Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, 100 Piedmont Ave SE, Atlanta, GA, 30303, USA.
Sci Rep. 2018 May 17;8(1):7807. doi: 10.1038/s41598-018-25960-1.
Broadly neutralizing antibodies (bnAbs) are correlated with passive HIV/SHIV protection and are desirable components of a HIV protective immunity. In the current study, we have designed a sequential-immunization strategy with a panel of envelope glycoprotein (Env)-enriched virus-like particles (VLPs) from various HIV-1 clades (A-E) to elicit bnAbs with high breadth and potency of neutralization in rabbits. We have compared this regimen with repetitive immunizations of individual Env (subtype B) VLPs or a mixture of various Env VLPs. Our results demonstrate that the sequential immunization group of animals induced significantly higher IgG endpoint titers against respective HIV Env (autologous) antigen than other control groups. Animals vaccinated sequentially showed an increase in the antibody endpoint titers and IgG antibody secreting cells (ASCs) against Con-S Env protein. Sequential immunizations with various Env VLPs promoted antibody avidity indices and enhanced bnAb responses against a panel of HIV pseudotyped virions including some of the tier 3 pseudostrains. Sequential immunizations with various VLPs displaying "native-like" HIV-1 Envs elicited bnAb responses with increased breadth and potency of neutralization.
广泛中和抗体（bnAbs）与被动 HIV/SHIV 保护相关，是 HIV 保护性免疫的理想组成部分。在本研究中，我们设计了一种用来自不同 HIV-1 群（A-E）的包膜糖蛋白（Env）富集病毒样颗粒（VLPs）的组合进行序贯免疫的策略，以在兔体内诱导具有广泛中和广度和效力的 bnAbs。我们将该方案与重复免疫个体 Env（亚型 B）VLPs 或各种 Env VLPs 的混合物进行了比较。我们的结果表明，与其他对照组相比，序贯免疫组的动物对各自的 HIV Env（同源）抗原诱导出显著更高的 IgG 终点滴度。接种疫苗的动物的抗体终点滴度和针对 Con-S Env 蛋白的 IgG 抗体分泌细胞（ASCs）增加。用各种 Env VLPs 进行序贯免疫可提高抗体亲和指数，并增强针对包括一些 3 级假病毒株在内的一组 HIV 假型病毒的 bnAb 反应。用展示“天然样”HIV-1 Envs 的各种 VLPs 进行序贯免疫可诱导具有更高中和广度和效力的 bnAb 反应。
