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Limited or no protection by weakly or nonneutralizing antibodies against vaginal SHIV challenge of macaques compared with a strongly neutralizing antibody.

TitleLimited or no protection by weakly or nonneutralizing antibodies against vaginal SHIV challenge of macaques compared with a strongly neutralizing antibody.
Publication TypeJournal Article
Year of Publication2011
AuthorsBurton DR, Hessell AJ, Keele BF, Klasse PJohan, Ketas TA, Moldt B, D Dunlop C, Poignard P, Doyle LA, Cavacini L, Veazey RS, Moore JP
JournalProc Natl Acad Sci U S A
Volume108
Issue27
Pagination11181-6
Date Published2011 Jul 5
ISSN1091-6490
KeywordsAIDS Vaccines, Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Female, HIV Antibodies, HIV Envelope Protein gp120, HIV Envelope Protein gp41, HIV Infections, HIV-1, Humans, Immunization, Passive, Macaca mulatta, Membrane Glycoproteins, Molecular Sequence Data, SAIDS Vaccines, Simian Acquired Immunodeficiency Syndrome, Simian immunodeficiency virus, Vagina, Viral Envelope Proteins
Abstract

To guide vaccine design, we assessed whether human monoclonal antibodies (MAbs) b12 and b6 against the CD4 binding site (CD4bs) on HIV-1 gp120 and F240 against an immundominant epitope on gp41 could prevent vaginal transmission of simian HIV (SHIV)-162P4 to macaques. The two anti-gp120 MAbs have similar monomeric gp120-binding properties, measured in vitro, but b12 is strongly neutralizing and b6 is not. F240 is nonneutralizing. Applied vaginally at a high dose, the strongly neutralizing MAb b12 provided sterilizing immunity in seven of seven animals, b6 in zero of five animals, and F240 in two of five animals. Compared with control animals, the protection by b12 achieved statistical significance, whereas that caused by F240 did not. For two of three unprotected F240-treated animals there was a trend toward lowered viremia. The potential protective effect of F240 may relate to the relatively strong ability of this antibody to capture infectious virions. Additional passive transfer experiments also indicated that the ability of the administered anti-gp120 MAbs to neutralize the challenge virus was a critical influence on protection. Furthermore, when data from all of the experiments were combined, there was a significant increase in the number of founder viruses establishing infection in animals receiving MAb b6, compared with other nonprotected macaques. Thus, a gp120-binding, weakly neutralizing MAb to the CD4bs was, at best, completely ineffective at protection. A nonneutralizing antibody to gp41 may have a limited capacity to protect, but the results suggest that the central focus of HIV-1 vaccine research should be on the induction of potently neutralizing antibodies.

DOI10.1073/pnas.1103012108
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID21690411
PubMed Central IDPMC3131343
Grant ListAI1055332 / AI / NIAID NIH HHS / United States
AI33292 / AI / NIAID NIH HHS / United States
HHSN266200400088C. / / PHS HHS / United States
R01 AI033292 / AI / NIAID NIH HHS / United States
R37 AI055332 / AI / NIAID NIH HHS / United States
R37 AI36082 / AI / NIAID NIH HHS / United States
U19 AI76982 / AI / NIAID NIH HHS / United States

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