Animal vaccines are commonly produced by several routes. Commercially developed vaccines are produced for use in all animals, in many different locations. Such a vaccine would contain antigen and could be derived from a biotype of the pathogenic agent. Different isolates can be biotyped by a variety of typing techniques where a variant of the pathogenic agent is distinguishable by a particular characteristic over other members of the pathogenic species. These variants may differ, for example, by sequence variation of a DNA sequence, RNA sequence, pathogenic response, serological type or the like. See Sambrook et al, Molecular Cloning: A Laboratory Manual, Third editions, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. 2001. Another example of biotyping is glycan typing as is described at Harris et al., U.S. Pat. No. 7,622,254, incorporated herein by reference in its entirety. In the example of influenza virus, the viral strains are analyzed genetically and antigenically by the World Health Organization and the Center for Disease Control by screening numerous influenza viruses circulating in the human and animal populations. A vaccine strain is updated when there is an antigenic difference between the vaccine strain and newly emerged strain of two units in the hemagglutination-inhibition assay. Autogenous vaccines on the other hand are those produced for use at a particular location and group of animals. The pathogenic agent such as a virus is isolated and the whole virus used in producing a vaccine customized for the biotypes found at that location and which may be used at other locations where there may be exposure to such biotype. By way of example, an autogenous vaccine in a veterinary setting may be developed by isolating a virus at a farm to be used as a vaccine at the farm.
The present vaccine options for animals lack an ability to adapt quickly to new outbreaks of disease. Livestock animal diseases cost producers billions of dollars each year in both treatment and lost productivity. For certain diseases, such as those affecting aquatic invertebrates, there is no commercially available vaccine for the key pathogens (such as those affecting farmed shrimp). Porcine Reproductive Respiratory Virus (PRRSV) alone costs the swine industry an estimated $560 M annually. Neumann E J, Kleibenstein J, Johnson C, Mabry J W, Bush E J, Seitzinger A H, Green A L, Zimmerman J J (2005), Assessment of the economic impact of porcine reproductive and respiratory syndrome on swine production in the United States, Journal of the American Veterinary Medical Association 227: 385-392. Swine producers and veterinarians lack a broadly-effective vaccine for PRRS due to the lack of cross-protection commercial vaccines provide against heterologous strains of the pathogen. Influenza is another example of costly disease that affects humans, birds, swine and other animals. Veterinarians identified influenza as a swine disease during the influenza pandemic of 1918 when a connection was made between outbreaks in humans and swine that were closely related in time. According to the International Society for Infectious Diseases, the virus was initially isolated from pigs in 1930, with isolation from humans following in 1934. Influenza is grouped into three categories, based on the absence of serologic cross reactivity between their internal proteins: influenza A, B and C. Influenza A viruses are further classified into groups by antigenic differences of hemagglutinin and neuraminidase proteins. There are sixteen subtypes of HA and nine of NAs known, including H1, H2, H3, N1 and N2. The influenza viruses change frequently as a result of changes in the HA and NA amino acid sequence, allowing the virus to escape being neutralized by the immune response of the body. For example, to date the more prevalent subtypes circulating in human, poultry and swine populations in North America are H1 and H3. In 2008/2009 a new isolate was discovered which has resulted in another pandemic among humans, known as H1N1. This is why when vaccines are prepared from a particular strain it may not provide protection against an outbreak from a different strain, thus requiring vaccines to be prepared anew each year from predicted new or expected isolates.
Thus a vaccine specific for specific biotypes of pathogens in a particular location such as on a farm is highly desirable. Companies exist which specialize in such autogenous vaccines. However, currently all autogenous vaccines are whole-organism preparations which must be inactivated (killed vaccines). In brief, a pathogen is isolated from an animal/farm, purified, grown in a laboratory, formulated, and returned to the farm for vaccination of animals. These traditional autogenous vaccines attempt to address the problem of strain variation; however they are not produced fast enough to have an immediate impact on production and economic losses caused by the disease and are not compatible with diagnostic tests for differentiating infected from vaccinated animals (DIVA).
Vaccine strains in USDA Center for Veterinary Biologics approved commercial vaccines can be ‘switched out’ in approximately 12 months. Rapp-Gabrielspm V J, Sornsen S, Nitzel G, et al. Updating swine influenza vaccines. AASV 39th Annual Meeting Proceedings 2008; 261:264. Vaccine strains in autogenous vaccines can be ‘switched out’ more quickly, possibly within 3-6 months; however, the cost of preparing vaccines with new and updated strains for limited orders may limit availability. Order size may increase with regional/adjacent autogenous networks but may be complicated to organize and implement. Henry S., Swine influenza virus—efforts to define and implement regional immunization. AASV Proceedings 2009; 475:478. VCPR vaccines may be authorized/produced by veterinarians/producers. ‘Switch out’ of vaccine strains can be done more rapidly than by either USDA CVB approved commercial or autogenous vaccines. (See 9 CFR 107.1 regarding Veterinary Client Patient relationship arrangements (VCPR) and 9 CFR 113.113 regarding autogenous vaccines; see also Ryan Vander Veen, Kurt Kamrud, Mark Mogler, et al. Rapid Development of an Efficacious Swine Vaccine for Novel H1N1. PLoS Currents Influenza 2009 November 2RRN1123.) In sum, there are at least three major deficiencies in current vaccines.    1. Specificity. Commercial vaccines do not account for strain variation of pathogens that change quickly in the field. Strain variation and lack of adequate cross-protection lead to vaccine failure and thus production/economic losses.    2. Timeliness. It can take one year to change a commercial vaccine to account for strain variation. Current autogenous vaccines seek to address the problem of specificity, but can take months to prepare from the time a new strain is identified to the time the first animals are vaccinated. For example, traditional killed autogenous vaccines for PRRSV currently available can take up to six months to prepare. In this time frame a new strain of the pathogen can emerge, thus decreasing the value/effectiveness of the autogenous vaccine. A faster way to produce autogenous vaccines is thus needed.    3. Components. All current autogenous vaccines are whole-organism in that the entire pathogen is included in the vaccine. In most diseases this is unnecessary since the specific antigens needed for protection are already known. Also, since the whole virus is contained in the vaccine, they are not compatible with differential diagnostic tests.
Thus there is a need for improved vaccines for animals.
All references cited herein are incorporated herein by reference. Examples are provided by way of illustration and not intended to limit the scope of the invention.
USPTO Backgrounds
USPTO Backgrounds