期刊
CURRENT OPINION IN HIV AND AIDS
卷 12, 期 3, 页码 294-301出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/COH.0000000000000367
关键词
adeno-associated virus gene therapy; alternative HIV vaccine; bispecific antibody; eCD4-Ig
资金
- NIAID Ruth L. Kirschstein NRSA [F32 AI122980]
- National Institutes of Health [P01 AI100263, R37 AI091476]
- Bill and Melinda Gates Foundation [OPP1132169]
- Bill and Melinda Gates Foundation [OPP1132169] Funding Source: Bill and Melinda Gates Foundation
Purpose of review Here we discuss recently developed HIV-1 entry inhibitors that can target multiple epitopes on the HIV-1 envelope glycoprotein (Env), with an emphasis on eCD4-Ig. Some of these inhibitors are more potent and broader than any single antibody characterized to date. We also discuss the use of recombinant adenoassociated virus (rAAV) vectors as a platform for long-term expression of these inhibitors. Recent findings Much of the exterior of HIV-1 Env can be targeted by broadly neutralizing antibodies (bNAbs). Recent studies combine the variable regions or Fabs from different bNAbs, often with the receptor-mimetic components, to create broad, potent, and hard-to-escape inhibitors. rAAV vectors can express these inhibitors for years in vivo, highlighting their ability to prevent or treat HIV-1 infection. Summary By targeting multiple epitopes on Env, bispecific and antibody-like inhibitors can be broader and more potent than bNAbs. These inhibitors can provide long-term protection from, and perhaps suppression of, HIV-1 if they are administered by a delivery platform, like rAAV vectors, but only after rAAV limitations are addressed.
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