Partial efficacy of a broadly neutralizing antibody against cell-associated SHIV infection.

Published

Journal Article

Broadly neutralizing antibodies (BnAbs) protect macaques from cell-free simian/human immunodeficiency virus (SHIV) challenge, but their efficacy against cell-associated SHIV is unclear. Virus in cell-associated format is highly infectious, present in transmission-competent bodily fluids, and potentially capable of evading antibody-mediated neutralization. The PGT121 BnAb, which recognizes an epitope consisting of the V3 loop and envelope glycans, mediates antibody-dependent cellular cytotoxicity and neutralization of cell-to-cell HIV-1 transmission. To evaluate whether a BnAb can prevent infection after cell-associated viral challenge, we infused pigtail macaques with PGT121 or an isotype control and challenged animals 1 hour later intravenously with SHIVSF162P3-infected splenocytes. All five controls had high viremia 1 week after challenge. Three of six PGT121-infused animals were completely protected, two of six animals had a 1-week delay in onset of high viremia, and one animal had a 7-week delay in onset of viremia. The infused antibody had decayed on average to 2.0 μg/ml by 1 week after infusion and was well below 1 μg/ml (range, <0.1 to 0.8 μg/ml) by 8 weeks. The animals with a 1-week delay before high viremia had relatively lower plasma concentrations of PGT121. Transfer of 22 million peripheral blood mononuclear cells (PBMCs) stored at weeks 1 to 4 from the animal with the 7-week delayed onset of viremia into uninfected macaques did not initiate infection. Our results show that HIV-1-specific neutralizing antibodies have partial efficacy against cell-associated virus exposure in macaques. We conclude that sustaining high concentrations of bioavailable BnAb is important for protecting against cell-associated virus.

Full Text

Duke Authors

Cited Authors

  • Parsons, MS; Lloyd, SB; Lee, WS; Kristensen, AB; Amarasena, T; Center, RJ; Keele, BF; Lifson, JD; LaBranche, CC; Montefiori, D; Wines, BD; Hogarth, PM; Swiderek, KM; Venturi, V; Davenport, MP; Kent, SJ

Published Date

  • August 9, 2017

Published In

Volume / Issue

  • 9 / 402

PubMed ID

  • 28794282

Pubmed Central ID

  • 28794282

Electronic International Standard Serial Number (EISSN)

  • 1946-6242

Digital Object Identifier (DOI)

  • 10.1126/scitranslmed.aaf1483

Language

  • eng

Conference Location

  • United States