Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide a blueprint for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. The mature antibody, CH103, neutralized approximately 55% of HIV-1 isolates, and its co-crystal structure with the HIV-1 envelope protein gp120 revealed a new loop-based mechanism of CD4-binding-site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the unmutated common ancestor of the CH103 lineage avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data determine the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies, and provide insights into strategies to elicit similar antibodies by vaccination.

Frequent recombination and strong purifying selection facilitate the cross-species transmission of coronaviruses to humans.

An unconventional route to protection: One promising approach toward an HIV-1 vaccine involves infecting people with cytomegalovirus engineered to express proteins from HIV-1. This approach, which works by eliciting virus-killing CD8 ⁺ T cells, provides robust protection in nonhuman primate models. Hansen et al. have found out why this approach is so effective. Normally, peptide antigens presented by major histocompatibility complex-1a (MHC-Ia) activate CD8 ⁺ T cells. In vaccinated monkeys, however, CD8 ⁺ T cells reacted to peptide antigens presented by MHC-E molecules instead. Moreover, MHC-E could present a much wider range of peptides than MHC-Ia. Science , this issue p. 714