The gC1qR Binding Site Mutant PCV2 Is a Potential Vaccine Strain That Does Not Impair Memory CD4+ T-Cell Generation by Vaccines
The gC1qR Binding Site Mutant PCV2 Is a Potential Vaccine Strain That Does Not Impair Memory CD4+ T-Cell Generation by Vaccines
复制标题
gC1qR 结合位点突变体 PCV2 是一种潜在的疫苗株，不会损害疫苗产生的记忆 CD4 T 细胞
DOI：
10.1128/jvi.00959-22
复制
发表时间：
2022-09-19
影响因子：
5.4
通讯作者：
Huang, Yong
中科院分区：
文献类型：
--
作者：
Du, Qian;Yang, Xuefeng;Huang, Yong
据报道，PCV2可降低各种疫苗对免疫猪的保护作用。我们之前的研究表明，Cap与宿主蛋白gC1qR的相互作用介导了PCV2感染诱导的免疫反应抑制。因此，我们想知道gC1qR结合位点突变体PCV2RmA是否可能是一种疫苗菌株，以及这种突变体PCV2RmA是否会损害其他疫苗。本研究表明，PCV2感染通过Cap与gC1qR的相互作用，减少了经典猪瘟病毒（CSFV）疫苗诱导的记忆性CD4(+) T细胞的产生。PCV2RmA能有效诱导仔猪产生PCV2特异性抗体和中和抗体，并能使仔猪外周血淋巴细胞增殖达到与PCV2市产灭活疫苗相同的水平。pcv2rma诱导的抗PCV2免疫反应能够清除血清病毒，不会像野生型PCV2那样导致病理病变。此外，与商业灭活PCV2疫苗相比，PCV2RmA能够诱导更持久的针对PCV2的保护性免疫，通过更强的记忆性CD4(+) T细胞诱导PCV2特异性抗体的产生和中和抗体的时间更长。重要的是，PCV2RmA感染并未损害CSFV疫苗诱导的记忆性CD4(+) T细胞的产生。总之，我们的研究结果表明，PCV2感染会损害记忆性CD4(+) t细胞的产生，从而影响疫苗接种，并为使用PCV2RmA作为预防PCV2感染的有效疫苗提供了证据。PCV2是全世界猪群中代价最高的病原体之一。使用PCV2疫苗可以预防PCV2感染引起的临床综合征，但不能预防病毒传播。我们之前的工作发现PCV2感染通过Cap与宿主gC1qR的相互作用抑制宿主I型干扰素先天免疫应答和CD4(+) t细胞介导的Th1免疫应答。本研究表明，gC1qR结合位点突变体PCV2RmA可以有效诱导抗PCV2免疫，并对猪野生型PCV2感染提供更持久的保护性免疫。PCV2RmA不会像野生型PCV2那样破坏经典猪瘟病毒（CSFV）疫苗诱导的记忆性CD4(+)T细胞的产生。因此，PCV2RmA可以作为一种潜在的疫苗株，更好地保护猪免受PCV2感染。
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.