certain embodiments, saponin, eg, Quil A may be present in amounts between about 0.1 ug and about 1000 ug per dose, sterol, eg cholesterol, is present between about 1 ug and about 1000 ug per dose, the quaternary amine, eg DDA, is present in an amount of between about 1 ug and about 200 ug per dose and the polycationic carrier may be present in an amount of 0.5-400 mg per dose. The dosages vary depending on the target species. In certain embodiments suitable for adult cattle, sheep, and swine, the saponin is present in an amount of between about 100 and about 1000 ug per dose (for example, 200-800 ug, or 250-500 ug per dose), the sterol is present in amounts between about 100 and about 1000 ug (for example, 200-1000, 250-700 ug, or about 400-500 ug), the quaternary amine may be present in an amount between about 50 ug and about 200 ug per dose (eg, 50-150 ug, or about 100 ug) and the polycationic carrier may be present in an amount of between about 5 and about 500 mg per dose (eg, 10-500 mg, or 10- 300 mg, or 50-200 mg per dose). Ei ocnn / i znz / E / YiAi In certain embodiments suitable for companion animal and piglet applications, the saponin, for example Quil A or a purified fraction thereof, is present in amounts of between about 10 and about 100 ug per dose (for example, 10-50 ug or 20-50 ug per dose), the steral is present in amounts between about 5 and 100 ug (for example, 10-80, or 20-50 ug), the quaternary amine can be present in an amount between about 5 and about 500 ug per dose (for example, 10-100 ug per dose, or 20-50 ug per dose) and the polycationic carrier may be present in an amount of 1-50 mg per dose (for example, 1-25 mg per dose, or 10-25 mg per dose. In some embodiments suitable for poultry vaccines, the saponin may be present in an amount of 0.1-5 ug per 50 ul of the vaccine composition (for example, 0.5-30 ug per 50 ul of the composition, or more preferably 1-10 ug) per dose, the steral may be present in amounts between about 0.5 and about 50 ug (for example, 1-20 ug, or 1-10 ug), the quaternary amine may be present in an amount between about 5 and about 500 ug per dose (for example, 10-100 ug per dose, or 20-50 ug per dose) and the polycationic carrier may be present in an amount between 0.5 and 25 mg per dose (for example, 1-20mg, or 1-10mg or 5-10mg). In certain embodiments, QCDXO adjuvants are prepared as follows: a) Sorbitan monooleate is dissolved in oil. The resulting oil solution is sterile filtered; b) Polyoxyethylene (20) sorbitan monooleate, quaternary amine, for example DDA, the polycationic vehicle, the ester and the saponin are dissolved in the aqueous phase, thus forming the aqueous solution; and c) The aqueous solution is added to the oil solution with continued homogenization, thus forming the adjuvant formulation QCDXO. Sometimes it is impossible or impractical to concentrate the antigen, particularly in commercial scale applications and low concentrations of antigen solutions have to be used. Thus, in some embodiments, the vaccine compositions of the present invention comprise the adjuvant formulations described above, wherein the oil phase content in these adjuvant formulations is dilute, and wherein the vaccine composition is a water-in-water emulsion. oil. In practice it is possible to create a water-in-oil emulsion in which the oil phase is less than 50% v / v. Briefly, first, the adjuvant formulation of the present invention is prepared as described above. In said adjuvant formulation, the oily phase ri ocnn / i znz / E / YiAi comprises more than 50% v / v of the adjuvant formulation. The amounts of ingredients other than oil and emulsifier(s) are increased respectively based on the final target concentration and the desired dilution. For example, if it is intended to prepare a vaccine composition in which the adjuvant formulation comprises 80% v / v, the amounts of ingredients other than oil are increased by a factor of 1.25 (1 / 0.8). The amounts of emulsifiers, if any, (for example, TWEEN®80 and / or SPAN®80) do not necessarily need to be increased, but preferably, the volume ratio between the oil and the emulsifier(s) is kept the same in the adjuvant formulation. and in the final vaccine composition. The antigen solution is then added to the adjuvant formulation. The integrity of water-in-oil emulsions can be maintained as long as the dispersed spherical water droplets are not present in a more concentrated form than the maximum packing fraction for random packing of monodisperse droplets, ie: 0.64. See Tadros, Emulsion Formation, StabiHty and Rheotogy, Iaed. 2013, Wiley-VCH GmbH & Co KGaA. As long as the total volume fraction occupied by the aqueous droplets does not exceed 0.64, that is: 64% v / v. Conversely, this implies that the oil phase should not be less than 36% v / v. Accordingly, in different embodiments of this aspect of the invention, vaccine formulations are provided comprising the antigenic compound and the adjuvant formulation diluted according to the previously described embodiments, wherein the oil phase comprises more than 36% of the vaccine composition v / v, and wherein the vaccine composition is a water-in-oil emulsion. Without limitation, adjuvant formulations suitable for this aspect of the invention include TCMO, TCMYO, QTCMO, QTCMYO, XOM, TXO, TXO-A, TAO, AXO, QCO, ODYRM, QCDXO. The volume of the oily phase is, in different modalities, 37% v / v, 38% v / v, 39% v / v, 40% v / v, 41% v / v, 42% v / v, 43 % v / v, 44% v / v, 45% v / v, 46% v / v, 47% v / v, 48% v / v, 49% v / v or 50% v / v of the composition of vaccine. The concentration of the oily phase should be high enough to create a depot effect and protect the antigen and immunomodulator(s) from rapid degradation by the host's immune system, preferably 20% or more v / v of the vaccine composition. Accordingly, in another aspect, in the vaccine compositions of the present invention, the amounts of the oil phase in the adjuvant formulations are diluted so that the vaccine formulation is in the oil-in-water emulsion or in the oil-in-water emulsion. water-in-oil, the oily phase comprising 20% or more v / v of the vaccine composition. The amounts of ingredients other than oil and emulsifiers are increased respectively based on the final target concentration and the desired dilution. For example, for When acnn / l 7Π7 / Β / ΥΙΛΙ prepare a vaccine composition in which the adjuvant formulation comprises 33.3% v / v, the amounts of ingredients other than oil and emulsifier(s) are increased by a factor of 3 (1 / 0.333). The amounts of emulsifiers, if any, (for example, TWEEN®80 and / or SPAN®80) do not need to be increased, but preferably, the volume ratio between the oil and the emulsifier(s) is kept the same in the adjuvant formulation and in the final vaccine composition. In different embodiments, the vaccine composition is an oil-in-water emulsion or a water-in-oil-in-water emulsion, wherein the oil phase comprises 21% v / v, 22% v / v, 23% v / v , 24% v / v, 25% v / v, 26% v / v, 27% v / v, 28% v / v, 29% v / v, 30% v / v, 31% v / v, 32 %v / v, 33%v / v, 34%v / v, 35%v / v, 36%v / v, 37%v / v, 38%v / v, 39%v / v, 40%v / v, 41% v / v, 42% v / v, 43% v / v, 44% v / v, 45% v / v, 46% v / v, 47% v / v, 48% v / v , 49% v / v or 50% v / v of the vaccine composition. Adjuvant formulations for this aspect of the invention include TCMO, TCMYO, QTCMO, QTCMYO, XOM, TXO, TXO-A, TAO, AXO, QCO, ODYRM, QCDXO, provided that the oil phase of the adjuvant formulation can be less than 50% v / v, but greater than 20% v / v of the final vaccine composition. Antigens v diseases The compositions may contain one or more antigens. The antigen can be any of a wide variety of substances capable of producing a desired immune response in a subject, including, without limitation, one or more of viruses (inactivated, attenuated, and live modified), bacteria, parasites, nucleotides (including, but not limited to limitation, nucleic acid-based antigens, e.g. DNA vaccines), polynucleotides, peptides, polypeptides, recombinant proteins, synthetic peptides, protein extract, cells (including tumor cells), tissues, polysaccharides, carbohydrates, fatty acids, teikioco acid, peptidoglycans, lipids or glycolipids, individually or in any combination thereof. Antigens used with the adjuvants of the invention also include immunogenic fragments of nucleotides, polynucleotides, peptides, polypeptides, which can be isolated from the organisms referred to herein. Live, modified live, and attenuated virus strains that do not cause disease in a subject have been isolated in avirulent form or have been attenuated using procedures well known in the art including serial passage in a suitable cell line or exposure to ultraviolet light. or a chemical mutagen. Inactivated or killed virus strains are those that have been inactivated by methods well known to those skilled in the art, including formalin treatment, betapropriolactone (BPL), binary ethyleneimine (BEI), radiation The acnn / l 7Π7 / Ε / ΥΙΛΙ sterilizing, heat or other procedures of this type. Two or more antigens can be combined to produce a polyvalent composition that can protect a subject against a wide variety of diseases caused by the pathogens. Currently, commercial vaccine manufacturers, as well as end users, prefer multivalent vaccine products. Although conventional adjuvants are often limited in the variety of antigens with which they can be used effectively (either monovalently or polyvalently), the adjuvants described herein can be used effectively with a wide range of antigens, both monovalently and polyvalently. . Thus, the antigens described herein can be combined in a single composition comprising the adjuvants described herein. Some examples of bacteria that can be used as antigens with the adjuvant compositions include, but are not limited to, Aceinetobacter calcoaceticus, Acetobacter passeruianus, Actinobacillus pleuropneumoniae, Aeromonas hydrophila, Alicyclobacillus acidocaldarius, Arhaeglobus fulgidus, Bacillus pumilus, Bacillus stearothermophillus, Bacillus subtilis, Ba cillus thermocatenulatus, Bordetella septic bronchitis, Burkholderia cepacia, Burkholderia glumae, Campylobacter coli, Campylobacter fetus, Campylobacter jejuni, Campylobacter hyointestinalis, Chlamydia psittaci, Chlamydia trachomatis, Chlamydophila spp., Chromobacterium viscosum, Erysipelothrix rhusiopathieae, Listeria mono cytogenes, Ehrlichia canis, Escherichia coli, Haemophilus influenzae, Haemophilus somnus, Helicobacter suis, Lawsonia intracellularis, Legionella pneumophilia, Moraxellsa sp., Mycobactrium bovis, Mycoplasma hyopneumoniae, Mycoplasma mycoides subsp. mycoides LC, Clostridium perfringens, Odoribacter denticanis, Pasteurella (Mannheimia) haemolytica, Pasteurella multocida, Photorhabdus luminescens, Porphyromonas gulae, Porphyromonas gingivalis, Porphyromonas salivosa, Propionibacterium acnes, Proteus vulgaris, Pseudomonas wisconsinensis, Pseudomonas aeruginosa, Pseudomonas fluorescens C9, Pseudomonas fluorescens SIKW1, Pseudomonas Fragi, Pseudomonas luteola, pseudomonas oleovorans, pseudomonas sp Bll-1, alkaliges eutrophus, psychrobacter immobilis, rickettsia prowazekii, rickettsia rickettsia, all sexological varieties of salmonella enteric, which include, for example: SALMONELLA Entrico Typhimurium, Salm OONGORI EASTOI, SALMONELLA enterica Dublin, Salmonella enterica Choleraseuis and Salmonella enterica Newport, Serratia marcescens, Spirlina platensis, Staphlyoccocus aureus, Staphyloccocus epidermidis, Staphylococcus hyicus, Streptomyces albus, Streptomyces cinnamoneus, Streptococcus uberis, Streptococcus suis, Streptomyces exfoliates , Streptomyces scabies, Sulfolobus acidocaldarius, Syechocystis sp. , Vibrio cholerae, Borrelia burgdorferi, Treponema denticola, Treponema minutum, Treponema phagedenis, Treponema refringens, Treponema vincentii, Treponema palladium, Trueperella pyogenes and Leptospira species, such as the known pathogens Leptospira canicola, Leptospira grippotyposa, Rl ocnn / l 7Π7 / Β / ΥΙΛΙ Leptospira hardjo, Leptospira borgpetersenii hardjo-bovis, Leptospira borgpetersenii hardjo-prajitno, Leptospira interrogans, Leptospira icterohaemorrhagiae, Leptospira Pomona and Leptospira Bratislava and combinations thereof. Both inactivated virus and live attenuated virus can be used in the adjuvant compositions. Some examples of viruses that can be used as antigens include, but are not limited to, avian herpesvirus, bovine herpesvirus, canine herpesvirus, equine herpesvirus, feline viral rhinotracheitis virus, Marek's disease virus, ovine herpesvirus, porcine herpervirus, diarrhea virus (PEDv), pseudorabies virus, avian paramizovirus, bovine respiratory syncytial virus, canine distemper virus, canine parainfluenza virus, canine adenovirus, canine parvovirus, bovine parainfluenza virus 3, ovine parainfluenza virus 3, rinderpest virus, virus Border Disease Virus, Bovine Viral Diarrhea Virus (BVDV), BVDV Type I, BVDV Type II, Classical Swine Fever Virus, Avian Leukosis Virus, Bovine Immunodeficiency Virus, Bovine Leukosis Virus , bovine tuberculosis, equine infectious anemia virus, feline immunodeficiency virus, feline leukemia virus (FeLV), Newcastle disease virus, ovine progressive pneumonia virus, ovine lung adenocarcinoma virus canine coronavirus (CCV), CCV pantropic, canine respiratory coronavirus, bovine coronavirus, feline calicivirus, feline enteric coronavirus, feline infectious peritonitis virus, porcine epidemic diarrhea virus, porcine hemagglutinating encephalomyelitis virus, porcine parvovirus, porcine circovirus (PCV) type I, PCV of type II, porcine reproductive and respiratory syndrome virus (PRRS), transmissible gastroenteritis virus, turkey coronavirus, bovine ephemeral fever virus, rabies, rotovirus, vesicular stomatitis virus, lentivirus, avian influenza, rhinovirus, Equine Influenza, Swine Influenza Virus, Dog Influenza Virus, Cat Influenza Virus, Human Influenza Virus, Eastern Equine Encephalitis Virus (EEE), Venezuela Equine Encephalitis Virus, West Nile Virus, western equine encephalitis virus, human immunodeficiency virus, human papilloma virus, varicella zoster virus, hepatitis B virus, rhinovirus, and measles virus, and combinations thereof. Examples of peptide antigens include Bordetella bronchiseptica p68, GnRH, IgE peptides, Fel di and cancer antigens and combinations thereof. Examples of other antigens include nucleotides, carbohydrates, lipids, glycolipids, peptides, fatty acids, lipoteichoic and teichoic acid, and peptidoglycans and combinations thereof. Some examples of parasites that can be used as antigens with the adjuvant compositions include, but are not limited to, Anaplasma, Fasciola hepatica (liver fluke), Coccidia, Eimeria spp., Neospora caninum, Toxoplasma gondii, Giardia, Dirofilaria (heartworm), Ancylostoma (hookworms). ), Cooperia, Haemonchus contortus (barbershop stick worm), Ostertagia ostertagi (stomach worm), Dictyocaulus viviparous (lungworms), ri acnn / i znz / E / YiAi Trypanosoma spp., Leishmania spp., Trichomonas spp., Cryptosporidium parvum, Babesia, Schistosoma, Taenia, Strongyloides, Ascaris, Trichinella, Sarcocystis, Hammondia and Isopsora and combinations thereof. External parasites are also contemplated, including, but not limited to, ticks, including Ixodes, Rhipicephalus, Dermacentor, Amblyomma, Boophilus, Hyalomma and Haemaphysalis species and combinations thereof. The amount of antigen used to induce an immune response will vary considerably depending on the antigen used, the subject, and the level of response desired, and can be determined by one of skill in the art. For vaccines containing modified live virus or attenuated virus, a therapeutically effective amount of the antigen will generally range from about 102 cell culture infective dose (TCID)50 to about 1010TCID50, inclusive. For many such viruses, a therapeutically effective dose is generally in the range of about 102TCID50 to about 108TCID50, inclusive. In some embodiments, therapeutically effective dose ranges are from about 103TCID50 to about 106TCID50, inclusive. In some of the other modalities, therapeutically effective dose ranges are from about 104TCID50 to about 105TCID50, inclusive. For vaccines containing inactivated virus, a therapeutically effective amount of the antigen is generally at least about 100 relative units per dose, and often in the range of about 1,000 to about 4,500 relative units per dose, inclusive. In other embodiments, the therapeutically effective amount of the antigen is in the range of from about 250 to about 4,000 relative units per dose, inclusive, from about 500 to about 3,000 relative units per dose, inclusive, from about 750 to about 2,000 units. relative units per dose, inclusive, or from about 1,000 to about 1,500 relative units per dose, inclusive. A therapeutically effective amount of antigen in vaccines containing inactivated virus can also be measured in terms of relative potency (RP) per ml. A therapeutically effective amount is often in the range of about 0.1 to about 50 RP per mole, inclusive. In other embodiments, the therapeutically effective amount of the antigen is in the range of from about 0.5 to about 30 PR per mL, inclusive, from about 1 to about 25 PR per mL, inclusive, from about 2 to about 20 PR per mL. , inclusive, from about 3 to about 15 RP per mi, inclusive, or from about 5 to about 10 RP per mi, inclusive. The number of cells for a bacterial antigen administered in a vaccine varies Ei acnn / i znz / E / YiAi from about 1 x 106 to about 5 x 1010 colony forming units (CFU) per dose, inclusive. In other embodiments, the number of cells ranges from about 1 x 107 to 5 x 1010 CFU / dose, inclusive, or from about 1 x 108 to 5 x 1010 CFU / dose, inclusive. In still other modalities, the number of cells ranges from approximately 1 x 102 to 5 x 1010CFU / dose, inclusive, or from approximately 1 x 104 to 5 x 109CFU / dose, inclusive, or from approximately 1 x 105 to 5 x 109CFU / dose. , inclusive, or approximately 1 x 106 to 5 x 109CFU / dose, inclusive, or approximately 1 x 106 to 5 x 108CFU / dose, inclusive, or approximately 1 x 107 to 5 x 109CFU / dose, inclusive. The number of cells for a parasitic antigen administered in a vaccine ranges from about 1 x 102 to about 1 x 1010 per dose, inclusive. In other embodiments the number of cells ranges from about 1 x 103 to about 1 x 109 per dose, inclusive, or from about 1 x 104 to about 1 x 108 per dose, inclusive, or