Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138.
Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139.
Proc Natl Acad Sci U S A. 2021 Mar 2;118(9). doi: 10.1073/pnas.2018338118.
A vaccine which is effective against the HIV virus is considered to be the best solution to the ongoing global HIV/AIDS epidemic. In the past thirty years, numerous attempts to develop an effective vaccine have been made with little or no success, due, in large part, to the high mutability of the virus. More recent studies showed that a vaccine able to elicit broadly neutralizing antibodies (bnAbs), that is, antibodies that can neutralize a high fraction of global virus variants, has promise to protect against HIV. Such a vaccine has been proposed to involve at least three separate stages: First, activate the appropriate precursor B cells; second, shepherd affinity maturation along pathways toward bnAbs; and, third, polish the Ab response to bind with high affinity to diverse HIV envelopes (Env). This final stage may require immunization with a mixture of Envs. In this paper, we set up a framework based on theory and modeling to design optimal panels of antigens to use in such a mixture. The designed antigens are characterized experimentally and are shown to be stable and to be recognized by known HIV antibodies.
一种能有效对抗 HIV 病毒的疫苗被认为是解决当前全球 HIV/AIDS 疫情的最佳方法。在过去的三十年中，人们已经尝试了无数次来开发一种有效的疫苗，但收效甚微，这主要是由于病毒的高度变异性。最近的研究表明，一种能够引发广泛中和抗体（bnAbs）的疫苗有望预防 HIV。这种疫苗被认为至少需要经历三个不同的阶段：第一，激活适当的前体 B 细胞；第二，沿着产生 bnAbs 的途径引导亲和力成熟；第三，优化 Ab 反应以高亲和力结合多样化的 HIV 包膜（Env）。最后一个阶段可能需要用混合的 Env 进行免疫接种。在本文中，我们建立了一个基于理论和模型的框架，用于设计此类混合物中使用的最佳抗原组合。设计的抗原通过实验进行了表征，并显示出稳定性和被已知的 HIV 抗体识别。
