Trivalent nucleoside-modified mRNA vaccine yields durable memory B cell protection against genital herpes in models
Trivalent nucleoside-modified mRNA vaccine yields durable memory B cell protection against genital herpes in models
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DOI：
10.1172/jci152310
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发表时间：
2021-12-01
影响因子：
15.9
通讯作者：
Friedman, Harvey M.
中科院分区：
文献类型：
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作者：
Awasthi, Sita;Knox, James J.;Friedman, Harvey M.
由于COVID-19，核苷修饰的mRNA疫苗获得了全球关注。我们评估了一种类似的疫苗方法，用于预防慢性潜伏性生殖器感染，而不是急性呼吸道感染。我们使用动物模型来比较HSV-2三价核苷修饰的mRNA疫苗与制备为蛋白质的相同抗原，重点是抗原特异性记忆B细胞应答和保护的免疫相关性。在豚鼠中，血清中和抗体滴度较高，在1个月和下降远低于8个月的mRNA相比，蛋白免疫的动物。免疫后1个月感染时，两种疫苗均能保护动物免于死亡和生殖器病变;然而，8个月后感染时，mRNA组的保护作用比蛋白组更持久，这一间隔占动物寿命的15%以上。血清和阴道中和抗体滴度与感染保护相关，通过感染后2天生殖器病变和阴道病毒滴度测量。在小鼠中，mRNA疫苗在免疫后的早期比蛋白疫苗产生更多的抗原特异性记忆B细胞，并持续长达1年。高中和滴度和强大的B细胞免疫记忆可能解释了HSV-2 mRNA疫苗更持久的保护作用。
Nucleoside-modified mRNA vaccines have gained global attention because of COVID-19. We evaluated a similar vaccine approach for preventing a chronic, latent genital infection rather than an acute respiratory infection. We used animal models to compare an HSV-2 trivalent nucleoside-modified mRNA vaccine with the same antigens prepared as proteins, with an emphasis on antigen-specific memory B cell responses and immune correlates of protection. In guinea pigs, serum neutralizing-antibody titers were higher at 1 month and declined far less by 8 months in mRNA-compared with protein-immunized animals. Both vaccines protected against death and genital lesions when infected 1 month after immunization; however, protection was more durable in the mRNA group compared with the protein group when infected after 8 months, an interval representing greater than 15% of the animal's lifespan. Serum and vaginal neutralizing-antibody titers correlated with protection against infection, as measured by genital lesions and vaginal virus titers 2 days after infection. In mice, the mRNA vaccine generated more antigen-specific memory B cells than the protein vaccine at early times after immunization that persisted for up to 1 year. High neutralizing titers and robust B cell immune memory likely explain the more durable protection by the HSV-2 mRNA vaccine.