Strategies to guide the antibody affinity maturation process

•Broadly neutralizing HIV-1 and influenza antibodies possess significant levels of affinity maturation.•Choice of initial immunogens may be critical to select naïve B cells that can mature appropriately.•Viral diversity leads to development of broadly neutralizing antibodies.•HIV-1 and influenza immunogen design breakthroughs.•Antibody-virus co-evolution studies in HIV-1 and influenza infections suggest immunization strategies.

Antibodies with protective activity are critical for vaccine efficacy. Affinity maturation increases antibody activity through multiple rounds of somatic hypermutation and selection in the germinal center. Identification of HIV-1 specific and influenza-specific antibody developmental pathways, as well as characterization of B cell and virus co-evolution in patients, has informed our understanding of antibody development. In order to counteract HIV-1 and influenza viral diversity, broadly neutralizing antibodies precisely target specific sites of vulnerability and require high levels of affinity maturation. We present immunization strategies that attempt to recapitulate these natural processes and guide the affinity maturation process.