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Dendritic cell-targeted porcine reproductive and respiratory syndrome virus (PRRSV) antigens adjuvanted with polyinosinic-polycytidylic acid (poly (I:C)) induced non-protective immune responses against heterologous type 2 PRRSV challenge in pigs

Author:
Subramaniam, Sakthivel, Piñeyro, Pablo, Derscheid, Rachel J., Madson, Darin M., Magstadt, Drew R., Meng, Xiang-Jin
Source:
Veterinary immunology and immunopathology 2017 v.190 pp. 18-25
ISSN:
0165-2427
Subject:
Porcine reproductive and respiratory syndrome virus, adjuvants, blood serum, immune response, immunoglobulin G, interferon-gamma, lungs, polyinosinic-polycytidylic acid, porcine reproductive and respiratory syndrome, recombinant antibodies, structural proteins, swine, vaccines, viral antigens, viral load, viremia, viruses
Abstract:
Porcine Reproductive and Respiratory Syndrome (PRRS) is an economically important swine viral disease worldwide. Current modified live-attenuated vaccines are ineffective against heterologous strains of PRRS virus (PRRSV) circulating in the field. In this study, we evaluated three dendritic cell (DC)-targeted vaccine candidates for their protective efficacy against heterologous PRRSV challenge. Ectodomain regions of DNA-shuffled structural proteins GP3, GP4, GP5 and M of PRRSV were fused together to form the vaccine antigen which was in turn fused with one of three recombinant antibodies each specific to a DC receptor: DC-SIGN, Langerin, and DEC205. The recombinant antibody-fused vaccine antigens were co-administered with polyinosinic-polycytidylic acid (poly (I:C)) adjuvant and subsequently challenged with a heterologous type 2 PRRSV strain (NADC20) in pigs. Our results demonstrate that pigs in DC-SIGN- and DEC205-targeted, but not Langerin- and non-targeted, vaccine groups showed significant IFN-γ- and IL-4-specific CD4T cell immune responses against the vaccine antigen in 7days post-challenge. Pigs in DC-SIGN- and Langerin-targeted vaccine groups showed greatly reduced IgG responses as compared to the DEC205- and non-targeted vaccine groups. The immune responses induced by DC-targeted vaccines did not reduce viremia and lung pathological lesions in type 2 PRRSV-challenged pigs. In contrast, pigs in Langerin-targeted vaccine group showed significantly increased serum viral titers and viral antigen in lung tissues at 7 and 14days post-challenge respectively. In conclusion, specific targeting of PRRSV antigen through DC-SIGN or DEC205 or Langerin-specific antibodies in the presence of poly (I:C) adjuvant induced immune responses that failed to protect pigs against heterologous type 2 PRRSV challenge.
Agid:
5733840