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Increased surface expression of HIV-1 envelope is associated with improved antibody response in vaccinia prime/protein boost immunization
Ist Teil von
Virology (New York, N.Y.), 2018-01, Vol.514, p.106-117
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2018
Link zum Volltext
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
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.
•Novel HIV Env cytoplasmic tail (CT) modifications increase surface expression.•Vaccinia vector vaccination with CT-modified Envs induces high gp120-specific IgG.•gp120 boosts in mice primed with CT-modified Envs induce high Tier-1 Nabs.