HIV-1 envelope (Env)-based vaccines have so far largely failed to induce antibodies that prevent HIV-1 infection. One factor proposed to limit the immunogenicity of cell-associated Env is its low level of expression on the cell surface, restricting accessibility to antibodies. Using a vaccinia prime/protein boost protocol in mice, we explored the immunologic effects of mutations in the Env cytoplasmic tail (CT) that increased surface expression, including partial truncation and ablation of a tyrosine-dependent endocytosis motif. After vaccinia primes, CT-modified Envs induced up to 7-fold higher gp120-specific IgG, and after gp120 protein boosts, they elicited up to 16-fold greater Tier-1 HIV-1 neutralizing antibody titers, although results were variable between isolates. These data indicate that the immunogenicity of HIV-1 Env in a prime/boost vaccine can be enhanced in a strain-dependent manner by CT mutations that increase Env surface expression, thus highlighting the importance of the prime in this vaccine format.

迄今为止，基于HIV-1包膜（Env）的疫苗在很大程度上未能诱导出可预防HIV-1感染的抗体。建议限制细胞相关Env免疫原性的一个因素是其在细胞表面的低水平表达，限制了抗体的可及性。在小鼠中使用痘苗素初免/蛋白质加强方案，我们探索了Env胞质尾部（CT）中增加表面表达的突变的免疫学效应，包括酪氨酸依赖性内吞作用基序的部分截短和消融。接种牛痘后，CT修饰的Envs诱导的gp120特异性IgG最高提高7倍，gp120蛋白增强后，它们引起的Tier-1 HIV-1中和抗体效价最高提高16倍，尽管分离株之间的结果各不相同。