title: Putative rhesus macaque germline predecessors of human broadly HIV-neutralizing antibodies: differences from the human counterparts and implications for HIV-1 vaccine development.
abstract: Broadly neutralizing antibodies (bnAbs) are likely to be a key component of protective immunity conferred by an effective HIV-1 vaccine. We and others have reported that putative human germline predecessors of known human bnAbs lack measurable binding to HIV-1 envelope glycoproteins (Env), which could be a new challenge for eliciting human bnAbs. Rhesus macaques have been used as nonhuman primate models for testing vaccine candidates, but little is known about their germline Abs. Here we show the similarities and differences between putative rhesus macaque and human germline predecessors and possible intermediate antibodies of one of the best characterized bnAbs, b12. Similar to the human counterpart, a putative rhesus macaque b12 germline antibody lacks measurable binding to HIV-1 Envs, suggesting that initiation of somatic maturation of rhesus macaque germline b12 predecessor may also be a challenge. However, differences in sequence characteristics and binding properties between macaque and human b12 germline and intermediate antibodies suggest that the two germline predecessors may undergo different maturation pathways in rhesus macaques and in humans. These results indicate that immunogens that could initiate the immune responses and drive somatic mutations leading to elicitation of b12 or b12-like bnAbs in rhesus macaques and in humans are likely to be different. This has important implications for HIV-1 vaccine development.
authors.affiliation: AIDS Institute, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Yuan
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.forename: Emily
authors.initials: E
authors.lastname: Streaker
authors.forename: Dimiter S
authors.initials: DS
authors.lastname: Dimitrov
authors.forename: Mei-Yun
authors.initials: MY
authors.lastname: Zhang
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D002461:Cell Line, Transformed; D018095:Germ-Line Mutation / Q000276:immunology*; D057809:HEK293 Cells; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008253:Macaca mulatta; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus