Todd Bradley, Masayuki Kuraoka, Chen-Hao Yeh, Ming Tian, Huan Chen, Derek W Cain, Xuejun Chen, Cheng Cheng, Ali H Ellebedy, Robert Parks, Maggie Barr, Laura L Sutherland, Richard M Scearce, Cindy M Bowman, Hilary Bouton-Verville, Sampa Santra, Kevin Wiehe, Mark G Lewis, Ane Ogbe, Persephone Borrow, David Montefiori, Mattia Bonsignori, M Anthony Moody, Laurent Verkoczy, Kevin O Saunders, Rafi Ahmed, John R Mascola, Garnett Kelsoe, Frederick W Alt, Barton F Haynes
Eliciting protective titers of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but current vaccine strategies have yet to induce bnAbs in humans. Many bnAbs isolated from HIV-1-infected individuals are encoded by immunoglobulin gene rearrangments with infrequent naive B cell precursors and with unusual genetic features that may be subject to host regulatory control. Here, we administer antibodies targeting immune cell regulatory receptors CTLA-4, PD-1 or OX40 along with HIV envelope (Env) vaccines to rhesus macaques and bnAb immunoglobulin knock-in (KI) mice expressing diverse precursors of CD4 binding site HIV-1 bnAbs...
February 19, 2020: Nature Communications