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 neut... More
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.