from about 1 x 105 to about 1 x 107 per dose, both inclusive, or from about 1 x 106 to about 1 x 108 per dose, inclusive. It is well known in the art that with conventional adjuvants a substantially higher amount of inactivated virus than live modified or attenuated virus is required to stimulate a comparable level of serological response. However, it has surprisingly been found that with the adjuvant compositions described herein, approximately the same amounts of inactivated virus and modified live virus stimulate similar levels of serological response. In addition, smaller amounts of live modified, attenuated and inactivated virus with the adjuvants described herein are required compared to conventional adjuvants to achieve the same level of serological response. These unexpected findings demonstrate the conservation of resources and the reduction of costs during the preparation of immunogenic and vaccine compositions. For vaccines with broad utility, the manufacture of millions of doses per year is required, so these savings can be substantial. Composition Management Dose sizes of the compositions typically range from about 1 ml to about 5 ml, inclusive, depending on the subject and antigen. For example, for a canine or feline, a dose of about 1 ml is normally used, while in cattle a dose of 2-5 ml is normally used. However, these adjuvants can also be formulated in microdoses, in which doses of 100 mui can be used. Routes of administration for the adjuvant compositions include the Al QCnn / l 7Α7 / Β / ΥΙΛΙ administration parenteral, oral, oronasal, intranasal, intratracheal, topical, subcutaneous, intramuscular, transcutaneous, intradermal, intraperitoneal, intraocular, intravenous and in the pessary. Any suitable device can be used to administer the compositions, including syringes, droppers, needle-free injection devices, patches, and the like. The route and device selected for use will depend on the composition of the adjuvant, the antigen and the subject, and are well known to the skilled person. Use of compositions One of the requirements for any vaccine adjuvant preparation for commercial use is to establish the stability of the adjuvant solution for prolonged storage periods. Adjuvant formulations are provided herein that are easy to manufacture and stable for at least 18 months. In one embodiment, the formulations are stable for approximately 18 months. In another embodiment, the formulations are stable for between about 18 to about 24 months. In one embodiment, the formulations are stable for approximately 24 months. Accelerated test procedures also indicate that the formulations described herein are stable. An advantageous feature of the present adjuvant compositions is that they can be safely and effectively administered to a wide range of subjects. Combinations of builders are expected in the art to show more reactogenicity than individual components. However, the compositions described herein show reduced reactogenicity compared to compositions in which any one or two of the components are used, while the adjuvant effect is maintained. It has also surprisingly been shown that the adjuvant compositions described herein show improvements in safety compared to other adjuvant compositions. The adjuvant compositions described herein are useful for inducing a desired immune response in a subject. They are effective in multiple species. A suitable subject is any animal for which administration of an adjuvant composition is desired. Includes mammals and non-mammals, including primates, livestock, companion animals, laboratory test animals, captive wild animals, birds (including embryos), reptiles, and fish. Thus, this term includes, but is not limited to, monkeys, humans, pigs, cattle, sheep, goats, equines, mice, rats, guinea pigs, hamsters, rabbits, felines, canids, chickens, turkeys, ducks, other poultry. , frogs and lizards. The adjuvants described herein can be used to show serological differentiation between infected and vaccinated animals. Thus, it can be used in a commercial vaccine in which the antigen present in the vaccine triggers in the vaccinated animals a Al QCnn / l 7Α7 / Β / ΥΙΛΙ antibody pattern different from wild-type virus. A commercial vaccine is generally used in conjunction with a companion diagnostic assay that measures the difference in antibody patterns and shows which animals have been vaccinated and which animals are infected with wild-type virus. Such technology is useful in the control and eradication of viruses from a target population. The present invention also provides novel vaccine compositions useful in protecting against infection and disease caused by Nipah virus and / or Hendra virus, using Hendra virus G protein-provided antigen (and fragments, dimers, multimers and modified forms). thereof), all of which are adjuvanted as described herein. In certain embodiments, the builder is selected from the group consisting of TXO, TAO, and TXO-A. Such vaccines are useful in preventing infection and disease in, for example, horses, dogs, pigs, and humans. In the most preferred embodiment, both pigs and dogs are protected from both the Hendra virus and the Nipah virus. Recurrent NiV outbreaks resulting in significant numbers of human deaths have been problematic recently, eg Butler, Nature, vol. 429, at page 7 (2000); and Gurley et al., Emerging Infectious Diseases, vol. 13(7), p. 1031-1037 (2007). Case studies have associated disease in humans with zoonotic transmission from pigs, see Parashar et al., 1 Infect. Dis. vol 181, p. 1755-1759 (2000). Hendra virus has been clearly associated with deaths in humans, through transmission from horses. There is currently a licensed vaccine for the prevention of infection or disease caused by Hendra virus (Equivac® HeV; Zoetis) approved for use in horses, although there is no licensed vaccine to prevent infection with Nipah virus. There is still a need for Nipah virus or Hendra virus vaccines that can be clinically effective. Paramyxoviruses such as Hendra virus and Nipah virus possess two major membrane-anchored glycoproteins in the envelope of the virus particle. One glycoprotein is required for virion binding to receptors on host cells and is designated hemagglutinin-neuraminidase (HN) protein or hemagglutinin (H) protein, and the other is glycoprotein (G), which has neither hemagglutination nor neuraminidase activities. . Binding glycoproteins are type II membrane proteins, in which the amino (N) terminus of the molecule faces the cytoplasm and the carboxy (C) terminus of the protein is extracellular. The other major glycoprotein is the fusion (F) glycoprotein, which is a trimeric class I fusogenic envelope glycoprotein containing two heptad repeat (HR) regions and a hydrophobic fusion peptide. Hendra virus and Nipah virus infect cells through a pH-independent process of membrane fusion in recipient host cells through a concerted action. Al QCnn / l 7Α7 / Β / ΥΙΛΙ of its binding G glycoprotein and F glycoprotein following receptor binding. It has been suggested that the Hendra virus G glycoprotein could potentially cross-protect against Nipah virus infection and disease by K. Bossart et al., Journal of Virology, vol. 79, p. 6690-6702 (2005), and B. Mungall et al., Journal of Virology, vol. 80, p. 12293-12302 (2006). However, prior work does not provide vaccine compositions that are truly clinically effective, in this regard, for any mammalian species. Accordingly, the present invention encompasses an immunogenic composition comprising Hendra virus G protein, an adjuvant described in accordance with the practice of the present invention, and one or more excipients, in an amount effective to elicit clinically effective protection against Hendra virus and / or or Nipah. With respect to Hendra virus G glycoprotein polypeptides that are useful in the practice of the present invention, and recombinant expression thereof, reference is made to the entire disclosure of published international patent applications WO 2012 / 158643 and WO2006 / 085979, in which such information is clearly stated. Preferred examples of Hendra virus G protein polypeptides useful herein are disclosed in WO 2012 / 158643, and include, for example: full length G protein (SEQ ID NO:2 thereof); a soluble fragment thereof (encoding amino acids 73-604 of SEQ ID NO:2 of WO 2012 / 158643) and a further fragment disclosed therein having an Ig(kappa) leader sequence (SEQ ID NO: : 16 of WO 2012 / 158643). In general, soluble forms of the Hendra virus G glycoprotein comprise all or part of the ectodomain and are produced by deletion of all or part of the G glycoprotein transmembrane domain, and all or part of the cytoplasmic tail. Preferably, the coding gene sequence is codon-optimized for expression. In some embodiments, the Hendra G glycoprotein may be in dimeric and / or tetrameric form. Such dimers depend on the formation of disulfide bonds formed between cysteine residues in G glycoprotein. Such disulfide bonds may correspond to those formed in native G glycoprotein, or different disulfide bonds may form resulting in different dimeric and / or tetrameric forms. of G glycoprotein that enhance antigenicity. Additionally, neither dimerized nor tetramerized forms are also useful in accordance with the practice of the present invention, again taking into consideration that the G glycoprotein provides numerous conformation-dependent epitopes (i.e., generated from a tertiary three-dimensional structure) and that conservation of numerous such natural epitopes is therefore highly preferred for imparting a neutralizing antibody response. In general, the construction of expression vectors for Hendra G proteins can be as described in Example 1 of WO 2012 / 158643, with ai acnn / i znz / R / YiAi resulting protein expression from cells CHO as described in Example 2 hereof, or alternatively, using a vaccine system (see Example 3 hereof) or 293 cells (see Example 4 hereof). In a specific preferred example, the soluble G protein is provided as amino acids 73-604 of the native Hendra virus G glycoprotein (see SEQ ID NO: 2 of WO 2012 / 158643). Dimerization thereof occurs spontaneously, concomitant with expression from CHO cells, and the resulting G protein is approximately 50% dimer and 50% tetramer, with little monomer remaining. Expression in 293F cells leads to approximately 70% dimer. The resulting protein fractions are mixed with adjuvants as described throughout the present specification. As described in WO2012 / 158643, preferred doses of antigen for large animals are in the range of 50-200 micrograms per dose, with 100 micrograms being the most preferred dose. For small animals, such as dogs, smaller amounts are required, such as 25-50 micrograms, as will be appreciated by those skilled in the art. In addition, adjuvants can be used according to any of the modalities described above for the generation of diagnostic or therapeutic antibodies. In this aspect of the invention, an animal source is immunized with a formulation containing the adjuvant compositions of the present invention and an antigen. The choice of antigen is determined by the person needing to obtain such therapeutic or diagnostic antibodies and includes, without limitation, viruses, bacteria, viral particles, extracts, recombinant antigens, cell wall structures, and the like. Antigens may also include venoms for the preparation of snakebite medicines. Antigens suitable for this aspect of the invention may be of feline, canine, equine, porcine, bovine, ovine or avian origin. In certain embodiments, the antigen can be selected from FeLVgp70, bovine parainfluenza virus-3 BPI-3 (HN protein), HistophHus somni p31, Bordetella FHA, parapoxvirus, BVDV1 gp53, BVDV2 gp53, Clostridia toxins, canine circovirus , Brachyspira hyodysenteriae (pig species) antigens; inactivated whole cell and inactivated digestive pepsin. At a certain time after immunization, a source of antibodies is removed from the source animal (eg, mice, rats, hamsters, pigs, guinea pigs, rabbits, goats, sheep, poultry, cattle, horses). In certain other embodiments, the source animal is a cat or a dog. The source of antibodies ultimately depends on whether monoclonal or polyclonal antibodies are needed. For polycloning antibodies, the use of whey or milk may be considered. For monoclonal antibodies, spleen cells are a suitable source. Said antibodies can be used for diagnostic, research or Rl ocnn / l 7Π7 / Ε / ΥΙΛΙ therapeutics, including, without limitation, antivenoms, anti-transplant rejection drugs, serum neutralization assays, ELISA, ELISPOT, Western blots, cell-based assays, potency assays, and immunohistochemistry. Such antibodies provide monoclonal and polyclonal antibodies extracted from the source animal for use in diagnostic and therapeutic applications, including, without limitation, antivenoms, anti-transplant rejection drugs, serum neutralization assays, ELISAs, ELISPOTs, Western blots, based assays. in cells, potency assays and immunohistochemistry. In certain embodiments, immunizations with the compositions of the present invention will elicit sufficiently high serological titers to the desired antigen (greater than 1,000, or more preferably, greater than 5,000, or more preferably, greater than 10,000, or most preferably, greater than 50,000, or more preferably, more than 100,000, or more preferably, more than 250,000, or more preferably, more than 500,000, or more preferably, more than 1,000,000) in at least one animal (preferably at least 2 animals, or at least three animals, or in 50% of treated animals, or in at least 75% of treated animals, or, most preferably, in all treated animals), thus resulting in a sufficient amount of antibodies for diagnostic or screening applications. investigation. Antibodies of the immunoglobulin G (IgG) isotype are commonly used in these applications, although antibodies of other isotypes, eg, immunoglobulin M (IgM), may also be used. The source of antibodies ultimately depends on whether a polyclonal or monoclonal antibody is desired. For polyclonal antibodies, whey or milk can be used as the source of antibodies. For monoclonal antibodies, the appropriate antibody source is splenocytes. Further purification of the antibodies, if necessary, or preparation of monoclonal antibodies have been extensively described in the literature and one skilled in the art would not have undue difficulty in the modality of these procedures. In addition, the antibodies can be adapted to the target species, if necessary (eg, caninized or felinized). Again, the techniques for doing so are well known in the art and need not be described in the present application. Antibody Applications The antibodies would be suitable as reagents for serum neutralization assays, ELISAs, ELISPOTs, Western blots, cell-based assays, potency assays, and immunohistochemistry. These techniques are well known in the art. The antibodies of the present invention may also be used as therapeutic agents, eg, in transplant rejection, eg for the generation of anti-thymocyte globulin (ATG) agents. Currently, there are two agents of this type on the market: Ei ocnn / i znz / E / YiAi Atgam® and Thymoglobulin®. Procedures for making antithymocyte globulins have been generally described in US20040023340. It can also be used for the preparation of antidotes. In these embodiments, snake venom components would be used as antigens. Poisons and components thereof are also well known in the art. Animals of many species can be used as source animals, including, without limitation, poultry, mice, rats, hamsters, guinea pigs, rabbits, dogs, cats, sheep, goats, pigs, cattle, and equine species. The choice of the source animal depends on the task at hand and the judgment of the person skilled in the art. The specific non-limiting modalities are the following: In a first embodiment, the invention provides an adjuvant formulation comprising an oil phase and an aqueous phase, wherein the oil phase comprises at least 50% of the formulation v / v, said formulation comprising at least one monophosphoryl lipid. A (MPL-A) or an analogue thereof and an immunostimulatory oligonucleotide, provided that: a) if said immunostimulatory oligonucleotide is absent, then the formulation comprises: Yo. a poly I:C, a glycolipid and, optionally, a quaternary amine; or ii. a polycationic vehicle; b) if said monophosphoryl-lipid A (MPL-A) or the analog thereof is absent, then the formulation comprises a source of aluminium. In the second embodiment, the invention provides the adjuvant formulation of the first embodiment, wherein the immunostimulatory oligonucleotide, if present, is a CpG or oligoribonucleotide; the polycationic carrier, if present, is selected from the group consisting of dextran, DEAE-dextran (and derivatives thereof), PEG, guar gums, chitosan derivatives, polycellulose derivatives such as hydroxyethylcellulose (HEC), polyethyleneimene, polyaminos, and the quaternary amine, if present, is selected from the group consisting of DDA and avridine. In the third embodiment, the invention provides the adjuvant formulation according to the first or second embodiment, wherein the immunostimulatory oligonucleotide, if present, is CpG, the polycationic carrier, if present, is DEAE-dextran, and the quaternary amine. , if present, is DDA. In the fourth embodiment, the invention provides the adjuvant formulation according to any one of the first to third embodiments, wherein the glycolipid, if present, comprises a compound of formula I ri ocnn / i znz / E / YiAi > R5—O—CH2 c c u σ ü Formula I wherein R1 and R2 are independently hydrogen or a saturated alkyl radical having up to 20 carbon atoms; X is -CH2-, -O- or -NH-; R2 hydrogen or a saturated or unsaturated alkyl radical having up to 20 carbon atoms; R3, R4 and R5 are independently hydrogen, -SO42', -PO42', -CO-Ci-i0 alkyl; R6 is L-alanyl, L-alpha-aminobutyl, L-arginyl, Lasparginyl, L-aspartyl, L-cysteinyl, L-glutamyl, L-glycyl, L-histidyl, L-hydroxyprolyl, L-isoleucyl, Lleucyl, L-lysyl , L-methionyl, L-ornithinyl, L-phenylalanyl, L-prolyl, L-seryl, L-threonyl, L-tyrosyl, L-tryptophanyl and L-valyl or their D-isomers. In the fifth embodiment, the invention provides the adjuvant formulation of the fourth embodiment, wherein the glycolipid is N-(2-deoxy-2-L-leucylamino-b-D-glucopyranos¡l)-Noctadecildodecanoylamide or a salt thereof. In the sixth embodiment, the invention provides the adjuvant