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How can HIV-type-1-Env immunogenicity be improved to facilitate antibody-based vaccine development?

TitleHow can HIV-type-1-Env immunogenicity be improved to facilitate antibody-based vaccine development?
Publication TypeJournal Article
Year of Publication2012
AuthorsKlasse PJohan, Sanders RW, Cerutti A, Moore JP
JournalAIDS Res Hum Retroviruses
Volume28
Issue1
Pagination1-15
Date Published2012 Jan
ISSN1931-8405
KeywordsAcquired Immunodeficiency Syndrome, AIDS Vaccines, Animals, Antibodies, Neutralizing, DNA, Viral, env Gene Products, Human Immunodeficiency Virus, gag Gene Products, Human Immunodeficiency Virus, HIV Antibodies, HIV-1, Humans
Abstract

No vaccine candidate has induced antibodies (Abs) that efficiently neutralize multiple primary isolates of HIV-1. Preexisting high titers of neutralizing antibodies (NAbs) are essential, because the virus establishes infection before anamnestic responses could take effect. HIV-1 infection elicits Abs against Env, Gag, and other viral proteins, but of these only a subset of the anti-Env Abs can neutralize the virus. Whereas the corresponding proteins from other viruses form the basis of successful vaccines, multiple large doses of HIV-1 Env elicit low, transient titers of Abs that are not protective in humans. The inaccessibility of neutralization epitopes hinders NAb induction, but Env may also subvert the immune response by interacting with receptors on T cells, B cells, monocytes, macrophages, and dendritic cells. Here, we discuss evidence from immunizations of different species with various modified Env constructs. We also suggest how the divergent Ab responses to Gag and Env during infection may reflect differences in B cell regulation. Drawing on these analyses, we outline strategies for improving Env as a component of a vaccine aimed at inducing strong and sustained NAb responses.

DOI10.1089/AID.2011.0053
Alternate JournalAIDS Res. Hum. Retroviruses
PubMed ID21495876
PubMed Central IDPMC3251839
Grant ListAI 36082 / AI / NIAID NIH HHS / United States
AI 45463 / AI / NIAID NIH HHS / United States
P01 AI061093 / AI / NIAID NIH HHS / United States
R01 AI057653 / AI / NIAID NIH HHS / United States
R01 AI074378 / AI / NIAID NIH HHS / United States
R01 AI074378-06 / AI / NIAID NIH HHS / United States
U01 AI095613 / AI / NIAID NIH HHS / United States
U19 AI096187 / AI / NIAID NIH HHS / United States

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