SIV infection duration largely determines broadening of neutralizing antibody response in macaques
SIV infection duration largely determines broadening of neutralizing antibody response in macaques
复制标题
SIV 感染持续时间很大程度上决定了猕猴中和抗体反应的范围
DOI：
10.1172/jci139123
复制
发表时间：
2020
影响因子：
15.9
通讯作者：
Hirsch Vanessa M.
中科院分区：
文献类型：
--
作者：
Wu Fan;Ourmanov Ilnour;Kirmaier Andrea;Leviyang Sivan;LaBranche Celia;Huang Jinghe;Whitted Sonya;Matsuda Kenta;Montefiori David;Hirsch Vanessa M.
广泛中和抗体(BNAbs)在HIV感染中的发展是病毒和抗体长期共同进化相互作用的结果。了解这种相互作用如何促进感染期间中和广度的增加，将改善艾滋病疫苗战略的设计方式。本文以SIV感染的恒河猴为模型，研究了NAB逃逸变异体感染恒河猴后中和广度的发展，并对NAB应答和病毒进化的动力学进行了评价。我们发现，在感染过程中，感染猕猴对逃逸变异体产生了逐步的NAB反应，并增加了中和广度。此外，中和广度的增加与感染持续时间有关，但与接种物的性质、病毒载量或感染期间的病毒多样性无关。这些结果表明，感染持续时间是推动bNAbs发生的主要因素。这些数据表明了新的免疫策略的重要性，通过模拟长期感染来诱导有效的NAB反应来对抗艾滋病毒感染。
The development of broadly neutralizing antibodies (BNAbs) in HIV infection is a result of long-term coevolutionary interaction between viruses and antibodies. Understanding how this interaction promotes the increase of neutralization breadth during infection will improve the way in which AIDS vaccine strategies are designed. In this paper, we used SIV-infected rhesus macaques as a model to study the development of neutralization breadth by infecting rhesus macaques with longitudinal NAb escape variants and evaluating the kinetics of NAb response and viral evolution. We found that the infected macaques developed a stepwise NAb response against escape variants and increased neutralization breadth during the course of infection. Furthermore, the increase of neutralization breadth correlated with the duration of infection but was independent of properties of the inoculum, viral loads, or viral diversity during infection. These results imply that the duration of infection was the main factor driving the development of BNAbs. These data suggest the importance of novel immunization strategies to induce effective NAb response against HIV infection by mimicking long-term infection.