Assessment of homologous and heterologous PCV2 vaccine efficacy in a PCV2d/PRRSV co-challenge model.

Porcine circovirus 2 (PCV2) is an economically significant, ubiquitous pathogen affecting the global swine industry. While vaccines have been highly efficacious in controlling clinical disease, questions have arisen in recent years regarding gaps in clinical protection observed in the field due to heterologous PCV2 infection and coinfections with virulent, contemporary porcine reproductive and respiratory syndrome virus (PRRSV) isolates. Therefore, this study evaluated clinical, pathological, and immunological differences in homologous and heterologous PCV2 vaccinated pigs co-challenged with PCV2d and PRRSV. The study closely mimicked field conditions where 21-day-old commercial pigs were vaccinated with a commercial PRRSV vaccine and either a commercial PCV2a or PCV2d vaccine or left as PCV2 unvaccinated controls. Pigs were co-challenged with PCV2d and PRRSV restriction fragment polymorphism (RFLP) 1-7-4 28 days post-vaccination. In addition to significantly higher mortality, the unvaccinated group had significantly higher tissue viral load and viremia in addition to moderate to severe lymphoid depletion with significantly greater PCV2 antigen detected in the lymph nodes, tonsil, and lung compared to both vaccinated groups. While PCV2 vaccination regardless of subtype prevented the development of severe clinical PCVAD in the majority of vaccinates, the PCV2d vaccinates had reduced tissue viral load, significantly lower viremia, and reduced lymphoid depletion with less PCV2 antigen detected in tissues compared to the PCV2a vaccinates. Additionally, approximately 20 % of the PCV2a vaccinates had moderate to severe lymphoid depletion with moderate to severe antigen detection, which is associated with clinical PCVAD. While total levels of PCV2-specific antibodies measured by ELISA were similar between the PCV2a and PCV2d vaccinates, PCV1-2 chimeric virus neutralization assays revealed differential subtype-specific neutralizing antibody (NA) titers among the PCV2a and PCV2d vaccinates. Prior to challenge on day 28 (28 days post-vaccination), PCV2d vaccinates had significantly higher NA titers against the PCV1-2d vaccine and challenge chimeric viruses, while the PCV2a vaccinates had significantly higher NA titers against the PCV1-2a vaccine chimeric virus. Collectively, homologous vaccination may provide greater protection in virulent co-infection scenarios in the field. This study provides further insight into differences in protection elicited by homologous and heterologous vaccination, resulting in valuable insights to enhance PCV2 control strategies in the current PCV2d/PRRSV co-infection paradigm.