Non-neutralizing antibodies in prevention of HIV infection

Introduction: One of the challenges facing the development of an AIDS vaccine is eliciting antibody (Ab) capable of preventing the acquisition of HIV. Broadly neutralizing Ab (bnAb) that can prevent HIV infection has proven to be difficult to elicit. Here, we consider the potential for protective non-neutralizing Ab (pnnAb) to provide the much needed Ab component for an HIV vaccine. Such Ab acts by tagging virus or infected cells for destruction by the innate immune system. Areas covered: We review interactions between the Fc region of immunoglobulin G (IgG) and Fc Upsilon receptors or complement that can lead to the destruction of HIV or HIV-infected cells, correlations between the presence of pnnAb and the prevention of HIV and simian immunodeficiency virus (SIV) infections, differences between classical HIV-specific bnAb and HIV-specific pnnAb, HIV envelope antigens and adjuvants which have been hypothesized to generate pnnAb, and the use of avidity as a serological correlate for pnnAb. Expert opinion: We hypothesize that selection of HIV for the poor ability to elicit bnAb has also selected it for slow entry into cells and a window of opportunity for pnnAb to tag virus for destruction by innate immune responses.