Simian Immunodeficiency Virus Infection Evades Vaccine-Elicited Antibody Responses to V2 Region
Simian Immunodeficiency Virus Infection Evades Vaccine-Elicited Antibody Responses to V2 Region
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DOI：
10.1097/qai.0000000000000530
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发表时间：
2015-04-15
影响因子：
3.6
通讯作者：
Chen, Zhiwei
中科院分区：
文献类型：
--
作者：
Guo, Jia;Zuo, Teng;Chen, Zhiwei
目的：有效的艾滋病疫苗应能引起针对HIV/猴免疫缺陷病毒（SIV）感染的保护性抗体应答。我们最近报道，粘膜引发与复制的改良牛痘天坛病毒（MVTTgpe）为基础的疫苗方案诱导持久的保护，对致病性SIVmac 239感染恒河猴。方法：构建了一个新的SIVmac 239囊膜糖蛋白酵母表面展示抗原库，并对该库进行了验证，以定位猴血清中主要抗原决定簇（MAD）。结果和结论：酵母表面展示文库可以绘制SIV特异性的线性和构象MAD。基于MVTTgpe的方案诱导主要靶向覆盖整个gp 160的6个抗原结构域的抗体。重要的是，与基于Ad 5gpe的疫苗和SIVmac 239感染相比，该方案诱导了针对可变区2（V2）中的不同MAD的独特优势抗体应答。该MAD与较高滴度的抗V2抗体应答相关，其与峰值和设定点病毒载量呈负相关。出乎意料的是，致病性SIVmac 239攻击逃避了疫苗引发的抗V2抗体应答。病毒感染将抗V1 V2抗体主要导向V1区，而不是回忆B细胞对V2 MAD的记忆反应。此外，抗V1 V2抗体反应显着减少感染猕猴后，他们进入猴艾滋病阶段。我们的研究结果对艾滋病疫苗工作具有重要意义，重点是V2区域。
Objectives: An effective AIDS vaccine should elicit protective antibody responses against HIV/simian immunodeficiency virus (SIV) infection. We recently reported that mucosal priming with a replicating modified vaccinia Tiantan virus (MVTTgpe)-based vaccine regimen induces durable protection against pathogenic SIVmac239 infection in rhesus monkeys. Here, we aim to conduct a comprehensive analysis on antigenic determinants recognized by specific antibody responses generated by vaccination and SIVmac239 infection.Methods: A novel yeast surface displayed antigen library of entire SIVmac239 envelope (Env) glycoprotein was established and validated to map the major antigenic determinants (MAD) in monkey sera elicited by vaccination and infection. MAD-directed antibody responses were further analyzed for correlation of protection.Results and Conclusions: The yeast surface displayed library allows the mapping of SIV-specific linear and conformational MAD. The MVTTgpe-based regimen induces antibodies targeting mainly to 6 antigenic domains covering the entire gp160. Critically, this regimen induced a uniquely predominant antibody response against a distinct MAD in variable region 2 (V2) as compared with the Ad5gpe-based vaccine and SIVmac239 infection. This MAD was associated with a higher titer of anti-V2 antibody responses, which was inversely correlated with peak and set-point viral loads. Unexpectedly, the pathogenic SIVmac239 challenge evaded the vaccine-elicited anti-V2 antibody response. Instead of recalling B-cell memory responses to the V2 MAD, viral infection directed anti-V1V2 antibodies primarily to V1 region. Moreover, the anti-V1V2 antibody responses diminished significantly in infected macaques after they enter the stage of simian AIDS. Our findings have critical implications to AIDS vaccine efforts with focus on V2 region.