SBIR-STTR Award

Swine morbidity and mortality caused by porcine reproductive and respiratory syndrome (PRRS) virus is a threat to the U.S. pork industry causing losses of $664 million last year that may exceed $700 million in 2014. Vaccines against PRRS virus have failed to stem the occurrence of PRRS in U.S. herds. Here we propose to ascertain the technical feasibility of developing an effective autogenous (killed virus) vaccine. Aptimmune's approach to prepare an atuogenous PRRS virus vaccine consists of using the proprietary porcine alveolar macrophage cell line, named ZMAC, as the cell substrate for both the isolation of field PRRS virus from a clinical sample and the production of the PRRS virus stocks to produce the viral antigen for the vaccine. Since the ZMAC cell line can be used to reliably and swiftly produce autogenous PRRS vaccines from wild-type (field) PRRS virus, it provides to Aptimmune a major competitive advantage. Since the ZMAC cell line is of the same species as the animal in which the vaccine will be used we have termed this new class of PRRS autogenous vaccine as Homologous Cell Autogenous Vaccine (HCAV).We have selected several commercially available adjuvants to formulate our HCAV. We will test these alternative vaccine formulations for their ability to stimulate virus-inhibitory immunity. We expect that our strategy to explore several alternative formulations of a PRRS HCAV will lead to the identification of an effective autogenous vaccine capable of eliciting strong levels of protective immunity against PRRS virus. The expected results of Phase I include: 1) a process for production of an autogenous virus vaccine starting from a clinical sample in 5 weeks or less; 2) identify an optimal formulation for a PRRS HCAV that elicits strong virus inhibitory immunity. The expected outcome is the development of a production process to manufacture in a timely manner an effective autogenous vaccine against PRRS virus. Ultimately, the commercial availability of an effective autogenous PRRS vaccine should result in application of effective management strategies that successfully control the spread of PRRS virus and incidence of PRRS outbreaks. The availability of an effective vaccine against PRRS will mitigate the significant economic impact that this disease has to the American pork industry and thus increase its profitability.

Porcine reproductive and respiratory syndrome (PRRS) virus first appeared in the United States of America in the late 1980's and causes a disease characterized by reproductive failure in sows and significant respiratory distress in growing and finishing swine. Being a major economic problem for the pork industry, the National Pork Board (NPB) considers the control and elimination of PRRS virus from swine commercial herds a top priority. Convincing evidence of the need for new tools to combat PRRS is best illustrated by the significant increase in the prevalence of PRRS in U.S. swine population over the last several years. At present, more than 70% of the swine-herds in the U.S are infected with North American type (genotype 2) PRRS virus, causing economic loses of over $664 million annually, making it the costliest disease to the pork industry. The steady increase in the incidence of PRRS occurred despite the introduction of at least three commercial modified live vaccines for PRRS virus to the U. S. market. These vaccines provide protective immunity for PRRS virus strains that are highly homologous but limited protection against genetically divergent strains. This concept has its foundation on the fact that the genome of PRRS virus in the field is highly diverse and is constantly undergoing a high rate of mutation. Thus, the difficulty of generating PRRS vaccines that have a high level of genetically homology to a given field virus resides in the fact that fully licensed vaccines, based on either modified live or killed viruses requires several years of development followed by a few more years of regulatory testing to be approved for sale by the USDA. Thus, by the time a vaccine is approved and released for commercial use, its genome, and its composition, has become antiquated due to the genetic diversification of the myriad of field virus variants whose genome have substantially evolved over time by mutation. In addition, their use presents some risks including the shedding of vaccine virus, which infects non-vaccinated pigs, persistent viral infection and the potential of reversion of the attenuated vaccine to its original wild-type virulent phenotype. As a rational approach to solve the problem of the high antigenic diversity exhibited by PRRS virus in the field, which makes the development of an effective vaccine difficult, the aim of this phase II project is to complete our studies aimed at ascertaining the technical feasibility of developing an effective autogenous (killed virus) vaccine for PRRS. Based on the results obtained in Phase I, our approach for identifying an efficacious autogenous vaccine is to use modern technologies to formulate vaccines that will be delivered via the respiratory mucosa. Autogenous biologics are custom inactivated vaccines consisting of herd specific antigens derived from a pathogen isolated from the same herd that will be immunized. Because the pathogens constituting this type of product are inactivated (killed) they are considered safe. Autogenous vaccines are prepared using a virus isolated from animal(s) of an infected herd, to be used in the herd of origin, thus, the viral antigens contained in the vaccine will perfectly match the viral antigens expressed by the virus that is causing disease. Importantly, the USDA Center for Veterinary Biologics (CVB) approves the use of autogenous products only when commercially licensed product are not available, or when commercially licensed products have not provided adequate protection, as is the case with PRRSV vaccines. Aptimmune has identified a significant need for an effective autogenous PRRS vaccine, by designing a vaccine specifically formulated for newborn piglets, we are aiming to position our product in this underserved market. Our product is being designed to be delivered via the respiratory mucosa to stimulate immunity at the point of virus entry. This feature will also negate the possibility of the vaccine antigen being blocked