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A nonfucosylated variant of the anti-HIV-1 monoclonal antibody b12 has enhanced Fc?RIIIa-mediated antiviral activity in vitro but does not improve protection against mucosal SHIV challenge in macaques.


ABSTRACT: Eliciting neutralizing antibodies is thought to be a key activity of a vaccine against human immunodeficiency virus (HIV). However, a number of studies have suggested that in addition to neutralization, interaction of IgG with Fc gamma receptors (Fc?R) may play an important role in antibody-mediated protection. We have previously obtained evidence that the protective activity of the broadly neutralizing human IgG1 anti-HIV monoclonal antibody (MAb) b12 in macaques is diminished in the absence of Fc?R binding capacity. To investigate antibody-dependent cellular cytotoxicity (ADCC) as a contributor to Fc?R-associated protection, we developed a nonfucosylated variant of b12 (NFb12). We showed that, compared to fully fucosylated (referred to as wild-type in the text) b12, NFb12 had higher affinity for human and rhesus macaque Fc?RIIIa and was more efficient in inhibiting viral replication and more effective in killing HIV-infected cells in an ADCC assay. Despite these more potent in vitro antiviral activities, NFb12 did not enhance protection in vivo against repeated low-dose vaginal challenge in the simian-human immunodeficiency virus (SHIV)/macaque model compared to wild-type b12. No difference in protection, viral load, or infection susceptibility was observed between animals given NFb12 and those given fully fucosylated b12, indicating that Fc?R-mediated activities distinct from Fc?RIIIa-mediated ADCC may be important in the observed protection against SHIV challenge.

SUBMITTER: Moldt B 

PROVIDER: S-EPMC3372207 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Eliciting neutralizing antibodies is thought to be a key activity of a vaccine against human immunodeficiency virus (HIV). However, a number of studies have suggested that in addition to neutralization, interaction of IgG with Fc gamma receptors (FcγR) may play an important role in antibody-mediated protection. We have previously obtained evidence that the protective activity of the broadly neutralizing human IgG1 anti-HIV monoclonal antibody (MAb) b12 in macaques is diminished in the absence of  ...[more]

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