The gC1qR Binding Site Mutant PCV2 Is a Potential Vaccine Strain That Does Not Impair Memory CD4⁺ T-Cell Generation by Vaccines

PCV2 has been reported to reduce the protective effects of various vaccines on immunized pigs. Our previous studies showed that the interaction of Cap and host protein gC1qR mediated the PCV2 infection-induced suppression of immune response. Thus, we wondered whether the gC1qR binding site mutant PCV2RmA could be a vaccine strain and whether this mutant PCV2RmA impairs other vaccines. Herein, we showed that PCV2 infection reduced the classic swine fever virus (CSFV) vaccine-induced generation of memory CD4⁺ T cells through the interaction of Cap with gC1qR. PCV2RmA can effectively induce the production of PCV2-specific antibodies, neutralizing antibodies, and peripheral blood lymphocyte proliferation in piglets at the same levels as the commercial inactivated PCV2 vaccine. The PCV2RmA-induced anti-PCV2 immune responses could eliminate the serum virus and would not lead to pathological lesions like wild-type PCV2. Moreover, compared to the commercial inactivated PCV2 vaccine, PCV2RmA is capable of inducing more durable protective immunity against PCV2 that induced production of PCV2-specific antibodies and neutralizing antibodies for a longer time via stronger induction of memory CD4⁺ T cells. Importantly, PCV2RmA infection did not impair the CSFV vaccine-induced generation of memory CD4⁺ T cells. Collectively, our findings showed that PCV2 infection impairs memory CD4⁺ T-cell generation to affect vaccination and provide evidence for the use of PCV2RmA as an efficient vaccine to prevent PCV2 infection. IMPORTANCE PCV2 is one of the costliest pathogens in pigs worldwide. Usage of PCV2 vaccines can prevent the PCV2 infection-induced clinical syndromes but not the viral spread. Our previous work found that PCV2 infection suppresses the host type I interferon innate immune response and CD4⁺ T-cell-mediated Th1 immune response through the interaction of Cap with host gC1qR. Here, we showed that the gC1qR binding site mutant PCV2RmA could effectively induce anti-PCV2 immunity and provide more durable protective immunity against wild-type PCV2 infection in pigs. PCV2RmA would not impair the generation of memory CD4⁺ T cells induced by classic swine fever virus (CSFV) vaccines as wild-type PCV2 did. Therefore, PCV2RmA can serve as a potential vaccine strain to better protect pigs against PCV2 infection.