PT - JOURNAL ARTICLE AU - Bartek Nogal AU - Matteo Bianchi AU - Christopher A. Cottrell AU - Robert N. Kirchdoerfer AU - Leigh M. Sewall AU - Hannah L. Turner AU - Fangzhu Zhao AU - Devin Sok AU - Dennis R. Burton AU - Lars Hangartner AU - Andrew B. Ward TI - Mapping polyclonal antibody responses in non-human primates vaccinated with HIV Env trimer subunit vaccines AID - 10.1101/833715 DP - 2019 Jan 01 TA - bioRxiv PG - 833715 4099 - http://biorxiv.org/content/early/2019/11/07/833715.short 4100 - http://biorxiv.org/content/early/2019/11/07/833715.full AB - 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.