Protection against a mixed SHIV challenge by a broadly neutralizing antibody cocktail.

Abstract

HIV-1 sequence diversity presents a major challenge for the clinical development of broadly neutralizing antibodies (bNAbs) for both therapy and prevention. Sequence variation in critical bNAb epitopes has been observed in most HIV-1-infected individuals and can lead to viral escape after bNAb monotherapy in humans. We show that viral sequence diversity can limit both the therapeutic and prophylactic efficacy of bNAbs in rhesus monkeys. We first demonstrate that monotherapy with the V3 glycan-dependent antibody 10-1074, but not PGT121, results in rapid selection of preexisting viral variants containing N332/S334 escape mutations and loss of therapeutic efficacy in simian-HIV (SHIV)-SF162P3-infected rhesus monkeys. We then show that the V3 glycan-dependent antibody PGT121 alone and the V2 glycan-dependent antibody PGDM1400 alone both fail to protect against a mixed challenge with SHIV-SF162P3 and SHIV-325c. In contrast, the combination of both bNAbs provides 100% protection against this mixed SHIV challenge. These data reveal that single bNAbs efficiently select resistant viruses from a diverse challenge swarm to establish infection, demonstrating the importance of bNAb cocktails for HIV-1 prevention.

DOI: 10.1126/scitranslmed.aao4235

Cite this paper

@article{Julg2017ProtectionAA, title={Protection against a mixed SHIV challenge by a broadly neutralizing antibody cocktail.}, author={Boris Julg and Po-Ting Liu and Kshitij Wagh and William M Fischer and Peter Abbink and Noe B Mercado and James Whitney and Joseph P. Nkolola and Katherine McMahan and Lawrence J Tartaglia and Erica N. Borducchi and Shreeya Khatiwada and Megha Kamath and Jake A LeSuer and Michael S. Seaman and Stephen D Schmidt and John R. Mascola and Dennis R. Burton and Bette T. Korber and Dan H Barouch}, journal={Science translational medicine}, year={2017}, volume={9 408} }