National Institutes of Health/National Human Genome Research Institute
AI136621
米国
National Institutes of Health/National Human Genome Research Institute
AI100663
米国
引用
ジャーナル: Cell Rep / 年: 2020 タイトル: Mapping Polyclonal Antibody Responses in Non-human Primates Vaccinated with HIV Env Trimer Subunit Vaccines. 著者: Bartek Nogal / Matteo Bianchi / Christopher A Cottrell / Robert N Kirchdoerfer / Leigh M Sewall / Hannah L Turner / Fangzhu Zhao / Devin Sok / Dennis R Burton / Lars Hangartner / Andrew B Ward / 要旨: Rational immunogen design aims to focus antibody responses to vulnerable sites on primary antigens. Given the size of these antigens, there is, however, potential for eliciting unwanted, off-target ...Rational immunogen design aims to focus antibody responses to vulnerable sites on primary antigens. Given the size of these antigens, there is, however, potential for eliciting unwanted, off-target responses. Here, we use 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 bind constitute a hallmark of the humoral response in most protected animals. We also show that fusion peptide-specific antibodies are likely responsible for some neutralization breadth. Moreover, cryoelectron microscopy (cryo-EM) analysis of a fully protected animal reveals 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 in 2019.