Vaccine induced antibodies to the first variable loop of human immunodeficiency virus type 1 gp120, mediate antibody-dependent virus inhibition in macaques.

Journal Article (Journal Article)

The role of antibodies directed against the hyper variable envelope region V1 of human immunodeficiency virus type 1 (HIV-1), has not been thoroughly studied. We show that a vaccine able to elicit strain-specific non-neutralizing antibodies to this region of gp120 is associated with control of highly pathogenic chimeric SHIV(89.6P) replication in rhesus macaques. The vaccinated animal that had the highest titers of antibodies to the amino terminus portion of V1, prior to challenge, had secondary antibody responses that mediated cell killing by antibody-dependent cellular cytotoxicity (ADCC), as early as 2 weeks after infection and inhibited viral replication by antibody-dependent cell-mediated virus inhibition (ADCVI), by 4 weeks after infection. There was a significant inverse correlation between virus level and binding antibody titers to the envelope protein, (R=-0.83, p=0.015), and ADCVI (R=-0.84 p=0.044). Genotyping of plasma virus demonstrated in vivo selection of three SHIV(89.6P) variants with changes in potential N-linked glycosylation sites in V1. We found a significant inverse correlation between virus levels and titers of antibodies that mediated ADCVI against all the identified V1 virus variants. A significant inverse correlation was also found between neutralizing antibody titers to SHIV(89.6) and virus levels (R=-0.72 p=0.0050). However, passive inoculation of purified immunoglobulin from animal M316, the macaque that best controlled virus, to a naïve macaque, resulted in a low serum neutralizing antibodies and low ADCVI activity that failed to protect from SHIV(89.6P) challenge. Collectively, while our data suggest that anti-envelope antibodies with neutralizing and non-neutralizing Fc(R-dependent activities may be important in the control of SHIV replication, they also demonstrate that low levels of these antibodies alone are not sufficient to protect from infection.

Full Text

Duke Authors

Cited Authors

  • Bialuk, I; Whitney, S; Andresen, V; Florese, RH; Nacsa, J; Cecchinato, V; Valeri, VW; Heraud, J-M; Gordon, S; Parks, RW; Montefiori, DC; Venzon, D; Demberg, T; Guroff, MR; Landucci, G; Forthal, DN; Franchini, G

Published Date

  • December 9, 2011

Published In

Volume / Issue

  • 30 / 1

Start / End Page

  • 78 - 94

PubMed ID

  • 22037204

Pubmed Central ID

  • PMC3246802

Electronic International Standard Serial Number (EISSN)

  • 1873-2518

Digital Object Identifier (DOI)

  • 10.1016/j.vaccine.2011.10.040


  • eng

Conference Location

  • Netherlands