formulation of the fifth embodiment, wherein the salt is an acetate. In the seventh embodiment, the invention provides the adjuvant formulation of any one of the first to fourth embodiments, comprising either said monophosphoryl-lipid A (MPL-A) or the analogue thereof and further comprising at least one of a steral and a poly I:C. In the eighth embodiment, the invention provides the adjuvant formulation according to the seventh embodiment, comprising the steral and further comprising a saponin. In the ninth embodiment, the invention provides the adjuvant formulation of any one of the seventh and eighth embodiments, wherein the saponin, if present, is a triterpenoid saponin and the ester, if present, is selected from the group consisting of ergosterol, lanosterol and cholesterol. In the tenth embodiment, the invention provides the adjuvant formulation according to the ninth embodiment, wherein the saponin, if present, is Quil A and the ester, if present, is cholesterol. In the eleventh embodiment, the invention provides the adjuvant formulation according to the seventh embodiment, comprising the poly I:C and further comprising at least one of the quaternary amine and the glycolipid. In the twelfth embodiment, the invention provides the adjuvant formulation of any one of the first-eleventh embodiments, comprising the MPL-A or analog thereof in an amount of 0.5-100 ug per dose. In the thirteenth embodiment, the invention provides the adjuvant formulation according to the twelfth embodiment, wherein the MPL-A or analog thereof is present in an amount of 5-50 ug per dose, or 5-20 ug per dose, or 1-5 ug per dose. In the fourteenth embodiment, the invention provides the adjuvant formulation of any one of the first-thirteenth embodiments, comprising the immunostimulatory oligonucleotide in an amount of 0.5-400 ug per dose. In the fifteenth embodiment, the invention provides the adjuvant formulation of the fourteenth embodiment, wherein the immunostimulatory oligonucleotide is present in an amount of from about 100 to about 250 ug per dose or from about 20 to about 50 ug per dose, or approximately 1 ug per dose. In the sixteenth embodiment, the invention provides the adjuvant formulation of any one of the first through fifteenth embodiments, comprising the polycationic carrier in an amount of between about 0.5 and about 400 mg per dose. In the seventeenth embodiment, the invention provides the adjuvant formulation of the sixteenth embodiment, wherein said polycationic carrier is present in an amount of 50-300 mg per dose or 1-25 mg per dose, or 1-10 mg per dose. dose. In the eighteenth embodiment, the invention provides the adjuvant formulation of any one of the first through seventeenth embodiments, comprising the glycolipid in an amount of between about 0.5 and about 2000 mg per dose. In the 19th modality, the invention provides the 18th modality adjuvant formulation, wherein the glycolipid is present in an amount of about 1000 ug per dose, or 25-50 ug per dose, or 1-10 ug per dose. . In the twentieth embodiment, the invention provides the adjuvant formulation of any one of the first through nineteenth embodiments, comprising the sterol in an amount of between about 0.1 and about 1000 mg per dose. In the twenty-first embodiment, the invention provides the adjuvant formulation of the twentieth embodiment, wherein the sterol is present in an amount of 250-500 ug per dose, or 20-50 ug per dose, or 1-10 ug per dose. In the twenty-second embodiment, the invention provides the adjuvant formulation of any one of the first to twenty-first embodiments, comprising the saponin in an amount between 0.1 and 1000 mg per dose. In the twenty-third embodiment, the invention provides the formulation Al QCnn / l 7Α7 / Β / ΥΙΛΙ adjuvant of the twenty-second modality, wherein the saponin is present in an amount of 250-500 ug per dose, or 20-50 ug per dose, or 1-10 ug per dose. In the twenty-fourth embodiment, the invention provides the adjuvant formulation of any one of the first through twenty-third embodiments, comprising the poly I:C in an amount of between about 0.5 and about 100 ug per dose. In the twenty-fifth embodiment, the invention provides the twenty-fourth embodiment adjuvant formulation, wherein the poly I:C is present in an amount of 5-50 ug per dose, or 5-20 ug per dose, or 1- 5ug per dose. In the twenty-sixth embodiment, the invention provides the adjuvant formulation of any one of the first to twenty-fifth embodiments, comprising the aluminum source, which is an aluminum hydroxide gel. In the twenty-seventh embodiment, the invention provides the adjuvant formulation of the twenty-sixth embodiment, wherein said source of aluminum is present in an amount of 5%-20% v / v of the formulation. In the twenty-eighth embodiment, the invention provides the adjuvant formulation of the twenty-seventh embodiment, wherein said aluminum source is present in an amount of 10% v / v of the formulation. In the twenty-ninth embodiment, the invention provides the adjuvant formulation of any one of claims one to twenty-eighth, wherein the oil phase comprises an oil and an oil-soluble emulsifier. In the thirty-ninth embodiment, the invention provides the adjuvant formulation of any one of the first to twenty-ninth embodiments, wherein said oil phase is present in an amount up to 85% v / v. In the thirty-first embodiment, the invention provides the adjuvant formulation according to the thirty-first embodiment, wherein said oil phase is present in an amount of 51%. In the thirty-second embodiment, the invention provides the adjuvant formulation of any one of the twenty-ninth to thirty-first embodiments, wherein the oil comprises 40-84% v / v of the formulation and the oil-soluble emulsifier comprises the 1-11% v / v of the formulation. In the thirty-third embodiment, the invention provides the adjuvant formulation of the thirty-second embodiment, wherein the oil comprises 45% v / v of the formulation and the oil-soluble emulsifier comprises 6% v / v of the formulation. In the thirty-fourth embodiment, the invention provides the adjuvant formulation according to any one of the first to thirty-third embodiments, wherein said ai ocnn / i ζηζ / Ε / γίΛΐ oil is selected from the group consisting of squalene, vegetable oils, triglycerides , non-metabolizable straight chain alkane oils and any combination thereof. In the thirty-fifth embodiment, the invention provides the adjuvant formulation according to the thirty-fourth embodiment, wherein said oil is a light mineral oil. In the thirty-sixth embodiment, the invention provides a vaccine composition comprising an effective amount of an antigen and the adjuvant formulation according to any one of the first to thirty-fifth embodiments, wherein the oil phase of the composition is at least 50 %v / v. In the thirty-seventh embodiment, the invention provides a vaccine composition comprising an effective amount of an antigen and an adjuvant formulation comprising an oil phase and an aqueous phase, wherein the oil phase comprises at least 50% of the formulation. v / v, a polycationic vehicle and a) a combination of a saponin and a steral and, optionally, a quaternary amine, with the proviso that if said adjuvant formulation consists essentially of DEAE-dextran, Quil A, cholesterol and DDA, the antigen is not E. coli J-5; either b) an immunostimulatory oligonucleotide, provided that if said adjuvant formulation consists essentially of DEAE-dextran and the immunostimulatory oligonucleotide, the antigen comprises or is derived from a pathogen affecting cattle, sheep, horses or pigs and is not it is E. coli J-5 bacterin. In the thirty-eighth embodiment, the invention provides the vaccine composition according to the thirty-seventh embodiment, wherein the saponin, if present, is a triterpenoid saponin, the ester, if present, is selected from the group consisting of ergosterol, lanosterol and cholesterol, the polycationic carrier, if present, is selected from the group consisting of dextran, DEAE-dextran (and derivatives thereof), PEG, guar gums, chitosan derivatives, polycellulose derivatives such as hydroxyethylcellulose (HEC), polyethyleneimene , polyaminos and the quaternary amine, if present, is selected from the group consisting of DDA and avridine. In the thirty-ninth embodiment, the invention provides the vaccine composition according to the thirty-eighth embodiment, wherein the saponin is Quil A, the ester is cholesterol, the polycation carrier is DEAE-dextran, and the quaternary amine is DDA. In the fortieth embodiment, the invention provides the vaccine composition of any one of the thirty-seventh to thirty-ninth embodiments, wherein the immunostimulatory oligonucleotide is a CpG. In the forty-first embodiment, the invention provides the vaccine composition of any one of the thirty-seventh to forty-first embodiments, wherein said Al QCnn / l 7Α7 / Β / ΥΙΛΙ polycationic vehicle is present in an amount between about 0.5 and about 400 mg per dose. In the forty-second embodiment, the invention provides the forty-first embodiment vaccine composition, wherein said polycationic carrier is present in an amount of 50-300 mg per dose or 1-25 mg per dose, or 1-10 mg per dose. In the forty-third embodiment, the invention provides the vaccine composition of any one of the thirty-seventh to forty-second embodiments, comprising the saponin in an amount of between about 0.1 and about 1000 ug per dose. In the forty-fourth embodiment, the invention provides the forty-third embodiment vaccine composition, wherein the saponin is present in an amount of 250-500 ug per dose, or 20-50 ug per dose, or 1-10 ug per dose. In the forty-fifth embodiment, the invention provides the vaccine composition of any one of the thirty-seventh to forty-fourth embodiments, comprising the steral in an amount of between about 0.1 and about 1000 ug per dose. In the forty-sixth embodiment, the invention provides the forty-fifth embodiment vaccine composition, wherein the steral is present in an amount of 250-500 ug per dose, or 20-50 ug per dose, or 1-10 ug per dose. In the forty-seventh embodiment, the invention provides the vaccine composition of any one of the thirty-seventh to forty-sixth embodiments, comprising the quaternary amine in an amount of between about 1 and about 200 ug per dose. In the forty-eighth embodiment, the invention provides the forty-seventh embodiment vaccine composition, wherein the quaternary amine is present in an amount of about 100 ug per dose or between about 10 and about 100 ug per dose or about 5 ug per dose. In the forty-ninth embodiment, the invention provides the vaccine composition of any one of the thirty-seventh to forty-eighth modalities, comprising the immunostimulatory oligonucleotide in an amount of between about 0.5 ug and about 400 ug per dose. In the fiftieth embodiment, the invention provides the forty-ninth embodiment vaccine composition, wherein the immunostimulatory oligonucleotide is present in an amount of 100-250 ug per dose, or 20-50 ug per dose, or about 1 ug per dose. . In the fifty-first embodiment, the invention provides the ai acnn / i znz / R / YiAi vaccine composition of any one of claims thirty-seven to fifty, wherein the oil phase comprises an oil and an oil-soluble emulsifier. In the fifty-second embodiment, the invention provides the vaccine composition of any one of the thirty-seventh to fifty-first embodiments, wherein said oil phase is present in an amount up to 85% v / v. In the fifty-third embodiment, the invention provides the fifty-second embodiment vaccine composition, wherein said oil phase is present in an amount of 51% v / v. In the fifty-fourth embodiment, the invention provides the vaccine composition of any one of the fifty-first to fifty-third embodiments, wherein the oil comprises 40-84% v / v of the vaccine composition and the oil-soluble emulsifier. comprises 1-11% v / v of the vaccine composition. In the fifty-fifth embodiment, the invention provides the vaccine composition of the fifty-third embodiment, wherein the oil comprises 45% v / v of the formulation and the oil-soluble emulsifier comprises 6% v / v of the formulation. . In the fifty-sixth embodiment, the invention provides a vaccine composition comprising an Eimeria maxima and / or C / ostridium perfringens antigen and an adjuvant formulation comprising: a) an oily phase, said oily phase being present in an amount of at least 50% v / v of the composition, a polycationic carrier and, optionally, an immunostimulatory oligonucleotide; either b) an oily phase, said oily phase being present in an amount of at least 50% v / v of the composition, an immunostimulatory oligonucleotide, a sterol and monophosphoryl-lipid A (MPL-A) or an analogue thereof. In the fifty-seventh modality, the invention provides the fifty-sixth modality vaccine composition, comprising antigens against Eimeria maxima and Clostridium perfringens. In the fifty-eighth embodiment, the invention provides the vaccine composition of the fifty-sixth embodiment or the fifty-seventh embodiment claim, wherein said polycationic carrier is DEAE-dextran. In the fifty-ninth embodiment, the invention provides the use of the vaccine composition as claimed in the fifty-sixth to fifty-eighth embodiments for the treatment or prevention of infections caused by Eimeria maxima or Clostridium perfringenense in poultry. In the sixtieth embodiment, the invention provides a vaccine composition Al QCnn / l 7Α7 / Β / ΥΙΛΙ comprising a Neospora antigen and an adjuvant formulation comprising an oil phase, said oil phase being present in an amount of at least 50% v / v of the composition; and a) monophosphoryl-lipid A (MPL-A) or an analogue thereof; either b) a combination of an immunostimulatory oligonucleotide and a polycationic carrier. In the sixty-first embodiment, the invention provides the sixty-first embodiment vaccine composition, comprising the combination of the immunostimulatory oligonucleotide and DEAE-dextran. In the sixty-second embodiment, the invention provides the vaccine composition of the sixtieth embodiment, comprising mnophosphoryl-lipid A (MPL-A) or the analogue thereof, and further comprising the immunostimulatory oligonucleotide. In the sixty-third modality, the invention provides the sixty-second modality vaccine, further comprising steral. In the sixty-fourth embodiment, the invention provides the sixty-third embodiment vaccine, in which the ester is cholesterol. In the sixty-fifth embodiment, the invention provides the vaccine according to any one of the sixty-fifth embodiments, wherein the Neospora antigen is a Neospora caninum antigen. In the sixty-sixth embodiment, the invention provides the use of the vaccine according to any one of the sixty-sixth to sixty-fifth embodiments for the treatment or prevention of an infection caused by Neospora. In the sixty-seventh embodiment, the invention provides a vaccine composition comprising a Chlamydophila abortis antigen and an adjuvant formulation comprising an oil phase, said oil phase being present in an amount of at least 50% v / v of the composition. , a steral, an immunostimulatory oligonucleotide, monophosphoryl-lipid A (MPL-A) or an analog thereof, and poly I:C. In the sixty-eighth embodiment, the invention provides the use of the vaccine according to the sixty-seventh embodiment for the treatment or prevention of abortion caused by C. abortis in sheep. In the sixty-ninth embodiment, the invention provides a vaccine composition comprising myostatin and an adjuvant formulation, said adjuvant formulation comprising an oil phase, said oil phase being present in an amount of at least 50% v / v of the composition, an immunostimulatory oligonucleotide and any of: a) a polycationic vehicle or ri ocnn / i ζηζ / Ε / γίΛΐ b) MPL-A or an analog thereof. In the seventieth modality, the invention provides the sixty-ninth modality vaccine composition comprising MPL-A or the analog thereof, said formulation containing less than 0.5 ug of a steral per 50 ul of said composition. In the seventy-first embodiment, the invention provides the seventy-first embodiment vaccine composition, which does not contain steral. In the seventy-second embodiment, the invention provides the seventy-second embodiment vaccine composition, wherein the ester is cholesterol. In the seventy-third embodiment, the invention provides the use of the vaccine according to any one of the embodiments 69 to 72 to reduce the amount of myostatin in an animal. In the seventy-fourth embodiment, the invention provides use according to the seventy-third embodiment, wherein said animal is a poultry animal. In the seventy-fifth embodiment, the invention provides a vaccine composition comprising a Trueperella pyogenes antigen and an adjuvant formulation, the adjuvant formulation comprising an oil phase, said oil phase being present in an amount of at least 50% v / v of the composition, an immunostimulatory oligonucleotide and a polycationic vehicle. In the seventy-sixth embodiment, the invention provides the seventy-fifth embodiment vaccine composition, wherein the Trueperella pyogenes antigen is pyolysin. In the seventy-seventh mode, the invention provides the use of the vaccine composition of the seventy-fourth or seventy-fifth modes for the treatment or prevention of an infection caused by Trueperella pyogenes. In the seventy-eighth embodiment, the invention provides a vaccine composition comprising an E coli antigen, a BRV antigen or a BCV antigen and an adjuvant formulation, wherein said adjuvant formulation comprises an oil phase present in an amount of at least 50% v / v of said vaccine composition, an immunostimulatory oligonucleotide and at least one of a polycationic carrier and a source of aluminum. In the seventy-ninth embodiment, the invention provides the seventy-eighth embodiment vaccine composition, comprising E coti antigen, a BRV antigen, and a BCV antigen. In the eightieth embodiment, the invention provides the seventy-eighth or seventy-ninth embodiment vaccine composition wherein Al QCnn / l 7Α7 / Β / ΥΙΛΙ a) the E coH antigen, if present, is selected from the group consisting of K99 from Ecali, F41 from Eco / i and a combination thereof; b) the BRV antigen, if present, is selected from the group consisting of BRV G6, BRV G10 and a combination thereof. In the eighty-first embodiment, the invention provides the vaccine composition according to any one of the seventy-eighth to eightieth embodiments, wherein