The road to an HIV vaccine

Abstract

Acquired Immunodeciency Syndrome (AIDS) and its etiological agent Human Immunodeficiency Virus (HIV) have caused a global pandemic for which an comprehensive elimination strategy remains elusive. Treatment, which does not clear HIV infection, but rather delays the progression to AIDS, remains economically and socially inaccessible in the places where the burden of disease is greatest, and to date, no vaccine has been developed. Thus, there is some question about how to end the AIDS pandemic. Here, we develop a compartmental epidemiological model for HIV and show that 1) a highly efficacious vaccine would be more effective in reducing incidence and prevalence of disease than aggressive treatment, and 2) a partially efficacious vaccine can also be highly effective if coverage is high. While previous attempts to develop a vaccine have failed, the discovery of broadly neutralizing antibodies in a number of infected individuals as well as the characterization of the viral epitopes these antibodies target has renewed hopes for a vaccine. Here, we demonstrate that variable loop 3 (V3) on the outer domain of the HIV surface protein presents a potentially attractive template for vaccine design. Furthermore, we present a conserved specificity for antibody mediated neutralization at the V epitope that is dependent on two glycans. The ability of broadly neutralizing antibodies to instruct the development of a HIV vaccine would validate the paradigm of rational vaccine design and fundamentally alter the way in which we approach vaccines to present and future diseases.