Non-human Primate Immunogenicity Studies of HIV-1 immunogens

HIV-1包膜糖蛋白（Env）的遗传多样性仍然是开发基于抗体的艾滋病疫苗的主要障碍。 在先前的研究中，我们检查了恒河猴免疫后的中和抗体（NAb）反应的广度和幅度与DNA引物重组腺病毒（rAd）加强疫苗编码单一或多个遗传上遥远的Env免疫原。 使用标准化的多层参考Env假病毒组进行NA B评估，我们发现，与用单一Env免疫原（进化枝B或C）免疫的猴相比，用Env免疫原混合物（进化枝A、B和C）免疫的猴在接种疫苗和攻毒后表现出更大的针对中和敏感性第1层病毒的NA B活性。 然而，所有Env疫苗接种猴组均仅表现出有限的2级假病毒中和活性，这更具有循环HIV-1中和敏感性的特征。 另外的免疫原性研究正在评估具有新的Env插入物和各种形式的可溶性Env蛋白的载体。正在评估新抗原，即基于已知中和表位的结构设计。

The genetic diversity of HIV-1 envelope glycoproteins (Env) remains a major obstacle to the development of an antibody-based AIDS vaccine. In prior studies, we examined the breadth and magnitude of neutralizing antibody (NAb) responses in rhesus monkeys after immunization with DNA prime-recombinant adenovirus (rAd) boost vaccines encoding either single or multiple genetically distant Env immunogens. Using a standardized multi-tier panel of reference Env pseudoviruses for NAb assessment, we showed that monkeys immunized with a mixture of Env immunogens (clades A, B, and C) exhibited a greater breadth of NAb activity against neutralization sensitive Tier 1 viruses following both vaccination and challenge compared to monkeys immunized with a single Env immunogen (clade B or C). However, all groups of Env-vaccinated monkeys demonstrated only limited neutralizing activity against Tier 2 pseudoviruses, which are more characteristic of the neutralization sensitivity of circulating HIV-1. Additional immunogenicity studies are evaluating vectors with new Env inserts and various forms of soluble Env proteins. New antigens, structure based design of known neutralizing epitopes, are being evaluated.