Human immunodeficiency virus and antibodies: Catch 22

A potent HIV vaccine is a need of the hour, to prevent HIV-1 infection and end the global pandemic. For the past 30years or more than that, tremendous research is being carried out in the field of vaccine studies in plotting an apt design/template for an ideal HIV-1 vaccine, its formulation, and its delivery routes. Unfortunately, the long-established vaccine methodologies have failed so far in developing an effective HIV-1 vaccine. To tackle the situation, researchers worked toward gaining an insight into the biology and immunology of HIV-1 infection, and its infection-pathway studies, giving impetus to studies on the properties of circulating viruses during natural infection and the evolving antibody responses in the host. The resulting studies have brought about the concept of “elite neutralizers” and the associated virological and immunological parameters, contributing to the development of broad and potent neutralizing antibodies in such rare HIV-1-infected individuals (termed elite neutralizers) that prevent disease progression. Broadly neutralizing antibodies (bnAbs) have been found in a limited number of HIV-1-infected adult individuals and evolve after at least 3-4years post-infection. Such candidates can be the elite neutralizers who possess very potential and bnAbs within them. Therefore, the chapter delineates parameters that lead to the formation of bnAbs during normal virus infection. The so-called factors involved are the identification of various epitopes of the virus and its binding sites with the bnAb/precursors, how the virus (envelope) escapes the bnAb activity by evolving multiple evasion strategies which are accredited to the different patterns of the envelope protein. Recent studies have shown the development of bnAbs in HIV-1-infected infants. The identification and importance of pediatric nAbs have been extensively studied and reviewed herein. Furthermore, a note on the elucidation pathways of nAbs for achieving a better neutralization breadth and how the viral diversity or strains influences the selection of bnAbs are also mentioned. The plausibility of employing potent bnAbs for passive immunization via its individual or combinatorial administration and a glimpse of the ongoing clinical trials of bnAbs has been discussed.