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Virology. 2018 Jan 15;514:106-117. doi: 10.1016/j.virol.2017.10.013. Epub 2017 Nov 22.

Increased surface expression of HIV-1 envelope is associated with improved antibody response in vaccinia prime/protein boost immunization.

Author information

1
Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
2
Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
3
Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
4
Department of Pharmaceutics, University of Washington, Seattle, WA, USA.
5
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
6
Department of Pharmaceutics, University of Washington, Seattle, WA, USA; Washington National Primate Research Center, University of Washington, Seattle, WA, USA.
7
Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: dreww@mail.med.upenn.edu.

Abstract

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.

KEYWORDS:

Antibody; Cytoplasmic tail; Envelope; HIV; Vaccine; Vaccinia

PMID:
29175625
PMCID:
PMC5770335
DOI:
10.1016/j.virol.2017.10.013
[Indexed for MEDLINE]
Free PMC Article

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