Department of Medicine/Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, USA.
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
J Virol. 2018 Mar 14;92(7). doi: 10.1128/JVI.00038-18. Print 2018 Apr 1.
Zika virus (ZIKV), which can cause devastating disease in fetuses of infected pregnant women, can be transmitted by mosquito inoculation and sexual routes. Little is known about immune protection against sexually transmitted ZIKV. In this study, we show that previous infection through intravaginal or subcutaneous routes with a contemporary Brazilian strain of ZIKV can protect against subsequent intravaginal challenge with a homologous strain. Both routes of inoculation induced high titers of ZIKV-specific and neutralizing antibody in serum and the vaginal lumen. Virus-specific T cells were recruited to and retained in the female reproductive tract after intravaginal and subcutaneous ZIKV infection. Studies in mice with genetic or acquired deficiencies in B and/or T cells demonstrated that both lymphocyte populations redundantly protect against intravaginal challenge in ZIKV-immune animals. Passive transfer of ZIKV-immune IgG or T cells significantly limited intravaginal infection of naive mice, although antibody more effectively prevented dissemination throughout the reproductive tract. Collectively, our experiments begin to establish the immune correlates of protection against intravaginal ZIKV infection, which should inform vaccination strategies in nonpregnant and pregnant women. The recent ZIKV epidemic resulted in devastating outcomes in fetuses and may affect reproductive health. Unlike other flaviviruses, ZIKV can be spread by sexual contact as well as a mosquito vector. While previous studies have identified correlates of protection for mosquito-mediated infection, few have focused on immunity against sexual transmission. As exposure to ZIKV via mosquito bite has likely occurred to many living in areas where ZIKV is endemic, our study addresses whether this route of infection can protect against subsequent sexual exposure. We demonstrate that subcutaneous ZIKV infection can protect against subsequent vaginal infection by generating both local antiviral T cell and antibody responses. Our research begins to define the immune correlates of protection for ZIKV infection in the vagina and provides a foundation for testing ZIKV vaccines against sexual transmission.
寨卡病毒（ZIKV）可导致感染孕妇胎儿出现严重疾病，可通过蚊虫接种和性途径传播。目前对于性传播 ZIKV 的免疫保护知之甚少。在这项研究中，我们表明，通过阴道内或皮下途径感染来自巴西的当代 ZIKV 株可以预防随后的同源株阴道内挑战。两种接种途径都在血清和阴道腔中诱导了高滴度的 ZIKV 特异性和中和抗体。在阴道内和皮下接种 ZIKV 后，病毒特异性 T 细胞被募集并保留在女性生殖道中。在 B 和/或 T 细胞遗传或获得性缺陷的小鼠研究中，研究表明淋巴细胞群体在 ZIKV 免疫动物中对阴道内挑战具有冗余保护作用。ZIKV 免疫 IgG 或 T 细胞的被动转移可显著限制幼稚小鼠的阴道内感染，尽管抗体更有效地阻止了其在生殖道中的传播。总的来说，我们的实验开始确定针对阴道内 ZIKV 感染的免疫相关性，这将为非孕妇和孕妇的疫苗接种策略提供信息。最近的 ZIKV 疫情给胎儿带来了毁灭性的后果，可能会影响生殖健康。与其他黄病毒不同，ZIKV 可通过性接触和蚊虫媒介传播。虽然以前的研究已经确定了针对蚊虫介导感染的保护相关因素，但很少有研究关注针对性传播的免疫。由于通过蚊虫叮咬接触 ZIKV 的可能性已经发生在许多生活在 ZIKV 流行地区的人中，因此我们的研究旨在确定这种感染途径是否可以预防随后的性暴露。我们证明，皮下 ZIKV 感染可以通过产生局部抗病毒 T 细胞和抗体反应来预防随后的阴道感染。我们的研究开始确定阴道内 ZIKV 感染的免疫保护相关因素，并为测试针对性传播的 ZIKV 疫苗提供了基础。
