PMID- 36212883 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221011 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 13 DP - 2022 TI - Heterologous vaccine immunogenicity, efficacy, and immune correlates of protection of a modified-live virus porcine reproductive and respiratory syndrome virus vaccine. PG - 977796 LID - 10.3389/fmicb.2022.977796 [doi] LID - 977796 AB - Although porcine reproductive and respiratory syndrome virus (PRRSV) vaccines have been available in North America for almost 30 years, many vaccines face a significant hurdle: they must provide cross-protection against the highly diverse PRRSV strains. This cross-protection, or heterologous vaccine efficacy, relies greatly on the vaccine's ability to induce a strong immune response against various strains-heterologous immunogenicity. Thus, this study investigated vaccine efficacy and immunogenicity of a modified live virus (MLV) against four heterologous type 2 PRRSV (PRRSV-2) strains. In this study, 60 pigs were divided into 10 groups. Half were MOCK-vaccinated, and the other half vaccinated with the Prevacent((R)) PRRS MLV vaccine. Four weeks after vaccination, groups were challenged with either MOCK, or four PRRSV-2 strains from three different lineages-NC174 or NADC30 (both lineage 1), VR2332 (lineage 5), or NADC20 (lineage 8). Pre-and post-challenge, lung pathology, viral loads in both nasal swabs and sera, anti-PRRSV IgA/G, neutralizing antibodies, and the PRRSV-2 strain-specific T-cell response were evaluated. At necropsy, the lung samples were collected to assess viral loads, macroscopical and histopathological findings, and IgA levels in bronchoalveolar lavage. Lung lesions were only induced by NC174, NADC20, and NADC30; within these, vaccination resulted in lower gross and microscopic lung lesion scores of the NADC20 and NADC30 strains. All pigs became viremic and vaccinated pigs had decreased viremia upon challenge with NADC20, NADC30, and VR2332. Regarding vaccine immunogenicity, vaccination induced a strong systemic IgG response and boosted the post-challenge serum IgG levels for all strains. Furthermore, vaccination increased the number of animals with neutralizing antibodies against three of the four challenge strains-NADC20, NADC30, and VR2332. The heterologous T-cell response was also improved by vaccination: Not only did vaccination increase the induction of heterologous effector/memory CD4 T cells, but it also improved the heterologous CD4 and CD8 proliferative and/or IFN-gamma response against all strains. Importantly, correlation analyses revealed that the (non-PRRSV strain-specific) serum IgG levels and the PRRSV strain-specific CD4 T-cell response were the best immune correlates of protection. Overall, the Prevacent elicited various degrees of efficacy and immunogenicity against four heterologous and phylogenetically distant strains of PRRSV-2. CI - Copyright (c) 2022 Proctor, Wolf, Brodsky, Cortes, Frias-De-Diego, Almond, Crisci, Negrao Watanabe, Hammer and Kaser. FAU - Proctor, Jessica AU - Proctor J AD - Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States. FAU - Wolf, Iman AU - Wolf I AD - Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States. FAU - Brodsky, David AU - Brodsky D AD - Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States. FAU - Cortes, Lizette M AU - Cortes LM AD - Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States. FAU - Frias-De-Diego, Alba AU - Frias-De-Diego A AD - Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States. FAU - Almond, Glen W AU - Almond GW AD - Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States. FAU - Crisci, Elisa AU - Crisci E AD - Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States. FAU - Negrao Watanabe, Tatiane Terumi AU - Negrao Watanabe TT AD - Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States. FAU - Hammer, James M AU - Hammer JM AD - Elanco Animal Health, Greenfield, IN, United States. FAU - Kaser, Tobias AU - Kaser T AD - Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States. LA - eng PT - Journal Article DEP - 20220923 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC9537733 OTO - NOTNLM OT - correlates of protection (CoP) OT - immunity OT - pig OT - porcine reproductive and respiratory syndrome virus (PRRSV) OT - swine OT - vaccination COIS- The funding was sponsored by the Prevacent manufacturer-Elanco Animal Health. Author JH, working for Elanco Animal Health, helped during necropsy including the scoring of gross pathology; however, JH was blinded to the groups to ensure that any potential bias does not influence the data. Apart from this, the sponsors had no role in the execution, interpretation, or writing of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/10/11 06:00 MHDA- 2022/10/11 06:01 PMCR- 2022/09/23 CRDT- 2022/10/10 04:21 PHST- 2022/06/24 00:00 [received] PHST- 2022/08/16 00:00 [accepted] PHST- 2022/10/10 04:21 [entrez] PHST- 2022/10/11 06:00 [pubmed] PHST- 2022/10/11 06:01 [medline] PHST- 2022/09/23 00:00 [pmc-release] AID - 10.3389/fmicb.2022.977796 [doi] PST - epublish SO - Front Microbiol. 2022 Sep 23;13:977796. doi: 10.3389/fmicb.2022.977796. eCollection 2022.