Progress 07/01/06 to 06/30/07
Outputs
OUTPUTS: Vaccines against PRRS virus are limited by the natural variation of the virus itself. This project used genomic sequencing and allied analyses to investigate why immunity to one strain of PRRS virus does not protect pigs against infection with other strain. This project disseminated information about the underlying genetic basis for this phenomenon. The study disseminated information to the scientific and stakeholder communities that will facilitate the development of PRRS vaccines with improved efficacy. The most significant output is a set of linear T-cell epitopes that is now available to the vaccine research community for further testing as vaccine candidates.
PARTICIPANTS: Dr. Kapil Vashisht, PhD, undertook this project as part of his PhD training. The project provided a unique training opportunity for this graduate student involved to conduct research at the interface of PRRS molecular epidemiology and immunology. The project also provided a unique professional development opportunity for this student (who is a DVM) by enhancing his interactions with industry stakeholders.
TARGET AUDIENCES: Results were recently targeted to the audience at the 2007 International PRRS Symposium in Chicago, IL in the form of a poster presentation. Scientists, pharmaceutical industry representatives, government representatives, and producer group representatives were in attendance.
Impacts
The project combined molecular epidemiological analysis of PRRSV field isolates PRRS-IL-006 - PRRS-IL-015 with existing data from controlled laboratory experiments to test the hypothesis that protective immunity to porcine reproductive and respiratory syndrome virus is strain specific, and to identify regions of the viral genome responsible for this strain specificity. Epidemiological analyses involved sequencing of PRRSV variants from persistently infected farms and correlating viral genomic changes with changes in host immunity and clinical disease. Existing, supplemental data involved exposing swine to attenuated virus and, subsequently, to unattenuated autogenous or heterogenous virus; indices of strain specific immunity and clinical disease were then be measured over 35 days in order to determine the relationship between immunity to a particular PRRSV variant and clinical protection against a genetically divergent variant. By combining data sources, this project
has discovered that immunity to PRRS is only weakly cross-protective, and that certain epitopes in the viral gp5 envelope protein are likely determinants of the strength of cross protection. Specifically, work from this study identified three linear T-cell epitopes on gp5 that are conserved among divergent PRRSV variants. These epitopes are promising candidates for future vaccine research efforts.
Publications
- Vashisht, K., Husman, R. J., Zuckermann, F. A. and Goldberg, T. L. (2008). Identification of peptides containing immunodominant glycoprotein 5 T cell epitopes of two porcine reproductive and respiratory syndrome virus strains. Vaccine, in review.
- Vashisht, K., Lager, K. M., Zuckermann, F. A. and Goldberg, T. L. (2008). Variable immunogenicity among PRRS virus strains: implications for cross-protection following vaccination. Vaccine, in preparation.
- Vashisht, K., Husmann, R., Zuckermann, F. A. and Goldberg, T. L. (2007). Identification of peptides containing immunodominant glycoprotein 5 T cell epitopes of two porcine reproductive and respiratory syndrome virus strains. International PRRS Symposium, Chicago, Illinois.
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