Vaccine Research Center, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA.
Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21710, USA.
Cell Rep. 2020 Aug 4;32(5):107981. doi: 10.1016/j.celrep.2020.107981.
The HIV fusion peptide (FP) is a promising vaccine target. FP-directed monoclonal antibodies from vaccinated macaques have been identified that neutralize up to ∼60% of HIV strains; these vaccinations, however, have involved ∼1 year with an extended neutralization-eclipse phase without measurable serum neutralization. Here, in 32 macaques, we test seven vaccination regimens, each comprising multiple immunizations of FP-carrier conjugates and HIV envelope (Env) trimers. Comparisons of vaccine regimens reveal FP-carrier conjugates to imprint cross-clade neutralizing responses and a cocktail of FP conjugate and Env trimer to elicit the earliest broad responses. We identify a signature, appearing as early as week 6 and involving the frequency of B cells recognizing both FP and Env trimer, predictive of vaccine-elicited breadth ∼1 year later. Immune monitoring of B cells in response to vaccination can thus enable vaccine insights even in the absence of serum neutralization, here identifying FP imprinting, cocktail approach, and early signature as means to improve FP-directed vaccine responses.
HIV 融合肽（FP）是一种很有前途的疫苗靶点。从接种疫苗的猕猴中鉴定出了针对 FP 的单克隆抗体，这些抗体能够中和多达 60%的 HIV 株；然而，这些疫苗接种需要大约 1 年的时间，并经历了一个延长的中和潜伏期，在此期间没有可测量的血清中和作用。在这里，我们在 32 只猕猴中测试了七种疫苗接种方案，每种方案都包括多次 FP 载体缀合物和 HIV 包膜（Env）三聚体的免疫接种。疫苗方案的比较揭示了 FP 载体缀合物能够产生跨群中和反应，而 FP 载体缀合物和 Env 三聚体的混合物则能够引发最早的广泛反应。我们确定了一个特征，早在第 6 周就出现了，涉及识别 FP 和 Env 三聚体的 B 细胞的频率，这可以预测大约 1 年后疫苗引发的广度。因此，即使在没有血清中和作用的情况下，对疫苗接种反应的 B 细胞进行免疫监测也可以提供疫苗的见解，这里确定了 FP 印迹、鸡尾酒方法和早期特征是提高 FP 定向疫苗反应的方法。
