Correlates of cross-protective immunity to porcine reproductive and respiratory syndrome virus

Authors: VU, HIEP - University Of Nebraska; SUN, HAIYAN - University Of Nebraska; Workman, Aspen; STEFFEN, DAVID - University Of Nebraska; OSORIO, FERNANDO - University Of Nebraska

Submitted to: Research Workers in Animal Diseases Conference Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 9/16/2018
Publication Date: 12/5/2018
Citation: Vu, H.L., Sun, H., Workman, A.M., Steffen, D., Osorio, F. 2018. Correlates of cross-protective immunity to porcine reproductive and respiratory syndrome virus [abstract]. Conference of Research Workers in Animal Diseases Conference, December 1-4, 2018, Chicago, Illinois. Abstract #10. Available: https://crwad.org/proceedings-archive/

Interpretive Summary:

Technical Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) remains one of the most economically important swine pathogens. Current PRRSV vaccines do not confer optimal levels of heterologous protection, presumably due to the substantial genetic variation among PRRSV strains circulating in the field. In addition, they also do not elicit rapid protective immune responses in the vaccinated animals. The overall objectives of this project were to develop a broadly protective modified live vaccine strain against PRRSV and to identify the correlates of cross-protective immunity. Bioinformatics and molecular techniques were employed to generate a fully synthetic PRRSV strain containing a consensus genomic sequence of type 2 PRRSV (designated PRRSV-CON). The PRRSV-CON genome genome was designed in the way that it is located at the center of the phylogenetic tree; thus, it has a balanced genetic distance to all PRRSV strains circulating in the field. Immunization/challenge experiments were conducted in pigs to evaluate the protective efficacy of the synthetic PRRSV strain and to evaluate the immune responses. We demonstrated that the synthetic PRRSV-CON confers unprecedented levels of heterologous protection. However, the synthetic PRRSV-CON at passage 1 is highly virulent; therefore, not suitable to be used as a modified-live vaccine in pigs. Next, we attenuated the PRRSV-CON by continuously passaging the virus in MARC-145 cells, a non-natural host cell line. The attenuated PRRSV-CON confers similar levels of heterologous protection as its parental strain. Finally, we discovered that the synthetic PRRSV-CON possesses a unique phenotype in that it induces type-I interferons (IFNs) instead of suppressing these cytokines. The IFN-inducing phenotype of PRRSV-CON was mapped to the 3.3 kb genomic fragment encoding three viral nonstructural proteins: nsp1a, nsp1b and the N-terminal part of nsp2. The attenuated PRRSV-CON is an excellent candidate for development of the next generation of MLV PRRSV vaccines with improved levels of heterologous protection. Additional experiments are needed to evaluate the relationship between the viral capability of inducing type-I IFNs and the viral ability to confer protection against heterologous PRRSV strains.