HIV vaccine development and broadly neutralizing antibodies

Human immunodeciency virus-1 (HIV-1)infects about 35 million people worldwide[1]. There is no vaccine in current clinicaluse. Although available drug treatmentsare generally effective in controlling infec-tion, they are not curative, can cause signi-cant side effects and are unable to preventcomorbidities such as cardiovascular dis-easeand cancers. In2012,about 1.6millionpeople worldwide died from acquired im-munodeciencysyndromeduetoHIVinfec-tion [1]. Therefore, there is global interest indeveloping an effective vaccine.HIV-1 evolves extremely rapidly due to thelow delity of the virus reverse transcriptase.So,althoughmostHIV-1infectionsstartwitha single virion, within a year, the HIV-1viruses in one infected individual can exhibitabout the same amount of genetic variationasisdisplayedbyinuenzaAvirusesgloballyover the course of a year [ 2]. Neutralizingantibodies can drive variation of HIV enve-lope proteins, which in turn selects for vari-ation in antibody structure, i.e. co-evolution[3](Figure 1). Therefore, strong protectionmight only be associated with vaccineimmunogens capable of eliciting potent,broadly neutralizing antibodies (pbnAbs),which inactivate a very substantial fractionof HIVviruses. PbnAbs often carry anunusu-allyhighnumberofsomaticmutationsintheassociated antigen-bi nding domains (vari-able or V domains) [4] and can also possessother unusual features, such as unusuallylong heavy chain third hypervariable regions,the most variable portion of the V domains.