Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates.
A primary goal of HIV-1 vaccine development is the consistent elicitation of protective, neutralizing antibodies. While highly similar neutralizing antibodies (nAbs) have been isolated from multiple HIV-infected individuals, it is unclear whether vaccination can consistently elicit highly similar nAbs in genetically diverse primates. Here, we show in three outbred rhesus macaques that immunization with Env elicits a genotypically and phenotypically conserved nAb response. From these vaccinated macaques, we isolated four antibody lineages that had commonalities in immunoglobulin variable, diversity, and joining gene segment usage. Atomic-level structures of the antigen binding fragments of the two most similar antibodies showed nearly identical paratopes. The Env binding modes of each of the four vaccine-induced nAbs were distinct from previously known monoclonal HIV-1 neutralizing antibodies, but were nearly identical to each other. The similarities of these antibodies show that the immune system in outbred primates can respond to HIV-1 Env vaccination with a similar structural and genotypic solution for recognizing a particular neutralizing epitope. These results support rational vaccine design for HIV-1 that aims to reproducibly elicit, in genetically diverse primates, nAbs with specific paratope structures capable of binding conserved epitopes.
Cai, Fangping, Wei-Hung Chen, Weimin Wu, Julia A. Jones, Misook Choe, Neelakshi Gohain, Xiaoying Shen, et al. “Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates.” Plos Pathog 17, no. 6 (June 2021): e1009624. https://doi.org/10.1371/journal.ppat.1009624.