title: Targeting B-cell germlines and focusing affinity maturation: the next hurdles in HIV-1-vaccine development?
abstract: Vaccines that protect against viral infection usually elicit neutralizing antibodies, but HIV-1 vaccine candidates have failed to induce broad and potent such responses. Broadly active neutralizing antibodies (bNAbs) do, however, slowly emerge in a minority of HIV-1-infected subjects; and passive immunization with bNAbs protects against viral acquisition in animal models of HIV-1 infection. New techniques have made it possible to interrogate human B cells and thereby to isolate highly potent bNAbs to uncharted epitope clusters. Furthermore, recent high-resolution structure determinations of near-native soluble envelope glycoprotein trimers in complex with different bNAbs reveal the molecular basis for neutralization. Such trimer structures may serve as blueprints for vaccine design. Here we discuss how a vaccine might bridge a reactivity gap from germline antibody to bNAb and simulate the intricate stimuli of affinity maturation that sometimes prevail in chronic infection.
authors.forename: Max
authors.initials: M
authors.lastname: Medina-Ramírez
authors.forename: Rogier W
authors.initials: RW
authors.lastname: Sanders
authors.forename: Per Johan
authors.initials: PJ
authors.lastname: Klasse
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology* / Q000302:isolation & purification*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control* / Q000628:therapy; D015497:HIV-1 / Q000276:immunology*; D006801:Humans
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies