Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization.
The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be elicited, we identified, characterized, and tracked five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) in vaccinated macaques over time. Genetic and structural analyses revealed two of these lineages to belong to a reproducible class capable of neutralizing up to 59% of 208 diverse viral strains. B cell analysis indicated each of the five lineages to have been initiated and expanded by FP-carrier priming, with envelope (Env)-trimer boosts inducing cross-reactive neutralization. These Abs had binding-energy hotspots focused on FP, whereas several FP-directed Abs induced by immunization with Env trimer-only were less FP-focused and less broadly neutralizing. Priming with a conserved subregion, such as FP, can thus induce Abs with binding-energy hotspots coincident with the target subregion and capable of broad neutralization.
Kong, R; Duan, H; Sheng, Z; Xu, K; Acharya, P; Chen, X; Cheng, C; Dingens, AS; Gorman, J; Sastry, M; Shen, C-H; Zhang, B; Zhou, T; Chuang, G-Y; Chao, CW; Gu, Y; Jafari, AJ; Louder, MK; O'Dell, S; Rowshan, AP; Viox, EG; Wang, Y; Choi, CW; Corcoran, MM; Corrigan, AR; Dandey, VP; Eng, ET; Geng, H; Foulds, KE; Guo, Y; Kwon, YD; Lin, B; Liu, K; Mason, RD; Nason, MC; Ohr, TY; Ou, L; Rawi, R; Sarfo, EK; Schön, A; Todd, JP; Wang, S; Wei, H; Wu, W; NISC Comparative Sequencing Program, ; Mullikin, JC; Bailer, RT; Doria-Rose, NA; Karlsson Hedestam, GB; Scorpio, DG; Overbaugh, J; Bloom, JD; Carragher, B; Potter, CS; Shapiro, L; Kwong, PD; Mascola, JR
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