HIV‐1 neutralizing antibodies: understanding nature's pathways

Summary The development of an effective vaccine has been hindered by the enormous diversity of human immunodeficiency virus‐1 ( HIV ‐1) and its ability to escape a myriad of host immune responses. In addition, conserved vulnerable regions on the HIV ‐1 envelope glycoprotein are often poorly immunogenic and elicit broadly neutralizing antibody responses ( BNA bs) in a minority of HIV ‐1‐infected individuals and only after several years of infection. All of the known BNA bs demonstrate high levels of somatic mutations and often display other unusual traits, such as a long heavy chain complementarity determining region 3 ( CDRH 3) and autoreactivity that can be limited by host tolerance controls. Nonetheless, the demonstration that HIV ‐1‐infected individuals can make potent BNA bs is encouraging, and recent progress in isolating such antibodies and mapping their immune pathways of development is providing new strategies for vaccination.