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

Partial efficacy of a broadly neutralizing antibody against cell-associated SHIV infection.
Author Information (click to view)

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,


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, (click to view)

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,

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Science translational medicine 9(402) pii 10.1126/scitranslmed.aaf1483

Abstract

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.

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