the polycationic carrier, if present, is DEAE-dextran and the immunostimulatory oligonucleotide is a CpG. In the eighty-second embodiment, the invention provides the vaccine composition according to any one of the seventy-eighth to eighty-first embodiments, comprising the aluminum source, which is an aluminum hydroxide gel. In the eighty-third embodiment, the invention provides the eighty-second embodiment vaccine composition, wherein said source of aluminum is present in an amount of 5%-20% v / v. In the eighty-fourth embodiment, the invention provides the eighty-third embodiment vaccine composition, wherein said source of aluminum is present in an amount of 10%-17% v / v. In the eighty-fifth embodiment, the invention provides the use of the vaccine composition according to any one of the seventy-eighth to eighty-fourth embodiments for the treatment or prevention of enteritis caused by E coli, BCV or BRV in a bovine animal. In the eighty-sixth embodiment, the invention provides use according to the ninety-first embodiment, wherein said vaccine causes at least six-month immunity to said antigen(s). In the eighty-seventh embodiment, the invention provides a vaccine composition comprising a Rhipicephalus microplus antigen and an adjuvant, said adjuvant being selected from the group consisting of: a) an aqueous adjuvant comprising an immunostimulatory oligonucleotide, a saponin, a ester, a quaternary amine, a polyacrylic polymer and a glycolipid and b) an oil-based adjuvant comprising an oily phase present in an amount of at least 50% v / v of the vaccine composition and comprising an immunostimulatory oligonucleotide and a polycationic carrier. In the eighty-eighth embodiment, the invention provides the seventy-seventh embodiment vaccine composition, wherein the saponin is Quil A, the steral is ai acnn / i znz / E / YiAi cholesterol, the quaternary amine is DDA, the glycolipid is N-(2-deoxy-2-L-leucylamino-b-Dglucopyranosyl)-N-octadecyldodecanolamide or a salt thereof and the immunostimulatory oligonucleotide is a CpG. In the eighty-ninth embodiment, the invention provides the eighty-seventh embodiment vaccine composition, wherein the polycationic carrier is DEAE-dextran and the immunostimulatory oligonucleotide is a CpG. In the ninetieth embodiment, the invention provides the vaccine composition of any one of the eighty-seventh to eighty-ninth embodiments, wherein the Rhipicepha / us microp / us antigen is the Bm86 protein. In the ninety-first embodiment, the invention provides the use of the vaccine composition according to any one of the eighty-seventh to the ninetieth embodiments for the treatment or prevention of an infection caused by Rhipicepha / us microp / us. In the ninety-second embodiment, the invention provides a vaccine composition comprising a foot-and-mouth disease (FMD) antigen and an adjuvant formulation, said adjuvant formulation comprising an oil phase present in an amount of at least 36% v / v of said vaccine composition, an immunostimulatory oligonucleotide and a polycationic carrier, wherein said vaccine composition is a water-in-oil emulsion. In different embodiments, said FMDV antigen may be either wild-type FMDV, genetically modified and / or attenuated FMDV strains, or recombinantly expressed FMDV structural proteins such as FMDV virus-like particles (VLPs). serotypes A, C, O, Asian, SAT1, SAT2, or SAT3. In the ninety-third embodiment, the invention provides the ninety-second embodiment vaccine composition, wherein the immunostimulatory oligonucleotide is a CpG and the polycationic carrier is DEAE-dextran. In the ninety-fourth embodiment, the invention provides the vaccine composition of the ninety-second or ninety-third embodiment, wherein the antigen is, the invention provides the vaccine composition as claimed in the ninety-eighth or ninety-ninth embodiment, in the that the antigen is derived from a genetically modified FMD-LL3B3D platform virus that is attenuated in cattle and pigs, specifically FMDLL3B3D-A24 Cruzeiro. In the ninety-fifth embodiment, the invention provides the use of the vaccine composition of either the ninety-second or ninety-fourth embodiment for the treatment or prevention of FMD in cattle. In the ninety-sixth embodiment, the invention provides a vaccine composition comprising a Streptococcus uberis (S. uberis) antigen and a formulation Ei ocnn / i znz / E / YiAi adjuvant comprising an oily phase, said oily phase being present in an amount of at least 50% v / v of the composition, and a polycationic vehicle; and a) an immunostimulatory oligonucleotide, b) a combination comprising a saponin, a ester and a quaternary amine, or c) a combination thereof. In the ninety-seventh embodiment, the invention provides a ninety-seventh embodiment vaccine composition, wherein the antigen is a Suberis adhesion molecule or an immunogenic fragment thereof. In the ninety-eighth embodiment, the invention provides the use of the vaccine according to either one of the ninety-sixth or ninety-seventh embodiments for the treatment or prevention of an infection caused by Suberis. The following examples are presented as illustrative embodiments, but should not be construed as limiting the scope of the invention. Many changes, variations, modifications, and other uses and applications of the present invention will be apparent to those skilled in the art. EXAMPLES EXAMPLE 1· Development of a recombinant vaccination strategy to enhance immunity against necrotic enteritis. The aim of the study was to evaluate the effects of an in vivo vaccination with adjuvanted recombinant clostridial vaccine against infection for the in vivo challenge with Eimeria maximay C / ostridium perfringenense in the pathological model of necrotic enteritis. materials and procedures Recombinant proteins: Full-length coding sequences of genes encoding C. perfringens (ATCC 13124, American Type Culture Collection, Manassas, VA) NetB and EF-Tu were cloned by PCR into the pET32a(+) vector with a polyhistidine NH2 epitope tag -terminal. The cloned genes were transformed into coiicompetent Escherichia, the bacteria were cultured for 16 h at 37 °C and induced for 5 h at 37 °C with 1.0 mM isopropyl-p-D-thiogalactopyranoside. Rl ocnn / l 7Π7 / Β / ΥΙΛΙ (Amresco, Cleveland, OH). Bacteria were collected by centrifugation at 10,000 rpm for 10 min at 4oC, resuspended in PBS, disrupted by sonication, and centrifuged at 10,000 rpm for 15 min. The supernatant was incubated for 1 h at 22 °C with NiNTA agarose (Qiagen, Valencia, CA), the resin was washed with PBS, and purified clostridial proteins were eluted with 250 mM imidazole in PBS, pH 9.2. Protein purity was confirmed on Coomassie blue stained SDS-acrylamide gels. Protein concentration was determined using a commercial kit from Sigma. Animals: Broiler birds (Ross / Ross) obtained from Longeneckers Hatchery (Elizabethtown, PA) were transported to BARC-East, Building 1082 and chicks were housed in Petersime starter units according to guidelines established by the Committee on the Care of Small Animals. (Small Animal Care Committee) of BARC. Birds were kept in rearing cages in a facility free of Eimeria and transferred to large hanging cages in a separate location where they were infected and maintained until the end of the experimental period for study of challenge infection with live pathogens. . All procedures regarding transport, body weight measurement, infection, and blood and spleen collection were approved by the BARC Small Animal Care Committee (joined with SOP). The ARS BARC Small Animal Care Committee has established guidelines for animal experiments at BARC and conducts regular inspection of all animal facilities. Immunization: Primary immunization was performed by subcutaneous injection of one-day-old broiler chickens with 100 ul of vaccine (Ag 100 ug / dose). Secondary immunization was performed by subcutaneous injection of broiler chickens of the same days of age with 100 ul of vaccine (Ag 100 ug / dose). Taunt with Eimeria: BARC strains of Eimeria spp. which were maintained in the Animal Parasitic Diseases Laboratory and propagated according to the established procedure. E. maxima (41A) was cleaned by flotation in 5% sodium hypodorite, washed three times with PBS and viability was assessed by trypan blue using a hemocytometer. The number of oocysts is based solely on the sporulated oocysts. Six days after the booster immunization, the chickens were inoculated into the esophagus with 10,000 E. maxima using an inoculation needle. Al QCnn / l 7Α7 / Β / ΥΙΛΙ Challenge with C. perfringens. Four days after infection with Eimeria, birds in NE (necrotic enteritis) groups were inoculated into the esophagus with 1 χ 109 CFU of Clostridium perfringens using one inoculation needle each time. Analysis: Birds were weighed on the day of arrival, just before EM challenge, before C. perfringens challenge, 2 days after C.P. and 10 days after challenge with C.P. to calculate the weight gained. To score intestinal lesions, birds (5 birds / group) were euthanized two days after C.P. Intestinal segments of approximately 20 cm extending 10 cm before and after the diverticulum were obtained and cut longitudinally. Injury scores were assigned by 2 independent observers from 0 to 4 in ascending order of injury severity. Two major C perfringens virulence factors in chickens are alphatoxin and NetB toxin (necrotic enteritis B-like), both of which are implicated in the pathogenesis of NE. Additional C. perfringens proteins that may be involved in bacterial pathogenesis and protective host immunity including pyruvate:ferredoxin oxidoreductase (PFO) and elongation factor G (EF-G) were previously reported to induce protective immunity against challenge infection. experimental with C. perfringens. Accordingly, antibody titers to these factors were determined as described below. Five birds per group were randomly selected for blood collection, which was collected by cardiac puncture immediately after euthanasia. Sera were obtained by low speed centrifugation and an enzyme-linked immunosorbent assay (ELISA) was used to measure antibody levels. specific for a-toxin, NetB, EF and PFO. Briefly, 96-well microtiter plates were coated overnight with 1.0 pg / well of recombinant α-toxin, NetB, EF and PFO proteins. Plates were washed with PBS containing 0.05% Tween (PBS-T) and blocked with PBS containing 1% BSA. Sera (100 μΙ / well) were incubated for 2 h at room temperature with gentle shaking. Plates were washed with PBS-T and bound antibody was detected with peroxidase-conjugated rabbit anti-chicken IgG (Sigma, St. Louis, MO) and peroxidase-specific substrate. Optical density (OD) at 450 nm was measured with an automated microplate reader (Bio-Rad, Richmond, CA). Statistical analysis: All values are expressed as mean ± SEM. Mean values for body weight gain and injury score were compared between groups by Turkey's test following an ANOVA using SPSS 15.0 for Windows (SPSS Inc., ri ocnn / i znz / E / YiAi Chicago, IL). Differences between means were considered significant at p < 0.05. The experimental design is illustrated in Table 1. TABLE 1. 5 Bird group number (Number) Protein (100 pg / bird) Adjuvant NE infection (EM+CP)* 1 15 - 10 mM pH buffer solution of - 10 2 15 - 10 mM pH buffer solution of + 3 15 NetB (50 pg) EF-Tu (50 pg) pH buffer 10 mM de + 4 15 Π TXO + 15 5 15 TCMO + 6 15 » XO + 7 15 !! XOM + 8 15 Π SP-OIL + 20 9 15 1! 5% AMPHIGEN® + 10 15 5% AMPHIGEN® poly I:C + + 5% AMPHIGEN® + 25 11 15 CpG + 5% AMPHIGEN® + 12 15 DEAE-dextran + 5% AMPHIGEN® + 30 13 15 DAD + *Chickens were infected orally with 1.0 χ 104 oocysts / bird of E. maxima (EM) on day 14 after hatching and with 1.0 χ 109 CFU / bird of C. perfringens (CP) on day 18. The compositions of the adjuvants were the following (per 50 ul): TXO: SEQ ID NO: 8 was present in an amount of 1 ug, DEAE-dextran was present in an amount of 5 ug, light mineral oil was present in an amount of 51% v / v of the composition TCMO: SEQ ID NO: 8 was present in a 1 ug amount, cholesterol was present in a 1 ug amount, MPL-A was present in a 1 ug / 50 ul dose amount, light mineral oil was present in an amount of 51% v / v of the composition XO: DEAE-dextran was present in an amount of 5 ug, light mineral oil was present in an amount of 51% v / v of the composition. XOM: DEAE-dextran was present in an amount of 5 ug, light mineral oil was present in an amount of 51% v / v of the composition, MPL-A was present in an amount of 1 ug. 5% AMPHIGEN® + poly I:C: Poly I:C was present in an amount of 1 ug. 5% AMPHIGEN® -ι-CpG: SEQ ID NO: was present in an amount of 1 ug. 5% AMPHIGEN® + DEAE-dextran: The DEAE-dextran was present in an amount of 25 ug. 5% AMPHIGEN® + DDA: DDA was present in an amount of 1 ug. Body weight gain was significantly reduced with MS and CP infection in the NE control group (P < 0.05). However, overall body weight gain was increased in the groups immunized with recombinant CP proteins (Net B + EF) by 4~21%. The significant difference from the NE control was found in the Prot TCMO group that was immunized with TCMO adjuvant-conjugated CP proteins. TABLE 2: Body weight gain ai acnn / i znz / E / YiAi Treatment Group Mean SEM 1 Cont 347.93 9.387 2 Cont NE 286.36 14.436 3 Prot 317.86 7.828 ri ocnn / i znz / E / YiAi (continued) Group Treatment Mean SEM 4 TXO Prot 316.42 8.826 5 TCMO Prot 345.73 11.745 6 XO Prot 334.67 8.605 7 XOM Prot 331.17 11.387 8 SPO Prot 304.09 10.330 9 AMP Prot 310.09 9.4 79 10 Prot AMPPIC 314.86 9,571 11 Prot AMP CPG 313.82 11,976 12 Prot AMP DEAE 299.20 15,000 13 Prot AMP DDA 301.25 10,440 TABLE 3. injury score Group Mean SEM 2 Cont NE 3.0 0.0 3 Prot 2.7 0.2 4 Prot TXO 2.5 0.2 5 Prot TCMO 2.6 0.2 6 Prot XO 1.7 0.2 7 Prot XOM 2.4 0.2 8 Prot SPO 2.4 0.2 9 Prot AMP 1.7 0.1 10 Prot AMPP CI 2.1 0.1 11 Prot AMP CPG 2.3 0.2 12 Prot AMP DEAE 2.1 0.1 13 Prot AMP DDA 2.2 0.2 Six days after EM infection and 2 days after CP infection, antibody responses against α-toxin, Net-B, EF and PFO were assessed. The results are provided in Table 4. Briefly, CP protein generally increases antibody titers against CP antigens in birds immunized with CP proteins. Ab responses to Net B, EF and PFO antigens were much higher than to α-toxin. ri acnn / i znz / R / YiAi TABLE 4. Ab responses to Net B, EF, and PFO antigens c Groups a-toxin Net B Mean SEM EF Mean SEM PFO Mean SEM Mean SEM 2 NE cont 0.36 0.02 0.33 0.01 0.21 0.01 0.22 0.01 3 Prot 0.40 0.04 0.44 0.05 0.40 0.09 0.36 0.05 4 Prot TXO 0.39 0.03 0.41 0.04 0.56 0.05 0.40 0.03 5 Prot TCMO 0.34 0.02 0.42 0.03 0.48 0.06 0.40 0.06 1C 6 Prot XO 0.34 0.02 0.53 0.05 0.38 0.07 0.36 0.04 7 Prot XOM 0.33 0.02 0.40 0.04 0 .55 0.03 0.41 0.04 8 Prot SPO 0.30 0.01 0.33 0.02 0.19 0.02 0.20 0.02 9 Prot AMP 0.37 0.01 0.33 0.00 0.22 0.03 0.32 0.07 10 AMPPIC Prot 0.32 0.02 0.53 0.06 0.36 0.10 0.33 0.02 1E 11 AMP CPG Prot 0.42 0.02 0.41 0.02 0.24 0.08 0.28 0.01 12 Prot AMP DEAE0.38 0.02 0.53 0.05 0.17 0.02 0.23 0.03 13 Prot AMP DDA 0.41 0.01 0.58 0.02 0.45 0.03 0.36 0.03 EXAMPLE 2: Antimyostatin vaccine in chickens. Myostatin is a secreted growth differentiation factor that is a member of the TGF beta family of proteins that inhibits muscle differentiation and growth. Myostatin is produced primarily in skeletal muscle cells, circulates in the blood, and acts on muscle tissue by binding to a cell-bound receptor called the type II fortune teller receptor. Consequently, myostatin inhibition results in animals having an increased amount of meat / muscle. One approach to reducing the amount of myostatin in an animal is to generate an anti-myostatin immune response, which can be conveniently measured by anti-myostatin antibody titers. In this example a chicken model is used. Cobb 500 Parent Stock and Ross 308 hens (12 to 10 weeks of age, respectively) were challenged with a vaccine containing myostatin-conjugated peptide and adjuvant formulation. The adjuvant formulations used in the study are shown in Table 5. TABLE 5. treatment groups. Adjuvant Treatment Vehicle Dose T01 CFA / IFA CRM 50 ug T02 IFA / CFA CRM 50 ug T03 CFA / IFA KLH / CRM 50 ug T04 TCMO KLH / CRM 50 ug T05 TCMO CRM 200 ug / 50 ug T06 TMO CRM 200 ug / 50 ug T07 TCMO CRM 50 ug T08 MO CRM 50 ug T09 TMO CRM 50 ug TIO TXO CRM 50 ug The designation 200 ug / 50 ug refers to the amount of antigen in priming / boosting dose, volume 0.2 ml. The components of the adjuvants are described in Table 6. Cobb 500 Parent Stock and Ross 308 hens were primed at week 12 or 10 and boosted at week 18. Serum titers of anti-myostatin antibodies were measured by ELISA prior to vaccination and every two weeks after challenge until 22 and 20 weeks of age, respectively. Groups T06, T07, T09 and TIO produced the highest responses (geometric mean antibody titers between 50,000 and 15,000 at week 22). Among these four groups, Cobb 500 birds from groups T06 and T07 showed geometric mean scores greater than 100,000. Al QCnn / l 7Π7 / Β / ΥΙΛΙ TABLE 6. Adjuvant Name of Adjuvant Component of Adjuvant Concentration / Dose TCMO SEQ ID N°: 8 / cholesterol / MPLA / oil 10 ug / 10 ug / 5 ug / oil Drakeol 5 (45%), SPAN® 80(6.3%) and TWEEN ® 80 (1.45%) MO (20:80 W:O) MPLA low viscosity emulsion (20:80 W:O) MPLA- 5 ug / mineral oil Drakeol 6, SPAN and TWEEN 80 TMO (20:80 W: O) Use of MO emulsion and mixture of CpG and conjugated peptides SEQ ID N°: 8 / low viscosity emulsion of MPLA (20:80 W:O) 10 ug / 5 ug / mineral oil Drakeol 6, SPAN and TWEEN 80 TXO SEQ ID N°: 8 / DEAEDextran 10 ug / 20 ug / mineral oil Drakeol 5 (45%), SPAN® 80 (6.3%) and TWEEN® 80 (1.45%) EXAMPLE 3, Vaccines against T. pyogenes Truepurella pyogenes (formerly Arcanobacterium pyogenes, and formerly Actinomyces pyogenes and also Corynebacterium pyogenes) often causes severe clinical metritis in cattle characterized by a thick purulent discharge. The malodour sometimes associated with this condition is probably caused by anaerobic bacteria that are also present but not detected by routine culture procedures. The disease is most common in dry cows and calves before or at calving, and occasionally occurs in lactating animals as a sequel to a lesion of the teat or udder. Economically important diseases caused by this organism include metritis and abortion in dairy cows and liver abscesses in feeder cattle. Pyolysin (PLO), a cholesterol-dependent cytolysin expressed by Truepurella pyogenes, is an important host protective antigen. Angus crossbred beef cattle approximately 14 months of age were used in