Learned young: HIV-1 germline-targeting vaccination in infants

It is standard practice to protect infants against viruses that they are exposed to early in life, during childhood, or as adults. While HIV-1 is only rarely a risk in the period between the end of breast-feeding and the onset of sexual maturity, there are good immunological and practical arguments for assessing whether vaccination of young children might be beneficial.

Studies of HIV-1-infected individuals suggest that the characteristics of the developing immune system may favor the evolution of B cells that produce broadly neutralizing antibodies (bNAbs), when compared to the same processes in adults. One way to exploit these properties of the infant immune system is targeting the germline precursors of B cells that can, over time and with the right sequential antigenic stimuli, mature into bNAb-producing plasma cells. Multidose immunization over time is standard practice within global childhood vaccine frameworks.

We discuss strategies to accomplish the goal of inducing bNAbs, based on the use of specifically designed envelope glycoprotein immunogens. We also summarize how bNAbs may be used for passive protection of infants and combined with active vaccination.