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Mapping polyclonal antibody responses in non-human primates vaccinated with HIV Env trimer subunit vaccines

By Bartek Nogal, Matteo Bianchi, Christopher Cottrell, Robert N. Kirchdoerfer, Leigh M. Sewall, Hannah L Turner, Fangzhu Zhao, Devin Sok, Dennis R. Burton, Lars Hangartner, Andrew Ward

Posted 07 Nov 2019
bioRxiv DOI: 10.1101/833715 (published DOI: 10.1016/j.celrep.2020.02.061)

Rational immunogen design aims to focus antibody responses to vulnerable sites on the primary antigens. Given the size of these antigens there is however potential for eliciting unwanted, off-target responses. Here, we used our electron microscopy polyclonal epitope mapping approach to describe the antibody specificities elicited by immunization of non-human primates with soluble HIV envelope trimers and subsequent repeated viral challenge. An increased diversity of epitopes recognized, and the approach angle by which these antibodies bound, constituted a hallmark of the humoral response in most protected animals. We also show that fusion peptide-specific antibodies are responsible for some neutralization breadth. Moreover, cryoEM analysis of a fully-protected animal revealed a high degree of clonality within a subset of putatively neutralizing antibodies, enabling a detailed molecular description of the antibody paratope. Our results provide important insights into the immune response against a vaccine candidate that entered into clinical trials earlier this year.

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