this study. The animals were in good general health and did not have any complicating diseases at the time of their inclusion in the study. The animals had free access to food and water. Formulations: All bacteria (E coli and T pyogenes) at 1 X 109 per dose. Pyolysin was administered at 150 micrograms per dose to animals in groups T02-T07. The T01 group was used as a control. The adjuvant formulations analyzed in this study were the following: ISC / Poli IC - ISC 1000 pg / Poly I:C 50 pg at a dose of 2 ml ISC / CpG - ISC 1000 pg / 100 pg CpG (SEQ ID NO: 8 ) in a dose of 2 ml TXO - CpG 100 pg (SEQ ID NO: 8) / DEAE-dextran / mineral oil 5LT NF in a dose of 2 ml QCDCRT- Quil A 150 pg / cholesterol 150 pg / DDA 100 pg / CARBOPOL® (polyacrylic polymer) 0.0375% / R1005 1000 pg / CpG (SEQ ID NO: 8) 100 pg in a 2 ml dose QAC- Quil A 500 pg / cholesterol 500 pg / AMPHIGEN® (lecithin oil emulsion) 2.5% in a 2 mL dose Pyolysin antibody was measured using an indirect ELISA, antigen on the plate followed by serum sample (primary antibody) followed by anti-bovine IgG conjugate was measured on days 0, 28 and 56. All samples and controls were diluted 1:2000 and the response was determined by calculating the ratio of the OD of the sample to the OD of the positive control (Pos Ctrl was pooled serum from convalescent animals). Antibody was detected by HRP-conjugated sheep anti-bovine IgG. TABLE 7: Study design Treatment group Number of animals Treatment* Day Dose Dose units Route+ Uterine challenge T01 8 Saline solution 0.28 2 ml SC, SC Day 56 5x108 T02 8 E. col i + T (A). piogenes + PLO in ISC / Poli:IC 0.28 2 mi IN, SC Day 56 5x108 T03 8 E. coi i + T (A). piogenes + PLO in ISC / CpG 0.28 2 mi IN, SC Day 56 5x108 T04 8 E. coi i + T (A), piogenes + PLO in TXO 0.28 2 mi SC, SC Day 56 5x108 T05 8 E. coi i + T (A), pyogenes + PLO in QCDCRT 0, 28 2 mi IN, SC Day 56 5x108 T06 8 E. coi i + T (A), pyogenes + PLO in QAC 0, 28 2 mi SC, SC Day 56 5x108 T07 8 PLO in ISC / Poly :IC 0.28 2 ml IN, SC Day 56 5x108 * E. coti strain 51323 + T(A). Depa de piogenes 51496, PLO=pius + SC= subcutaneous, IN= intranasal. isine The results are shown in table 8. ai ocnn / i ζπζ / β / υιλι TABLE 8 MMC from IgG to PLO (The time point is the study day) Treatment No. Day 00 Day 28 Day 56 T01 0.216 0.226 0.208 T02 0.274 0.245 0.444 T03 0.252 0.229 0.451 T04 0.205 0.506* 0.590* T0 5 0.291 0.246 0.373 T06 0.243 0.512* 0.687* T07 0.315 0.280 0.624 Groups T04 and T06 (adjuvant TXO and QAC) responded significantly better than control (P<0.05). In addition, multiple trends were found between different treatment groups (selected as differences those where P<0.1). These trends are summarized in Table 9. TABLE 9. Differences between groups on days 0 (first parameter), 28 (second parameter), 56 (third parameter). Y indicates that P < 0.1. T01 T02 T03 T04 T05 T06 T07 T01 X X X X X X X T02 N, N, S X X X X X X T03 N, N, S N, N, N X X X X X T04 N, S, S S, S, S N, S, N X X X X T05 S, N, S N, N, N N, N, N Y, S, N X X X T06 N, Y, Y N, S, Y N, S, Y N, N, Y N, S, Y X X T07 Y, N, Y N, N, Y N, N, N Y, Y, N N, N, N Y, Y, Y X EXAMPLE 4. Evaluation of pyolysin vaccine formulations in lactating dairy cows against challenge of metritis. The objective of this study was to evaluate the efficacy of TXO-adjuvanted recombinant and native pyolysin vaccine formulations in non-pregnant lactating Holstein or Holstein-cross dairy cows using an artificial metritis challenge model. Animals were in good general health, had no complicating diseases, and did not receive any chemotherapy, systemic antibiotics, or other anti-inflammatory medication for seven (7) days before and after vaccination and challenge. They were at their Iaa 3 parity, had no prior history of metritis, and were not culture positive for prior challenge with T pyogenes (day -1 or 0). Animals that developed clinically significant early disease during the study were withdrawn. The animals had free access to food for at least 20 hours in each 24-hour period, with the sole exception of being milked. A mixed feed ration of basal feed, representative of the industry for lactation, was used. Animals were acclimatized for at least 7 days prior to the start of the study. Formulated vaccines administered to cows (n=20 per group) contained the following components: T01Saline solution; T02- TXO + native pyolysin (nPLO); T03- TXO + recombinant pyolysin (rPLO). Recimbinant pyolysin was obtained by cloning, expression and purification of the Corynebacterium glutamicum antigen. The purified protein was then inactivated by treatment with formalin. Native pyolysin, expressed and purified from Trueperella pyogenes, was also inactivated by formalin treatment. The TXO adjuvant contained CpG oligonucleotides, DEAE-dextran, mineral oil, and the surfactants Span 80 and Tween 80. On the day of vaccination, the appropriate IVP (Table 10) was administered subcutaneously. The vaccine was administered to the neck on day 0 and to the opposite side of the neck on day 28. The vaccine administration site was assessed on study days 0, 1, 2, 3, 7, 28, 29, 30, 31, 35, 49 and 77 to determine injection site reactions. On the day of vaccination, the administration site was assessed to confirm that no swelling was present prior to the administration of the vaccine. On study days 28, 49, and 77, both sides of the neck were observed. Injection site assessments were recorded. Rectal temperature was also measured and recorded on study days 0 (before 1vaccination), 1, 2, 3, 7, 28 (before 2nd vaccination), 29, 30, 31, and 35 during the vaccination phase. Rectal temperature was also measured and recorded on challenge days 0 to 28. Post-vaccination clinical observations were recorded on study days 0, 1, 2, 3, 7, 28, 29, 30, 31, and 35 (during the vaccination phase). In addition, clinical observations were made and recorded during the challenge phase from day 49 to day 77. Antibody responses to pyolysin were determined by ELISA on study days 0, 28, 49 and the last day of the study (d77). A hemolytic inhibition assay was also performed on each serum sample. This assay measures the anti-pyolysin antibody response, which correlates with biological activity (protection). ai acnn / i znz / R / YiAi ri acnn / i znz / R / YiAi TABLE 10, Group No. of animals Treatment Day Route T01 20 Saline solution 0.28 SQ T02 20 TXO + native pyosilin 0.28 SQ T03 20 TXO + recombinant pyosilin 0.28 SQ Before challenge, the ovarian cycle of all cows was synchronized. Progesterone was administered prior to challenge and daily throughout the 28-day challenge phase. Using a sterile cannula similar to a brood cannula, 10 ml of a challenge strain of Escherichia coti and 10 ml of a challenge strain of Trueperella pyogenes were infused (predetermined challenge doses), each in a separate syringe, into the uterus of all cows on challenge day 0. To ensure complete administration of challenge material, the cannula was flushed with 10 mL of sterile culture medium. The challenge was considered successful if at least 60% of the animals in the treatment group T01 (control group) developed metritis. The presence of metritis would be indicated by the presence of a mucopurulent uterine / vaginal discharge with a score > 2. (This scoring system was adopted from the procedure described by Sheldon et al., Theriogenology, 65:1516-1530, 2006; in that scores of 0 and 1 are considered normal). The primary endpoint was the presence of a mucopurulent uterine / vaginal discharge with a score > 2, indicating the presence of metritis. Uterine / vaginal discharge was collected using an aseptic Simcro MetriCheck™ device with an aseptic cup and scored from challenge day 0 to 28 (study day 49 to 77). Treatment was considered effective if only T01 cows developed clinical metritis, or if the duration and / or proportion of days of mucopurulent vaginal discharge (score > 2) were significantly shorter (p= <0.1) compared to controls. If there were no significant differences between groups in duration and proportion of days with metritis, then the frequency of isolation of T pyogenes from uterine bacterial swabs was used as supporting data to determine vaccine efficacy. The safety of the respective vaccines was assessed based on injection site assessments, rectal temperatures, and any adverse effects on lactation. Collected metritis data (present vaginal / uterine discharge, Yes / No; vaginal / uterine discharge score) were summarized for each animal at each time point, and used to determine the frequency distributions of each category for each treatment in each time point. Frequency distributions of whether an animal was normal / abnormal (normal is a score = 0 or 1; abnormal is a score > 2) for each sign of metritis (eg, vaginal / uterine discharge score) were summarized by treatment. and time point. If an animal had an abnormal uterine discharge score (a score > 2) it was summarized by treatment, using a generalized linear mixed model (Proc Glimmix) with a binomial error distribution and a logit link function. The statistical model includes the fixed treatment effect and the random batch effect. Treatment groups were contrasted. This was repeated for each metritis variable described in this paragraph. If the Glimmix Proc did not converge for a metritis variable, then Fisher's exact test was used instead of treatment group comparison. The duration of an abnormal score (for each metritis variable) was determined for each animal and calculated as (last abnormal time point minus first abnormal time point) + 1. The duration of the abnormal score was set to zero for animals that did not they had time points with an abnormal score for that metritis variable. Abnormal score duration was calculated as (last scheduled data collection time point minus first abnormal time point) + 1 for animals that withdrew from the study before the last scheduled data collection time point for that metritis variable. Abnormal score duration (for each metritis variable) was log-transformed and then analyzed with a general linear mixed model with fixed effect: treatment and random effect: residual. Linear combinations of parameter estimates were used in a priori contrast after analysis to determine a significant treatment effect (P < 0.10). Comparisons between treatments were made. The backtransformed least-squares means, their standard errors, and their 90% confidence intervals were calculated for each treatment group from least-squares parameter estimates obtained from the analyses. The proportion of days with an abnormal score (for each metritis variable) as well as the proportion of days with a normal absence of both E. coii and T pyogenes from discharge were determined for each animal (absence is considered a value <=1+). Each was then transformed using the square root arcsine transformation prior to analysis. These transformed proportion of days variables were then analyzed with a general linear mixed model with fixed effect: treatment and random effect: residual. Linear combinations of parameter estimates were used in a priori contrasts after analysis to determine a significant treatment effect (P < 0.10). Comparisons between treatments were made. The backtransformed least-squares means, their standard errors, and their 90% confidence intervals were calculated for each treatment group from least-squares parameter estimates obtained from the analyses. The ai ocnn / i ζηζ / Ε / γίΛΐ frequency distributions of whether an animal had the presence of E. co / i (a value >1+ is considered presence), presence of T pyogenes (a value >1+ is considered presence) and presence of both E. co / i and T pyogenes (a value >1+ is considered presence), were summarized by treatment at each time point. Results. An antibody response to pyolysin was evaluated by ELISA, by measuring serum IgG levels. The results (Table 11), presented as mean least squares (MMC) of valuations, indicate that the valuations were significantly higher in T02 and T03 cows, compared to T01, on study days 28, 49 and 77. They also suggest that there were no significant differences between the evaluations of groups T02 and T03. With respect to titrations of antibodies in utero, also evaluated by ELISA, the results (Table 12) showed that there were significantly higher titrations on days 49 and 77 in T02 and T03 cows, compared to those of T01, on the same days. As for hemolytic inhibitory antibodies, the results in Table 13 indicate that animals from T02 had significantly higher titers on study days 49 and 77 than those from groups T01 and T03. Al QCnn / l 7Α7 / Β / ΥΙΛΙ TABLE 11. Serum IgG titers S:P ratio MMC1 Day 0 Day 28 Day 49 Day 77 T01 0.250 a 0.197 a 0.178 a 0.366 a T02 0.226 a 0.645 b 0.782 b 0.820 b T03 0.224 a 0.626 b 0.725 b 0. 746b 1Different superscripts represent significant differences between groups. TABLE 12. IgG anti-PLO MMC1 in utero Day 49 Day 77 T01 0.033a 0.120a T02 0.433b 0.353b T03 0.444b 0.382b 1Different superscripts represent significant differences between groups. Al QCnn / l 7Π7 / Β / ΥΙΛΙ TABLE 13, Serum Hl antibody S:P ratio MMC1 Day 0 Day 28 Day 49 Day 77 T01 0.09 a 0.10 a 0.11 a 0.12 a T02 0.08 a 0.78 b 2.75 c 1.12 c T03 0.09 a 0.77 b 2.13 b 0.84 b 1Different superscripts represent significant differences between groups. Regarding the main variable evaluated, the level of mucopurulent uterine / vaginal discharge (vaginal discharge score or PDV), when the duration of metritis was measured, was significantly shorter in the T02 group, compared to the T01 and T03 groups. , measured on days 7 and 10 after challenge with the bacteria (Tables 14, 15). TABLE 14. Duration of metritis (PDV > 2); MMC1 Week 1 (days 50 to 56) Challenge day 0 to 10 T01 4.2a 7.1a T02 n-PLO 2.2b 4.2b T03 r-PLO 4.3a'c 7.4a'c 1Different superscripts represent significant differences between groups. Table 15. P values; days l° to 7 P values; days 1 to 10 Treatment differences T01vT02 0.0096 0.0276 YES T01vT03 0.8658 0.6962 No T02 v T03 0.0063 0.0109 YES As for the % of days that metritis was evident (i.e., a PDV > 2) within a 10-day period after challenge (Tables 16 and 17), it is evident that group T02 had abnormal days of fever, compared to groups T01 and T03. It was also shown that T. pyogenes was isolated more frequently from cows of the T03 group (data not shown). Thus, the most prominent vaccine effect was in the T02 (native pyolysin + TXO) group. Rl ocnn / l 7Π7 / Ε / ΥΙΛΙ TABLE 16. % of normal days Week 1 Challenge day 0 to 10 T01 70±6.7% 75±6.1% (25%) T02 44.3±10.4% 53.1±9.7%(46.9%) T03 67.2±6.4% 73.4±5.7% (26.6% ) TABLE 17. P values; days 1 to 7 P values; days 1 to 10 T01v T02 0.0472 0.0594 T01v T03 0.7712 0.8204 T02 v T03 0.0699 0.0790 An additional study was conducted to evaluate the efficacy of experimental metritis vaccines in novel adjuvant formulations in pregnant dairy cows. In this study, pregnant cows were vaccinated during the dry period. Efficacy was measured during the first 10 days after delivery. Pregnant Holstein or Holstein-crossed cows in their Iaa 3 lactation were selected for the study. All selected cows were in good general health, had no prior history of metritis, and had known expected calving data. They did not have any complicating illnesses and did not receive chemotherapy, systemic antibiotics, or other anti-inflammatory medication during the seven (7) days before and after vaccination. Animals that developed clinically significant disease concurrently during the study were withdrawn. During the course of the study, the animals had free access to food for at least 20 hours in each 24-hour period, the only exception being milking. The animals also had free access to water throughout the study. The vaccines administered to the groups (n=15 / group) were as follows: T01 animals received a 2 ml vaccine consisting of saline solution; those in T02 received a 2 mL vaccine consisting of ISCOMS / Poli I:C + nPLO; those in T03 received a 2 mL vaccine consisting of TXO + nPLO; those in T04 received a 2 ml vaccine consisting of TXO + Escherichia coti + Trueperella pyogenes + nPLO. (All vaccine antigens were inactivated with formalin) After arrival, the animals were allowed to acclimatize for 7 days. Approximately 2 months before parturition (Study Day 0), animals received the first vaccination subcutaneously on the left side of the neck, except for animals in group T02, which received the vaccine intranasally (Table 18). Twenty-eight days later, all animals received the second vaccination subcutaneously in the right side of the neck (Table 18). Started with the first vaccination, all the cows dried up. ai ocnn / i ζηζ / Ε / γίΛΐ TABLE 18. Group N° of animals Treatment Day Route T01 15 Saline solution 0.28 se, se T02 15 ISC + Pyosilina (PLO) 0.28 in, se T03 15 TXO + Pyosilina (PLO) 0, 28 se, se T04 15 TXO + E. coU + T pyogenes + Pyosilin (PLO) 0.28 se, se Beginning on the day of delivery and continuing for 21 days thereafter, the presence of uterine / vaginal discharge was assessed and if present it was collected and scored, with a score > 2 indicating the presence of metritis. Approximately 30 ml of blood was collected (Study Days 0, 28 and 49), for determination of antibody responses to E. coU, T. pyogenes and pyolysin by ELISA. Any adverse reactions, not otherwise taken as part of the data collection of the procedure, were documented. The primary endpoint was the presence of a mucopurulent uterine / vaginal discharge; a score > 2 would indicate the presence of metritis. Treatment was considered effective if only T01 cows developed clinical metritis, or if the duration of mucopurulent vaginal discharge (score > 2) was significantly shorter (p= <0.1) compared to controls. If it was present, a mucopurulent discharge was collected after delivery. Comparisons between treatments were made at each time point. The least-squares means (back-transformed for serological data), their standard errors, and their 90% confidence intervals were calculated from the least-squares parameters obtained from the analyses. The intervals and numbers of animals with data were calculated for each treatment group at each time point. Collected metritis data (vaginal / uterine discharge present, Yes / No; vaginal / uterine discharge score; clinical signs) were summarized for each animal at each time point, and used to determine the frequency distributions of each category for each treatment at each time point. Frequency distributions of whether an animal was normal / abnormal (normal