Lessons learned from humoral responses of HIV patients

Since 2009 many broadly neutralizing antibodies against HIV have been identified, yet there is still no vaccine capable of inducing such antibodies in humans. This review considers the early observations of HIV sera neutralization in light of more recent studies and highlights areas for future research.

Large clinical cohort studies using standardized neutralization assays and pseudoviruses derived from primary isolates have shown that 10-30% of HIV infections result in some level of serum neutralization breadth. However, less than 10% of individuals develop a greater breadth of neutralization and are termed elite neutralizers.

During HIV infection, many individuals develop strain-specific neutralization against their viral quasispecies, and similar immunogen-matched activity can now be induced in animal models. However, only in a minority of infections do broadly neutralizing antibodies develop. Therefore, understanding how the viral diversity, host immune environment, and antibody repertoires intersect to support the generation of neutralization breadth in elite neutralizers could provide guidelines as to how to improve immunization responses.