National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01 AI145687
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
UM1 AI144371
米国
引用
ジャーナル: Cell / 年: 2024 タイトル: Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques. 著者: Kevin O Saunders / James Counts / Bhishem Thakur / Victoria Stalls / Robert Edwards / Kartik Manne / Xiaozhi Lu / Katayoun Mansouri / Yue Chen / Rob Parks / Maggie Barr / Laura Sutherland / ...著者: Kevin O Saunders / James Counts / Bhishem Thakur / Victoria Stalls / Robert Edwards / Kartik Manne / Xiaozhi Lu / Katayoun Mansouri / Yue Chen / Rob Parks / Maggie Barr / Laura Sutherland / Joena Bal / Nicholas Havill / Haiyan Chen / Emily Machiele / Nolan Jamieson / Bhavna Hora / Megan Kopp / Katarzyna Janowska / Kara Anasti / Chuancang Jiang / Elizabeth Van Itallie / Sravani Venkatayogi / Amanda Eaton / Rory Henderson / Christopher Barbosa / S Munir Alam / Sampa Santra / Drew Weissman / M Anthony Moody / Derek W Cain / Ying K Tam / Mark Lewis / Wilton B Williams / Kevin Wiehe / David C Montefiori / Priyamvada Acharya / Barton F Haynes / 要旨: The CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs ...The CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs for many reasons, including the occlusion of CD4bs by glycans, expansion of appropriate naive B cells with immunogens, and selection of functional antibody mutations. Here, we demonstrate that immunization of macaques with a CD4bs-targeting immunogen elicits neutralizing bnAb precursors with structural and genetic features of CD4-mimicking bnAbs. Structures of the CD4bs nAb bound to HIV-1 Env demonstrated binding angles and heavy-chain interactions characteristic of all known human CD4-mimicking bnAbs. Macaque nAb were derived from variable and joining gene segments orthologous to the genes of human VH1-46-class bnAb. This vaccine study initiated in primates the B cells from which CD4bs bnAbs can derive, accomplishing the key first step in the development of an effective HIV-1 vaccine.