is a score = 0 or 1; abnormal is a score > 2) for each sign of metritis (eg, vaginal / uterine discharge score) were summarized by treatment. and time point. If an animal had an abnormal uterine discharge score (a score > 2) it was summarized by treatment, and analyzed using a generalized linear mixed model (Proc Glimmix) with a binomial error distribution and a logit link function. The statistical model includes the fixed effect of treatment and the random effect of batch and block within batch. Treatment groups were contrasted (this was repeated for each metritis variable described in this paragraph). If the Glimmix Proc does not converge for a metritis variable, then Fisher's exact test was used instead of treatment group comparison. The duration of an abnormal score (for each metritis variable) was determined for each animal and calculated as (last abnormal time point minus first abnormal time point) + 1. The duration of the abnormal score was set to zero for animals that did not they had time points with an abnormal score for that metritis variable. Abnormal score duration was calculated as (last scheduled data collection time point minus first abnormal time point) + 1 for animals that withdrew from the study before the last scheduled data collection time point for that metritis variable. Abnormal scoring duration was analyzed with a general linear mixed model with fixed effect: treatment and random effects of lot, block within lot, and residual. Linear combinations of parameter estimates were used in a priori contrasts after analysis to determine a significant treatment effect (P < 0.10). Comparisons between treatments were made. The least-squares means, their standard errors, and their 90% confidence intervals were calculated for each treatment group from least-squares parameter estimates obtained from the analyses. Results. All cows that had twins were withdrawn from the study, as ai acnn / i znz / R / YiAi such a case predisposes the cow to metritis and may distort the data. Withdrawn cows included 6 from the T01 control group, 2 each from the T02 and T03 groups, and 1 from the T04 group. For the remaining cows in each group, the incidence of metritis and the estimated days of metritis were calculated. As can be seen in Table 19, the incidence of metritis in the T03 and T04 groups was numerically lower compared to the other groups. The data also indicated that groups T03 and T04 had a shorter duration of metritis in the first 10 days after parturition than animals in groups T01 and T02. Thus, it can be concluded that native pyolisin, either alone or in combination with E. coH and T pyogenes bacterins, when coadjuvanted with TXO, is effective in reducing the incidence of natural metritis in cattle. TABLE 19. Group (N° of animals) Incidence of metritis (%) Estimated days of MMC IC less than 90% IC greater than 90% T01 (8) 100 5.2 3.6 17.3 T02 (13) 100 6.7 5.1 8.7 T03 (13) 84.6 3.7 2.1 6.2 T04 (14) 78.6 3.5 2.0 5.7 EXAMPLE 5, Mastitis vaccines in cattle The E. coli J-5 bacterin is a known antigen for the treatment of mastitis. In this study, different adjuvants combined with J-5 bacterins have been evaluated to determine their antimastitis effects. The study design is summarized in Table 20. Calving took place on day 49. Blood and milk samples were taken on days zero, 7, 28, 35, 49, 63, 70, and 84. Cows were challenged with day 70. ai ocnn / i znz / E / YiAi TABLE 20, Treatment Group Number of Animals Treatment Day Dose Dose Units Route T01 20 Saline 0.28 5.0 mL SC T02 20 Escherichia Coli Bacterin, Strain 1-5 (ENVIROCOR®) 0.28 5.0 mL se T03 20 E. coli TXO 0.28 5.0 ml sc T04 20 E. coli VACCIMAX®-CpG 0 2.0 ml SC T05 20 E. coli VACCIMAX® - Poly I:C 0 2.0 ml sc The duration of the infection caused by E Coli in groups T01-T06 was the following: T01 - 252.1 h, T02 - 213 h, T03- 191.6 h, T04 - 190.2 h, T05 - 198.7 h. . VACCIMAX® treatments provide the shortest duration of infection. VACCIMAX® is an oil-in-water emulsion comprising multilamellar liposomes, in which the antigen is packed between the bilayers of the liposomes. The protective effects of the treatments were also evaluated by determining the stratified mitigated fraction. The greater the stratified mitigated fraction, the greater the protective effect. Again, VACCIMAX® formulations had the greatest effect (13.5 17.19 times more than control), but TXO treatment was also effective (6.24 times more than control). Total antibody responses to J-5-specific IgG in whole cell serum were measured using an indirect capture ELISA. The results are summarized in tables 21 and 22. TABLE 21 contrast stratified mitigated fraction 90% confidence interval T01 vs T02 2.1 -14.9 to 33.3 T01 vs T03 13.1 -15.4 to 62.9 T01 vs T04 30.5 6.4 to 47.9 T01 vs T05 36.1 7.6 to 68 ai acnn / i znz / E / YiAi TABLE 22 Time Point Period 0 Period 1 Period 2 Period 3 Period 4 T01 4996 a 6787 a 4457 a 4049 a 16303 a T02 4425 a 15106 b 12498 bc 20281c 51040 c T03 4815 a 27806 c 2898 2 d 27612 c 49968 c T04 3465 a 17969 bc 7495 ab 6318 ab 22010 ab T05 4477 a 18012 bc 18404 cd 7805 b 17626 ab Period 0=at Ivaccination, l=day 28, 2=day 49, 3=before challenge, 4=end of challenge. Treatment groups with the same letter between each time point are not significantly different at alpha=0.10 EXAMPLE 6: Vaccine against Neosoora Caninum. Neospora caninum is a coccidian parasite that was identified as a species in 1988. It is a major cause of spontaneous abortion in infected cattle. In addition to being a major cause of abortion in cattle, neosporosis is a significant disease in dogs throughout the world. If the disease is detected early, dogs can be successfully treated with clindamycin and other antiprotozoal drugs. However, the disease is often fatal in young puppies. Preventive vaccines have been tested in cattle. A commercially available inactivated vaccine was made but had mixed results. A live vaccine using attenuated N. caninum tachyzoites has been more successful, but is expensive to produce. In this study, the inventors determined the effects of different adjuvants on the properties of a vaccine against N. canimum using cyclophilin (NcCYP) and profilin (NcPro) from N. caninum as antigens. Eight to 10 week old female BALB / c mice were used for this experiment. All animals were immunized twice at 3 week intervals with rNcCyP and rNcProf in the presence of the indicated adjuvant. Three weeks after the second immunization, all animals were sacrificed and spleen and blood were collected. The NcCyP / NcProf-specific proliferative response was determined with a proliferation assay (day 3 to 4). The NcCyP / NcProf-specific cytokine response was determined by stimulating splenocytes with Neospora antigen for 48 h and cytokine levels in the supernatant were determined by cytokine-specific ELISA. Serum antibody levels were determined by ELISA. Animals were treated as summarized in Table 23. Ei ocnn / i znz / E / YiAi TABLE 23 Adjuvant Treatment Amounts (prepared as a 2 mL dose and 1 / 10th of the 2 mL used / mouse dose). Antigen (cyclophilin d Neospora caninui NcCyP) Amount administered mice at one time, ul T01 QCDCRT Quil-A (250 ug / 2 ml), cholesterol (250 ug / 2 ml), DDA (100 ug / 2 ml), Carbopol (0.075 % v / v / 2 ml), R1005 (1,000 ug / 2 ml), CpG (SEQ ID NO: 8; 250 ug / 2 ml) (100 ug / 2 ml dose) 100 T02 TXO CpG (SEQ ID N °: 8; 250 ug / 2 ml), DEAE-dextran (100 mg / 2 ml), mineral oil (50% v / v / 2 ml), SPAN (1.5% v / v / 2 ml), TWEEN 80 ( 7% v / v / 2 ml) NcCyP (100 ug / 2 n doses) 100 T03 TCMO CpG (SEQ ID NO: 8; 250 ug / 2 ml), mineral oil (50% v / v / 2 ml) , SPAN (1.5% v / v / 2 ml), TWEEN 80 (7% v / v / 2 ml), MPLA (25 ug / 2 ml) NcCyP (100 ug / 2 n doses) 100 T04 QCDCRTc Quil-A (250 ug / 2 ml), Cholesterol (250 ug / 2 ml), DDA (100 ug / 2 ml), Carbopol (0.075 % v / v / 2 ml), R1005 (1,000 ug / 2 ml,) with Te = Chimeric ODN / ORN SEQ ID NO: 14 (250 ug / 2 ml) NcCyP (100 ug / 2 n doses) 100 T05 ISCX ISC = ISCOM (100 ug / 2 ml), DEAE-Dextran (100 mg / 2 ml ) NcCyP (100 ug / 2 n doses) 100 T06 Negative Control Normal saline N / A N / A The properties of the above treatment groups are summarized in Table 24. Al QCnn / l 7Π7 / Ε / ΥΙΛΙ TABLE 24 lymphocyte stimulation index (mean+ / SEM) IFNg production by splenocytes (pg / ml) (mean+ / -SEM) Total IgG, OD at 1:16000 (mean+ / -SEM) IgG2a, OD at 1:2000 (mean+ / -SEM) IgGl, OD at 1:2000 (mean+ / - SEM) T01 (QCDCRT) 8.0+ / -7.0 23.0+ / -15.3 0.2076+ / -0.0547 0.6155+ / -0.264 0.3823+ / - 0.03145 T02 (TXO) 62.9 + / -59.0 680.5+ / -446.7 0.279+ / 0.06855 0.6742+ / -0.192 0.7675+ / - 0.08285 T03 (TCMO) 92.1+ / -46.4 961.5+ / -205.5 0.2722+ / -0.0581 0.6 217+ / -0.3393 0.972+ / 0.199359048 T04 (QCDCRTc) 2.2+ / -0.9 18.1+ / -15.0 0.10780 + / 0.01125 0.2584+ / -0.03315 0.4404+ / - 0.0693 T05 (ISCX) 5.4+ / -3.6 84.4+ / - 49.4 0.1313+ / -0.018 0.2255+ / -0.0206 0.6486+ / - 0.23585 T06 (Control) 1+ / -2 12.0+ / -7.3 0.0778+ / -0.0033 0.18127+ / -0.00959 0.22+ / -0.012 Taken together, these data demonstrate superior results obtained using TXO and TCMO. EXAMPLE 7, The effects of different adjuvants on immune responses to reproductive tract infection with ChlamydophUa abortus C. abortus is an intracellulose bacterium that causes abortion in sheep and goats. Infection generally occurs during exposure of untreated sheep to aborted material (eg, placenta, fluids, fetus). The bacterium may be latent in infected ewes until breeding and during mid to late gestation, is present in the placenta, and causes necrotizing placentitis even despite an antibody response. After abortion, ewes are normally immune to reinfection. It is believed that vaccination may be beneficial prior to exposure as it prevents initial infection and prevents harboring of the bacteria in the placenta. An elevated IFNg associated with the antibody response in immunity after abortion is a clue that correlates with protection. IFNg may also be associated with a persistence observed in non-pregnant ewes. Ewes were vaccinated on days zero and 28 and challenged on day 49. Animals were sacrificed on day 63 and necropsied. On day zero, whole blood and vaginal samples were taken for qPCR. Blood samples were taken weekly for serology results and on days zero, 7, 28, and 35 for cytokines and Elispot measurements. The treatment groups are presented in Table 25. Al QCnn / l 7Α7 / Β / ΥΙΛΙ TABLE 25 Adjuvant Group Composition A TCMYO CpG (SEQ ID NO: 8, 100 ug / ds), Cholesterol (100 ug / ds), MPLA (100 ug / ds), Poly I:C (50 ug / ds) thickened with 45 % Mineral Oil with 6.3% SPAN® 80 and QS with TWEEN® 80 (1.45%) and TCXMO CpG Water B (SEQ ID NO: 8, 100 ug / ds), Cholesterol (100 ug / ds), MPLA (100 ug / ds), DEAE-Dextran (100 mg / ds), thickened with 45% mineral oil with 6.3% SPAN® 80 and QS with TWEEN® 80 (1.45%) and water Adjuvant Group Composition C TCMO CpG (SEQ ID NO: 8, 100 ug / ds), cholesterol (100 ug / ds), MPLA (100 ug / ds) thickened with 45% mineral oil with 6.3% SPAN® 80 and QS with TWEEN ® 80 (1.45%) and water D Without adjuvant (saline solution) Normal saline solution E Without vaccination N / A F Neither infection nor vaccination N / A Antigen was prepared from aborted fetal ovine kidney and propagated in McCoy cells. The elementary bodies were purified by centrifugation and sonication. Antigen was fixed at 100 ug / dose in 0.1% formaldehyde in 0.9% sodium chloride for vaccination. TABLE 26 Average DO group on the day: 0 7 14 28 35 42 49 56 63 A 0.055 0.090 0.060 0.192 0.266 0.374 0.314 0.315 0.395 B 0.015 0.052 0.073 0.137 0.204 0.23 4 0.234 0.364 0.460 C 0.057 0.075 0.065 0.217 0.347 0.494 0.481 0.487 0.584 D 0.040 0.079 0.074 0.034 0.079 0.078 0.074 0.044 0.109 E 0.042 0.082 0.056 0.022 0.038 0.032 0.039 0.008 0.170 F 0.051 0.095 0.055 0.016 0.033 0.029 0.038 0.015 0.033 Serology results were obtained using the Chek-it ELISA kit and are summarized in Table 26 above. The expression levels of IFNg, IL-2 and IL-4 were determined in sheep PMBC stimulated with Chlamydia AG. The results are shown in Table 27. ai ocnn / i znz / E / YiAi TABLE 27: Expression levels of IFNg, IL-2 and IL-4 in sheep PMBC stimulated with Chlamydia AG IFNg Group IL-2 IL-4 Day 7 Day 28 Day 35 Day 7 Day 28 Day 35 Day 7 Day 28 Day 35 A 18.08 4.20 10.77 4.79 7.62 8.53 3.26 3.01 1.53 B 1.67 2.05 2.52 4.08 7.35 5 .63 2.26 1.12 3.24 C 1.39 1.77 2.61 1.18 1.78 8.09 1.48 0.94 1.09 D 1.58 4.58 2.70 0.87 2.73 3.27 0.64 1.27 1.24 E 2.52 2.42 2.14 2.53 1.95 1.68 1.44 1.38 1.35 F 0.83 1.20 2.05 0.74 3.13 3.71 1.91 2.11 1.47 The response of ovine PBMC to Chlamydia abortas antigen is summarized in Table 28. TABLE 28: Response of ovine PBMC (peripheral blood mononuclear cells) to antigen of Chlamydia abortus Group Mean SFC x 106 cells Times increase Day 0 Day 28 Day 35 Day 0 Day 28 Day 35 A 20.5 50.0 97.0 1.0 12.1 19.5 B 7.5 38.0 14.0 1.0 26.8 14.0 C 1.0 13.0 33.5 1.0 12.8 2 8.8 D 31.0 49.5 33.5 1.0 33.8 33.8 E 15.5 19.5 6.0 1.0 2.3 0.7 F 10.0 7.0 6.0 1.0 0.8 0.4 Two-way indicates that Group F had a higher amount of leukocytes than Group A and B and that Group E had a significantly higher amount of WBC than Group B. Nodules at times of injection were also analyzed. As expected, Groups A-C had larger nodules than Groups C-D. Among the three adjuvants used (Groups A-C), Group C had the largest nodule size, followed by Group B, followed by Group A. The volume of nodules was determined. Again, groups A-C had larger nodule volumes than group D-F. Among Groups A-C, Group A had the smallest volume. Groups A and B nodules had more hemorrhagic and / or necrotic tissue. Group nodules C had more fibrosis. The cellular characteristics are similar in the three nodules, although Group C may have a more lymphocytic component. EXAMPLE 8, The addition of aluminum to TXO results in improved stability The current TXO mix formulation contains 50 mg / ml DEAE-dextran. Dextran, when present at high concentrations in subcutaneous injections, can cause injection site reactions in animals. Therefore, it is proposed to try varying concentrations of DEAE-dextran to see if safety and good therapeutic values can be obtained without compromising the stability of the vaccine formulation. The characterization and stability tests are important as they inform us if this vaccine can be formulated systematically and with a good shelf life for its manufacture. Viscosity tests are performed over a range of shear rates to look for shear thinning (drop in apparent viscosity with increasing shear rate) or shear thickening (increase in apparent viscosity with increasing shear rate), which is a non-Newtonian fluid flow characteristic. Injection strength trials were performed to ensure that the vaccine will be easy to extract and easy to administer over a large number of doses in the field. Since the immunostimulatory oligonucleotide is not expected to alter the stability of the formulation, adjuvants were not added to the mixtures in this example. AXO (aluminum + dextran + oil) mixtures of variable REHYDRAGEL® (5% to 16%) and DEAE-dextran (50mg / ml - 10mg / ml) concentrations were formulated, tested for viscosity, strength of injection and sedimentation using an XO mix (Dextran + oil) as control. The compositions analyzed were the following: Approximately 10 mL of sample was placed in each of five Corning 15 mL centrifuge tubes and allowed an additional week to observe an accelerated settling effect on the emulsions due to the narrow dimensions of the tubes and conical bottom. Samples were also tested for injectability and viscosity. The results are shown below. ai acnn / i znz / E / YiAi ai acnn / i znz / E / YiAi TABLE 29 LOT Aqueous phase Organic phase DEAEdextran REHY-DRAGEL® 2% w / v of AI2O3 TWEEN 80 PBS 10 mM Mineral oil SPAN 80 124008-65 50 mg / ml 0 1.45 v / v % q.s 45% v / v 6.3% v / v 124008-95 50 mg / mL 5% v / v 1.45 v / v % q.s 45% v / v 6.3% v / v 124008-83 20 mg / mL 10% v / v 1.45 v / v % q.s 45% v / v 6.3% v / v 124008-89 10 mg / mL 16% v / v 1.45 v / v % q.s 45% v / v 6.3% v / v These data indicate that after subjecting the centrifuge tubes to accelerated sedimentation, the mixture with 16% REHYDRAGEL® is the most stable. Furthermore, from the inventors' previous work, it is known that a higher DEAE-dextran concentration is associated with higher viscosities and possible shear thinning. The results of these experiments indicate that the addition of REHYDRAGEL® more than compensates for the anticipated loss in shear thinning (pseudoplastic) properties provided by DEAE-dextran. It was observed that even though the 16% REHYDRAGEL® formulation had a higher injection force, it was not significantly more difficult to inject (injection force for water is 3 N). TABLE 30 Lot Viscosity (cP) Injection Force (Newtons) Sedimentation Observations (Day 7) 124008-65 180 6.5 Thin layer of aqueous phase observed on top 124008-95 160 6.5 Slight sedimentation observed 124008-83 180 6.5 Thin layer of phase watery observed in the upper part 124008-89 180 7.5 No sedimentation observed From the above data, it is evident that the mixture with 16% REHYDRAGEL® and 10 mg / ml DEAE-dextran is optimal for use in vaccine formulations, particularly those requiring free endotoxin binding and / or which may be desired for longer emulsion storage life. EXAMPLE 9, Antigens of BRV, BCV and E coH In this example, the inventors investigate the use of adjuvants of the present invention in vaccines against enteritis. Enteritis is caused by bacterial, viral and / or parasitic infections. Cattle, particularly newborn dairy calves and calves, are vulnerable to calf scours because they are subjected to many stresses during the first hours of life when their immune systems are not fully developed. Loss of fluid from calf scours results in dehydration and often death. Animals that survive calf scours often remain weak and poorly behaved throughout their lives. Agents associated with calf scours include bacteria, particularly E coH K99 and F41, and viruses, such as bovine coronavirus (BCV) and bovine rotavirus (BRV). Ten month old Holstein bulls were used in this study. Animals were seronegative to, or titer low for, E coli (K99 and F41), BRV (B223 and Lincoln), and BCV. The treatment groups were the following: TABLE 31 Group N Adjuvant Antigen Amounts per dose Tr Volume (ml) T01 10 Saline solution N / A SQ 2 T02 10 ROTAVEC® (99 from E coli, G6 from BRV and BCV Mineral oil + Alum NA (commercial product) IM 2 T03 10 Quil A + cholesterol + REHYDRAGEL® (1 5% v / v, 2% AI2O3 w / v) + CpG (SEQ ID NO: 8) Quil-A (500 ug / 2.5 ml dose), cholesterol (200 ug / 2.5 ml of dose), REHYDRAGEL® (15% v / v), CpG (100 ug / 2.5 ml of dose) SQ 2.5 ai acnn / i znz / R / YiAi (continued) Group N Adjuvant Antigen Amounts per dose Tr Volume (ml) T04 10 E. coli K99 / F41; BRV G6 / G10, BCV all inactivated) Quil A + cholesterol + REHYDRAGEL® (15% v / v, 2% AI2O3 w / v) + CpG (SEQ ID NO: 8) + AMPHIGEN® Quil-A (500 ug / 2.5 ml of dose), cholesterol (200 ug / 2.5 ml of dose), REHYDRAGEL® (15% v / v), CpG (100 ug / 2.5 ml of dose), Amphigen (2.5% v / v) SQ 2.5 T05 10 TXO + REHYDRAGEL® (15% v / v, 2% AI2O3 w / v) CpG (100 ug / 5 ml of dose), DEAE-dextran (100 mg / 5 ml of dose), oil mineral (45% v / v), Span (6.3%), Tween (1.45% v / v) SQ 5 T06 10 TO + REHYDRAGEL® (15% v / v, 2% AI2O3 w / v) CpG (100 ug / 5 ml of dose), mineral oil (45% v / v), Span (6.3%), Tween (1.45% v / v), REHYDRAGEL® (15%) SQ 5 Blood samples were collected every 21 days for six months for serology. Injection site reactions were measured on days 0 (pre-vaccination), 1, 2, 3, 7, 14, 21, and every 21 days thereafter. Responses to E. coli K96, E. coli F41, BRV Lincoln, BRV B223, and BCV were measured by quantifying antibody titers on selected days. The results are summarized below (different letters indicate differences in a= 0.1): ai acnn / i znz / R / YiAi TABLE 32 BRV G6 (Lincoln) Geometric Mean Virus Titers (MMC) Target titer > 1255 BRV G10 (B223), Target titer > 1472 BCV, Target titer > 1107 Day 0 Day 21 Day 189 Day 0 Day 21 Day 189 Day 0 Day 21 Day 189 T01 b 142.1 a 208.1 152.3 a 430.5 a 512.1 588.5 a a 238.9 a 430.6 548.8 a T02 b 129.2 b 750.5 349.9 b 530.1 b 1024.2 675.7 ab b 349.8 b 5997.1 1398.9 b T03 140.2 b c 3649.6 533.9 b 532.2 c 2681.9 985.6 ab ab 348.4 b 7299.1 1106.1 b T04 ab 91.4 c 3128.8 575.0 b 492.7 cd 3511.8 1064.3 b ab 298.8 b 7023.0 1448.3 b T05 ab 81.8 4705.6 C 1498.9 c 494.6 e 9089.6 2998.6 c ab 326.3 10085.5 2521.6 c T06 a 39.1 2682.1 C 4706.4 d 456.2 6020.2 d 4683.8 c a 237.2 9556.2 C 2298.9 c Treatments T05 and T06 resulted in the highest antibody titers from day 21 to the end of the study (day 189). In particular, the commercial vaccine (ROTAVEC®) failed, like T05 and T06, in inducing antibodies against the viral components of enteritis. TABLE 33 Group Geometric mean of anti-E coli titers E coli K99 pilus antigen (target > 742) E coli F41 pilus antigen (target determine) Day 0 Day 21 Day 106 Day 189 Day 0 Day 21 Day 106 Day 189 T01 to 35 a 36 a 82 44 a a 187 a 152 a 142 66 a T02 a 41 b 349 4386' 2986 c a 152 c 12801 d 6970 4223 e T03 a 43 be 588 b 686 467 b a 200 b 3200 b 467 200 b T04 to 50 to 588 b 1089 686 b a 147 b 3734 b 800 400 cd T05 a 50 d 1056 3200' 2986 c a 264 c 12801 C 1600 607 d T06 a 54 cd 864 3456 C 1601 c a 216 b 1600 b 800 234 BC Treatments T02 and T05-T06 behaved similarly in developing a response against K 99. Treatment T02 developed the best response to E coli F41. The T05 treatment was the second most effective in developing a response to that antigen. Taken together, these data show that T05 and T06 appear to be the most promising formulations. Both have provided target IgG responses for multiple fractions through day 189. Both T05 and T06 appear to provide superior or equivalent serological efficacy compared to ROTAVEC® (T02, IM) by SQ (subcutaneous) administration. T03 and T04 retained elevated serologic titers for a shorter duration than T05 and T06. Single dose vaccination with T03, T04, T05 and T06 provided serum titers above target level for BRV G6, BRV G10 and BCV. Single dose vaccination with T04, T05 and T06 provided serum titers above the target level for E. coli K99. T04, T05 and T06 maintained antiviral serum titers above target levels for 6 months. T05 and T06 maintained E. coli anti-K99 serum titers above target levels for 6 months. All evaluated formulations demonstrated adequate safety in Holstein bulls. Rectal temperatures were measured on days zero, 1, 2, and 3. Although there were no statistically significant differences between the T01 (control) group and the T02-T06 groups, the differences in temperatures (MMC) were not large (within one degree F). ai ocnn / i ζηζ / Ε / γίΛΐ TABLE 34 * Day 000 Day 001 Day 002 Day 003 T01 101.1 a (38.4) 102.2 ab (39.0) 102.0 a (38.9) 102.3 b (39.1) T02 101.7 b(38.7) 102.6 abc (39.2) 102.2 ab (39.0) 101.8 to (38.8 ) T03 101.8 b (38.8) 102.7 bc (39.3) 102.2 ab (39.0) 101.9 a (38.8) T04 101.3 ab (38.5) 102.8 c (39.3) 102.0 a (38.9) 102.0 ab (38.9) T05 10 1.7 b(38.7) 102.3 abc (39.1) 102.5b (39.2) 102.4b (39.1) T06 101.6ab (38.7) 102.1a (38.9) 102.4b (39.1) 102.1ab (38.9) Preliminary trials of formulations in pregnant dairy cows demonstrated safety. Groups T01, T03 and T05 were analyzed, 5 cows in each group. Thirteen of 15 cows calved, 12 calves were normal, one was stillborn. EXAMPLE 10. Tick vaccine. Experiment design Two vaccine formulations based on the Bm86 antigen were tested. One formulation contained an aqueous builder (QCDCRT) and the other an oil-based builder (TXO), as summarized below. ri acnn / i znz / R / YiAi TABLE 35 Group Antigen Adjuvant Amounts of ingredients T01 N / A None N / A T02 Rhipicephalus microplus (formerly BoophHus) protein rBm86 purified (stock solution, 1.16 mg / mL) QCDCRT 250 ug Quil-A, 250 ug cholesterol, 100 ug DDA, 0.0375% Carbopol, 1,000 ug R1005, 100 ug SEQ ID NO: 8 T03 TXO 100 ug SEQ ID NO: 8 / 100 mg DEAE-dextran in mineral oil (45%), SPAN® 80 (6%) and TWEEN® 80 (1.45%) Twenty-four calves were randomly assigned to one of three treatment groups out of eight calves. Calves in each treatment group were individually vaccinated with 2 ml of either one of the Bm86+ adjuvant formulations or saline (control group). Vaccinations took place on day 0 and 28. On day 41, the cattle were housed in a stall and on day 42 they were infested with 250 mg of R. annu / atus larvae. The ticks used in this study were originally collected from a ranch in Val Verde County, Texas. All withdrawn sated adult females were harvested daily from individual calves on days 63-84. Calves were removed from the barn on day 85. Ticks collected were counted and up to 10 from each calf were weighed and placed in a climate chamber each collection day for 13 days. Spent females were discarded 14 days after collection and the egg mass produced was weighed. Fourteen days after the first hatch, the numbers of hatched and intact eggs were recorded and a percent hatch determination was calculated. Before each injection with vaccine and for the next three days after injection, each calf was monitored for lumps at the injection site and rectal temperatures were taken. Blood serum was collected from each calf on days -7, 0, 14, 28, 42 and 85 for determination of Bm86 antibody titers throughout the study as determined by ELISA. Results Preliminary results show 98.6 and 99.6% control of formulations T02 and T03, which is significantly higher than T01. These percentage control calculations take into account only the reduction in weight of sated females and egg mass. The reduction in hatching percentage will be determined at a later date and added to the final results. One of the 24 calves in the study produces a small lump after each injection (formulation containing the oil adjuvant). The lumps were less than 10 cm in length and 3 cm in depth. The lumps are soft and do not appear to be painful to the animal. There is no increase in rectal temperature in the animals treated throughout the study. The serology results demonstrate statistically significant differences between each of the treatments at the respective time points except that there was no statistical significance (p = 0.114) between QCDCRT and TXO treatments at the 14-day time point. Both QCDCRT and TXO effectively increase BM86 antibody titers at each time point tested. TXO was higher than QCDCRT (p<0.05) at each time point analyzed except day 14 (p = 0.114). Rl ocnn / l 7ΠΖ / Ε / ΥΙΛΙ TABLE 36 Group N BM86 antibody titer, retrotransformed least squares mean (Mean ± SEM) Day 14 Day 28 Day 41 Day 83 T01 8 100±46.42 100±31.52 100±17.05 100±17.31 T02 8 2018±937 1179±372 13532± 2308 4082±707 T03 8 5956±2765 8404±2649 28557±4870 18638±3227 EXAMPLE 11. Foot-and-mouth disease (guinea pigs) The aim of this study was to compare the humoral immune responses in guinea pigs vaccinated with trivalent FMD vaccines adjuvanted with different adjuvant formulations. Guinea pigs were vaccinated on days zero and 28 as summarized in Table 37. At each dose of T03-T07, the antigen was a combination of FMDV Type O (9 ug), A (5 ug) and Asial (5 ug / ml). The antigenic composition of T02 is proprietary information of the manufacturer and therefore was not available. Blood samples for serology study were collected on days -3, 25 and 53. Serum titers of antibodies against serotypes O, A and Asia 1 are summarized below. Although responses against serotypes O and A were low even in the positive control group (T02), the response against Asia 1 was higher in T07 (TXO adjuvant) than in the positive control group and higher than any other treatment. The low responses against serotypes O and A may be due to the presence of low levels of O and A antigens in the formulation. Therefore, the liposome-based VACCIMAX® groups (T03-T05) did not show any significant response against any of the antigens (O, A, Asial). TABLE 37 Al QCnn / l 7Α7 / Β / ΥΙΛΙ Group N adjuvant / ingredients Treatment days Dose RT T01 24 / 22 Saline solution 0, 28 0.2 ml IM T02 24 / 24 Commercial vaccine Raksha monovalent FMDV vaccine (vet) (positive control) Property 0, 28 0.2 ml IM T03 23 / 22 VACCIMAX® S100 / polyI:C SlOO / cholesterol, 12% w / v (60 mg / dose) / Poly I:C 100 pg / dose water in oil, 50% aqueous liposomes + 50% Marcol 52 / Montanide 888 0.28 0.2 mi IM T04 23 / 23 VACCIMAX® S100 / Pam3Cys Property 0.28 0.2 mi IM T05 23 / 22 VACCIMAX® (Biolipon 95) / Pam3Cys VacciMax Biolipon 95, 100 ug / Poly I:C / ds, water in oil, 50% aqueous liposomes + 50% Marcol 52 / Montanide 888 0, 28 0.2 mi IM T06 24 / 24 QCDCRT (80% volume) 250 ug Quil-A, 250 ug cholesterol, 100 ug DDA, 0.0375% Carbopol, 1,000 ug R1005, 100 ug SEQ ID NO: 8 0, 28 0.2 mi IM T07 24 / 23 TXO 100 ug SEQ ID NO: 8; Dextran DEAE 100 mg, 45% mineral oil, 6.3% SPAN®80, 1.45% TWEEN®80, QS water 0.28 0.2 ml IM N represents the number of surviving animals for the first / second vaccination ai acnn / i znz / R / YiAi TABLE 38 Group Serotype O SN titers, geometric mean of titers Serotype A SN titers, geometric mean of titers Serotype Asial SN titers, geometric mean of titers Day -3 Day 28 Day 56 Day -3 Day 28 Day 56 Day -3 Day 28 Day 56 T01 4 4 4.1 4 4 4 4 4.1 4.1 T02 4 9.6 49.9 4 7 14.1 4 14 266.9 T03 4 4.8 13.8 4 4.1 9 4 5.9 24.3 T04 4 4.1 10.3 4 4.5 5.8 4 4.3 9.7 T05 4 4.1 8.1 4 4.5 4.7 4 4.3 13.6 T06 4 4.1 5 4 4 4 4 4.2 5.1 T07 4 5 9 4 5.6 43.1 4 19.8 320.8 EXAMPLE 12. Foot-and-mouth disease (cattle) In this study, the effect of different adjuvants used in a vaccine against FMD in a challenge model was determined. Three adjuvants were studied. The vaccine was an experimental ARS vaccine against FMD in a challenge model developed by PIADC. FMD-LL3B3D-A24 Cruzeiro was used as the antigenic component of the vaccine (10 ug) and wild-type FMDV A-24 Cruzeiro was used as the challenge virus. The antigen has been previously described, for example, in US20120315295 (Rieder et al., filed June 9, 2011 and published December 13, 2012). Briefly, FMD-LL3B3D-A24 Cruzeiro comprises a genetically modified FMDV (foot-and-mouth disease virus). FMDV is genetically modified, that is, it is a leaderless virus containing a deletion of the leader protein coding region (Lpro) such that FMD viruses lacking this protein are attenuated in cattle and pigs. It also comprises mutations (negative markers) introduced into two non-structural viral proteins that result in the deletion of two antigenic epitopes recognized by specific antibodies, one located on the 3B protein and the other on the 3D protein (replaced by the corresponding rhinovirus sequence). bovine that serves as a negative antigenic epitope on these proteins), thus providing two potential targets for DIVA (differentiation of naturally infected from vaccinated animals) serological assays. Four to seven cattle were used in each group. The total volume injected was 2 ml. Animals were vaccinated on day zero by IM injection (2.0 ml per dose) and challenged intradermally on day 21 with wild-type FMDV. Clinical scores were evaluated on days 0, 3, 7 and 10 according to the following scale: No clinical signs: 0, vesicular foot lesion: 1 point for each affected foot. The maximum score is 4. The results of the experiment are as follows: Al ocnn / l 7Π7 / Β / ΥΙΛΙ TABLE 39 Adjuvant Group Details / By Dose Mean Clinical Score Day C Day 3 Day 7 Day 10 T01: Saline N / A 0 3.0 3.5 4.0 T02 MONTANIDE ®ISA 206 VG A mineral oil-based adjuvant that has been developed for the manufacture of water-in-oil-in-water (W / O / W) emulsions. It comprises a high grade injectable mineral oil and an extremely refined emulsifier obtained from mannitol and purified oleic acid of vegetable origin. MONTANIDE® ISA 206 VG does not contain ingredients of animal origin. Exact composition is property of manufacturer (Seppic Inc) 0 0 0 0 T03 QCDCRT (80% by volume) Quil-A 250 ug, Cholesterol 250 ug, DDA 100 ug, Carbopol 0.0375%, R1005 1000 ug, 100 ug of SEQ ID N°: 8 0 1.14 2.86 2.43 T04 TXO 100 ug of SEQ ID N°: 8 / 100 mg of DEAE-dextran in emulsion WO 0 0 0 0 The differences between T01 and T02 and between T01 and T04 were statistically significant. From the table above, it can be concluded that at least based on clinical scoring, TXO adjuvants and MONTANIDE®ISA 206 VG have approximately equal efficacy. However, serology analysis to measure serum neutralizing activity against FMDV-A24 shows that group T04 (TXO adjuvant) had higher titers than group T02 (MONTANIDE®ISA 206 VG). TABLE 40. Least squares means of serum neutralization titrations (back-transformed) ai ocnn / i znz / E / YiAi Time Point Day 0 Day 7 Day 14 Day 21 T01 0.45a 0.45a 0.45a 0.45a T02 0.45a 1.60c 1.13c 1.20b T03 0.45a 1.10b 0.66b 0.61a T04 0.45a 2.21d 2.21d 2 .21d Different letters indicate a statistically significant difference (p<=005) These results demonstrate that the TXO adjuvant was capable of providing 100% protection against a challenge with an FMD-causing agent in cattle and of conferring higher antibody titers than the saline control and the other two adjuvants tested. The amount of FMDV RNA (copies per ml) was determined in nasal swabs and in serum. Data is provided in tables 41-44. Briefly, these data demonstrate that groups T02 and T04 resulted in lower amounts of FMDV in nasal swabs. Between T02 and T04, it should be noted that the animals in the T04 group showed an earlier reduction (or lack of increase) in amounts of FMDV RNA, thus again demonstrating superior properties of the TXO adjuvant. Rl QCnn / l 7Π7 / Β / ΥΙΛΙ TABLE 41. FMDV in nasal swabs (FMDV RNA copy of shedding by mi measured by rRT-PCR; means LSI Time point Day 21 Day 22 Day 23 Day 24 Day 25 Day 26 Day 27 Day 28 Day 29 Day 30 Day 31 T01 1.35 1.75 6.1 6 7.0 9 6.8 8 6.1 3 5.1 9 4.9 8 2.5 1 1.8 1 1.3 5 T02 1.35 1.49 4.6 3 5.3 1 5.6 2 4.1 4 2.2 1 1.8 4 1.5 8 2.6 6 1.8 3 T03 1.35 1.92 3.5 4 4.6 6 5.3 9 5.2 7 3.1 2 1.8 7 1.5 6 1.8 4 1.8 4 T04 1.3 5 1.59 3.9 7 5.0 5 4.4 7 3.7 5 2.3 1 1.6 1 1.5 6 2.5 8 1.5 5 TABLE 42. Statistical significance (nasal swabs! P<=0.05? Day 21 Day 22 Day 23 Day 24 Day 25 Day 26 Day 27 Day 28 Day 29 Day 30 Day 31 T01 v T02 No No Yes Yes No Yes Yes Yes No No No T01 v T03 No No Yes Yes No No Yes Yes No No No T01 T04 No No Yes Yes Yes Yes Yes Yes No No No T02 T03 No No No No No No No No No No T02 T04 No No No No Yes No No No No No No T03 T04 No No No No No Yes No No No No no ai acnn / i ζηζ / Ε / γίΛΐ TABLE 43. Serum FMDV (Viremia FMDV RNA copy by mi measured by rRT-PCR; means LSI Time point Day 21 Day 22 Day 23 Day 24 Day 25 Day 26 Day 27 Day 28 Day 29 Day 30 Day 31 T01 1.35 6.85 8.67 8.56 5.96 3.91 1.77 1.35 1.35 1.35 1.35 T02 1.35 1.58 1.57 1.75 1.83 1.35 1.35 1.35 1.35 1.35 1.35 T03 1.35 3.84 3.77 3.20 2.72 1.82 1.35 1.35 1.35 1.35 1.35 T04 1.35 1.59 1.35 1.35 1.35 1.35 1.35 1.35 1.35 1.35 1.35 TABLE 44. Statistical significance (serum) P<=0.05? Day 21 Day 22 Day 23 Day 24 Day 25 Day 26 Day 27 Day 28 Day 29 Day 30 Day 31 T01 vs T02 No Yes Yes Yes Yes Yes Yes No No No No T01 vs T03 No Yes Yes Yes Yes Yes No No No No No T01 vs T04 No Yes Yes Yes Yes Yes Yes No No No No T02 vs T03 No Yes Yes Yes No No No No No No No T02 vs T04 No No No Yes Yes No No No No No No T03 vs T04 No Yes Yes Yes Yes No no no no no no While all animals in group T01 showed fever after challenge, none of the animals in group T04 had fever. The responses of groups T02 and T03 were contradictory (some animals showed fever and some did not). This observation confirms the conclusion of the overall superiority of TXO compared to the other adjuvants used in this study. EXAMPLE 13: TXO activates cell-mediated immunity Using FMD as an exemplary antigen in the animal model described in the example above, the effect of adjuvants on cell-mediated immunity was tested. Peripheral blood mononuclear cells (PBMC) were purified from bovine whole blood collected on days 4, 7, 14 and 21 post-vaccination. FMDV-specific T cell polyferative responses were assessed using carboxyfluorescein diacetate succinimidyl ester (CFSE) staining. The results are provided in table 45. ai acnn / i znz / E / YiAi TABLE 45. proliferation index f mean ±sd) Treatment / DAY Day 4 Day 7 Day 14 Day 21 T01 l±0 1.22±0.365 1.12±0.070 0.965±0.144 T02 l±0 1.633±1.046 1.813±0.860 4.473±4.012 T03 l±0 1.769±0.877 1.8 50±.980 1.549± 0.608 T04 l±0 1.589±0.682 2.667±1.424 6.757±4.653 These data demonstrate a superior effect of TXO on cell-mediated immunity on both day 14 and day 21. These data also indicate that since cell-mediated immunity is responsible for the duration of immunity, TXO adjuvant may provide a longer duration of immunity than MONTANIDE®ISA 206 VG. EXAMPLE 14. Generation of antibodies for diagnostic use The TXO adjuvant of the present invention was used to generate antibodies for diagnostic use. Briefly, source animals were immunized every 2-4 weeks with formulations comprising TXO-adjuvanted selected recombinant antigens, the composition of which was as follows: SEQ ID NO: 8-125 ug; DEAE-dextran - 125 mg; mineral oil 46.56% v / v of the formulation; TWEEN® 80 - 1.5% v / v of the formulation; SPAN®80 - 6.518% v / v of the formulation. The final volume was 2 ml. Small visible injection site reactions were observed after injections, but were within the anticipated size of reactions. Based on daily observations, the observed rib reactions did not appear to be painful to the goats. Blood samples were collected 2-3 weeks after each immunization and various assays were performed to assess antibody titer. Serology ELISA 5 scores of more than 1000 were considered sufficient to initiate antibody collection. Animals were bled weekly (7.5% blood volume based on body mass). At the conclusion of the study, the goats were euthanized by terminal exsanguinations and blood was also collected for antibody (Ab) collection. If necessary, the animals were assigned to additional studies. Ei ocnn / i znz / E / YiAi TABLE 46: Summary of Goat Polyclonal Reagent Generation Studies Completed ai acnn / ι ζγιζ / β / υιλι Antigen Amount (ug) / dose Source animal (N) Source of Ab Total serum volume collected Immunizations, No. Comments FeLV gp70 100-150 ug Goat (6) serum, milk* 26.7 1 serum, 300 1 milk 15 All goats titrated greater than 2,000,000* HistophHus somni (H. somni) protein p31 150 ug Goat (4) Serum 4.84 1 8 All goats titrated greater than 2,500,000. Two goats titrated greater than 5,000,000 Parainfluenza Virus Protein bovine-3 (BPI-3) HN 61.8 ug Goat (4) Serum 3.19 1 4 All goats had a titer greater than 2000. Three had a titer greater than 8000 Antigen Amount (ug) / dose Source animal (N) Source of Ab Total serum volume collected Immunizations, No. Comments rBVDl E2 (gp53) 150 ug Goat (4) Serum 3.93 1 3 All goats achieved a titer greater than 100000. One goat consistently had titers greater than 1200000 Circovirus antigen canine 150 ug Goat (4) Serum 4.51 1 4 All goats achieved a titer greater than 500,000. Two achieved a titer greater than 2,000,000 Antigen Amount (ug) / dose Animal 1 source(N) Source of Ab Total serum volume collected Immunizations, N° Comments Bordetella FHA protein 100 ug Goat (4) Serum 2.57 1 4 All goats achieved a titer greater than 800,000. Two titrated over 4000000 Parapoxvirus (inactivated) 150 ug Goat (4) Serum 1.35 1 6 All goats titrated over 40000# Rl acnn / l 7Π7 / Β / ΥΙΛΙ * One goat in the group developed a pseudopregnancy and was lactating. 300 I of milk was collected from this goat. #Evaluations deduced from the ELISA test modality. Endpoint titrations were not indicated at this time and the serum was not diluted enough to determine the endpoint. Serum antibodies to FeLV gp70 were successfully purified using either internal protein A or protein G columns, for each small scale purification, or protein G chromatography for large scale purification, at Maine Biotechnology Services (MBS), Portland. , I. Polyclonal antibodies were concentrated using Millipore 30K Ultra filter units to a final concentration of approximately 1 mg / ml. Antibodies against the other antigens reported in Table 46 were crude. The antibodies were isolated from milk obtained from a spontaneously lactating goat immunized with FeLVgp70 according to a procedure comprising the following steps: a) The pH of the milk was titrated to 4.6 with 2 M HCl and stirred at room temperature for 30 minutes for casein precipitation; b) The milk was centrifuged at 17,000 x g for 30 minutes and the supernatant was collected; c) Equilibrium buffer solution was added to the supernatant at 3.3 M NaCI, 0.3 M glycine and 0.2 M Tris base; d) The supernatant was clarified by centrifugation at 3000 x g for 15 minutes; e) The clarified milk supernatant was applied to a MabSelect column equilibrated with the buffer solution from step 'c'; f) The column was washed with equilibration buffer and eluted with 0.15 M glycine, pH 3.0; g) The eluted fractions were neutralized with 0.2 M Na phosphate. As non-limiting examples, procedures for generating anti-PI3 and anti FeLV gp70 are provided below. One of the objectives was to generate goat polyclonal antisera to bovine parainfluenza virus-3 (BPI-3) HN protein for use in in vitro assays. This study was designed to vaccinate goats with a purified bovine parainfluenza virus-3 (BPI-3) HN protein formulated with TXO adjuvant bovine parainfluenza virus-3 (BPI-3) HN protein used as antigen. At approximately seven weeks after the first injection, all four goats were determined to have sufficiently high serum antibody concentrations (SN (seroneneutralization) greater than 1000) to begin production of serum bleeds. The production of bleeds began one week after the fourth immunization. Blood was collected for serum at weekly intervals for three weeks. Sera from each goat were pooled for individual production bleeds. A total of 3,187.50 ml of serum was collected during approximately 3 weeks of production bleeds. Serum was processed and stored at -80°C for evaluation in BPI-3 HN-based assays. All serum collected from three goats (#30, 31, and 35) was thawed at room temperature. Serum from goat number 34 was not used due to low antibody response in the screening ELISA. See Table 47 (Production of PI3-NH Polyclonal Antibodies: SN Response and Antigenic Potency ELISA). Goat number 35, collected on November 20, 13, had the lowest volume of serum available, 117 ml. Thus, 117 mL from each goat for collection was pooled into a sterile 1 L Nalgene PETG bottle. Approximately 1053 mL (9 x 117 mL) of serum was dispensed in 50 mL aliquots into 20 sterile 60 mL Nalgene bottles. PETG and 50 aliquots of 1.0 ml. ai ocnn / i znz / E / YiAi ai acnn / i znz / R / YiAi TABLE 47 Immunization Animal ID with titration SN PI3 30 31 34 35 0 <2 76 <2 <2 1 215 1218 54 362 2 4096 8192 2435 9192 3 8192 16384 2696 9742 As a result, this study successfully generated at the conclusion a total of 3,187.5 ml of whole blood collected from four goats that were repeatedly immunized with a TXO-formulated BPI-3 protein, over a three-week bleed-producing period. Good polyclonal antibody titers were generated in serum. Sufficient amounts of purified reagent were obtained for use in in vitro assay applications. In 2010, the USDA notified industry that the FeLV capture reagent gp85 / 70 used for LEUKOCELL® and VERSIFEL® assays was no longer supplied. Thus, the aim of this study was to generate goat polyclonal antisera to recombinant FeLV gp70 protein for use in in vitro assays. Previous efforts to produce antibodies following a vaccination with Freund's adjuvant were not successful. This study was designed to vaccinate goats with a 444 amino acid fragment of FeLV gp70 protein expressed by recombinant E. coii formulated with adjuvant. Starting with the 4th injection, the injection dose was reduced to 100 pg FeLV gp70 protein (instead of the original dose of 282 pg FeLV gp70 protein). The dose change was made because the starting dose of 282 pg / mL caused a high incidence of injection site reactions. The dose was initially reduced to 100 pg / ml, but then increased to 150 pg / ml at the seventh immunization and maintained at that level until the end of the study (a total of 15 immunizations). PBS buffer was used to make up the difference in dose volume, which was kept at 1 ml. Blood was collected from the goats, and once the sandwich and direct ELISA antibody titers were determined to be high enough, the serum was collected and the polyclonal antibodies were purified. Six healthy female goats of the LaMancha and Alpine breeds that were 1-3 years of age and weighing >100 Ib (45.35 kg) were obtained for use in this study. Goats were fed hay and grain and had free access to water throughout the study. General health observations were made once a day. A 1 ml dose of the experimental vaccine was administered subcutaneously to each goat at 21-day intervals, with a total of 15 immunizations administered to each of the five goats completing the study. Immunizations were initially administered in the neck or hind paw, alternating sides and sites in subsequent immunizations. Small visible reactions were observed at the reaction site after immunizations. The immunization, administered to goats on the loose skin just cranially on the right hind foot, was reported to cause minor swelling, pain, and moderate lameness in all goats the next day. Subsequent injections were given to alternate sides of the neck or area over the ribs and were generally well tolerated. However, the area over the ribs was ultimately found to be the best location tolerated by the goats. At approximately eight weeks after the first injection, four of the six goats (21, 22, 24, 25) were determined to have serum antibody concentrations high enough to begin production bleeds for serum. The production bleeds of the two remaining goats (23, 26) began five weeks later. Blood for serum was collected at weekly intervals. Goat 25 was withdrawn from the study after six weeks of production blood collections. She was limping on arrival and exhibited a persistent limp despite banamine treatment. Euthanasia was specified for terminal bleeding and was administered by site procedure to ensure maximum blood volume collection. Sera from each goat were pooled by individual production bleeds. A total of 26.7 I of serum was collected during approximately 7 months of production bleeds. Goat 24 unexpectedly developed a pseudopregnancy during the study. Milk was collected from this goat for >3 months, with a total of 300 I of milk available for antibody collection. A protocol for high level purification of FeLV gp70 polyclonal antibody from milk was developed. Antibodies were purified on two different dates from 500 ml of pooled serum from goat 24 using protein G affinity chromatography at Maine Biotechnology Services. A total of 6388 mg (321 mL of 19.9 mg / mL) and 7343 mg (348 mL of 21.1 mg / mL) of purified goat anti-FeLV gp70 antibodies were prepared for evaluation in the FeLV-based assay. Blood samples (approximately 25 ml / sample) were collected in 12.5 ml serum separator tubes (SST) fourteen days after each vaccination to determine antibody concentrations to FeLV gp70. The SSTs were labeled with the ID of the goat and the date of collection. Once assays determined that FeLV gp70 antibody titers based on ELISA signal intensity for one animal were at an acceptable concentration, Ei ocnn / i znz / E / YiAi started the production collections of that animal. The volumes of blood drawn from each goat were determined based on the weight of the goat, to obtain the maximum blood volume. IACUC guidelines allow collection of up to 7.5% of blood volume weekly. Blood was collected in 12.5 ml SST for production collections. At the conclusion of the study, the goats were sacrificed by terminal exsanguination and blood was also collected for antibody collection. All tubes were labeled with the goat ID and the date of collection. The blood was allowed to clot at room temperature. After centrifugation, the serum was collected and transferred to polypropylene vials. Different TSS sera collected from the same goat on one collection day were pooled. The serum was kept on ice until shipment for purification. A production summary is provided in table 48. Al QCnn / l 7Α7 / Β / ΥΙΛΙ TABLE 48 Goat ID Weekly Volumes (mi) Terminal Bleeding (mi) Total Production (mi) 21 75-125 1000 4430 22 85-150 875 4665 23 85-125 1000 3630 24 110-200 1580 6785 25 80-105 980 1565 26 125-200 1750 6125 Total 1 Goat 24 produced serum with the highest antibody concentrations of all goats. Antibodies in purified serum from goat 24 compared to USDA 94-06 as a capture reagent using FeLV detection mAb gp70 C11D8 in a sandwich ELISA assay showed a similar dose response. Purified serum from goat 24 was compared to USDA reagent 94-06 by Western blotting for the ability to detect FeLV gp85 / 70 protein. A similar Western blot profile was observed between the current capture, 94-06, and the new goat 24 capture, except that an additional ~15 kD band was observed with the goat 24 capture. Data using the antibody The new capture reagent showed that the current reference has a different dose-response curve shape than the current reagent when used to capture the reference and the test run. Both whey and milk purified anrendati-FeLV gp70 worked well as a capture reagent in FeLV ELISA assays. Additional studies are ongoing, as shown in Table 49. It is expected that each of the formulations (antigens reported in Table 49 and adjuvanted with TXO) will elicit sufficiently high serology titers (greater than 1000, or more preferably greater than 5000, or more preferably greater than 10000, or more preferably, more than 50,000, or more preferably, more than 100,000, or more preferably, more than 250,000, or more preferably, more than 500,000, or most preferably, more than 1,000,000) in at least one animal (preferably at least 2 animals, or more preferably at least three animals, or most preferably all animals treated), thus resulting in a sufficient amount of antibodies for diagnostic or research applications. Al ocnn / l 7Α7 / Β / ΥΙΛΙ TABLE 49 Antigen Amount (ug) / two¡ s Source Animal (N) Ab Source Total Serum Volume Collected Immunizations, No. Clostridium perfringens Alpha-toxin (inactivated) 100 ug Goat (3) Serum 3.31 1 / continuous 10 Beta-toxin from Clostridium perfringens (inactivated) 100 ug Goat (3) Serum 3.93 1 / continuous 9 Epsilon-toxin from Clostridium perfringens (inactivated) 100 ug Goat (3) Serum 4.07 1 / continuous 10 Purified rBVD2 E2 (gp53) protein 150 ug Goat ( 4) Serum 6 / continuous Inactivated whole cell of Brachyspira hyodysenteriae (strain B204) 150 ug Goat (3) Serum 3 / continuous Digestive Pepsin of Brachyspira hyodysenteriae (BR2019-12 strain) 150 ug Goat (3) Serum 3 / continuous All publications cited herein, both patent publications and non-patent publications, are indicative of the level of qualification of those skilled in the art to which the present invention pertains. All such publications are incorporated herein in their entirety by reference to the same extent as if each individual publication were specifically and individually indicated for incorporation by reference. Although the invention herein has been described with reference to 5 particular embodiments, it will be understood that these embodiments are merely illustrative of the principles and applications of the present invention. Therefore, it will be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be designed without departing from the spirit and scope of the present invention as defined by the following claims.
Claims
1. An immunogenic composition, characterized in that it comprises an effective amount of a foot-and-mouth disease virus (FMDV) antigen and an adjuvant formulation comprising an oil phase and an aqueous phase, a polycationic vehicle, and an immunostimulatory oligonucleotide containing CpG, wherein the immunogenic composition is a water-in-oil emulsion.
2. The immunogenic composition according to claim 1, further characterized in that the adjuvant formulation additionally comprises an aluminum hydroxide gel.
3. The immunogenic composition according to claim 1, further characterized in that said oily phase comprises at least 40% v / v of said immunogenic composition.
4. The immunogenic composition according to claim 1, further characterized in that said oily phase comprises at least 45% v / v of said immunogenic composition.
5. The immunogenic composition according to claim 1, further characterized in that said oily phase comprises at least 48% v / v of said immunogenic composition.
6. The immunogenic composition according to any of claims 1 to 5, further characterized in that the polycationic vehicle is DEAE-dextran 7. The immunogenic composition according to any of claims 1 to 6, further characterized in that the foot-and-mouth disease virus antigen is genetically modified.
8. The immunogenic composition according to claim 7, further characterized in that the foot-and-mouth disease virus antigen is a guide virus.
9. The immunogenic composition according to claim 7 or claim 8, further characterized in that the foot-and-mouth disease virus antigen expresses one or more of the FMVD structural proteins of a serotype selected from the group consisting of A, C, O, Asial, SAT1, SAT2, or SAT3.
10. The immunogenic composition according to claim 9, further characterized in that the foot-and-mouth disease virus antigen comprises antigens from multiple FMVD serotypes. (QCnn / l 7A7 / B / YILI) 11. The use of the immunogenic composition as claimed in any of claims 1 to 10 to prepare a vaccine to protect a bovine from FMDV infection.
12. The immunogenic composition according to claim 6, further characterized in that the CpG-containing immunostimulatory oligonucleotide is present in the amount of approximately 50 to approximately 400 gg per dose and the DEAE-dextran is present in the amount of approximately 10 to approximately 300 mg per dose.
13. The immunogenic composition according to claim 12, further characterized in that the CpG-containing immunostimulatory oligonucleotide is present in the amount of approximately 100 to approximately 250 gg per dose and the DEAE-dextran is present in the amount of approximately 50 to approximately 200 mg per dose.
14. The immunogenic composition according to claim 6, further characterized in that the oil is a mineral oil.
15. The immunogenic composition according to claim 14, further characterized in that the CpG-containing immunostimulatory oligonucleotide is present in the amount of approximately 100 to approximately 250 gg per dose and the DEAE-dextran is present in the amount of approximately 50 to approximately 200 mg per dose.
16. The immunogenic composition according to claim 15, further characterized in that the CpG-containing immunostimulatory oligonucleotide is present in the amount of approximately 100 gg per dose and the DEAE-Dextran is present in the amount of approximately 100 mg per dose.
17. The use of the immunogenic composition as claimed in claim 15 to prepare a vaccine to protect a bovine from FMDV infection.
18. The use of the immunogenic composition as claimed in claim 16 to prepare a vaccine to protect a bovine from FMDV infection.
19. The immunogenic composition according to any of claims 1 to 10 for use in protecting a bovine from FMDV infection.
20. The immunogenic composition according to claim 15 for use in protecting a bovine from FMDV infection.
21. The immunogenic composition according to claim 16 for use in the protection of a bovine from FMDV infection.