Neutralizing antibody responses to HIV: role in protective immunity and challenges for vaccine design

AIDS continues to be a major health problem throughout the world with a high degree of mortality and morbidity. Therefore, there is an urgent need for an effective anti-HIV vaccine. Although the correlates of protective immunity against infection by HIV remain unidentified, recent studies have demonstrated that both humoral and cellular responses are required for controlling viral replication. Vaccine efforts should therefore aim at developing broad and potent humoral as well as cellular responses. Anti-HIV T-cell responses can be generated both in animals and humans by several vaccine modalities. In contrast, broadly neutralizing antibody responses against HIV have not been elicited by any strategy tested in the clinic thus far. The presence of such responses has the potential to prevent the establishment of infection. If not, the presence of neutralizing antibodies may significantly reduce the number of cells that become infected, therefore reducing the inoculum, which may delay viral spread and allow for a better control of viral replication in the infected host. Finally, cytotoxic T-lymphocytes may facilitate the clearance of virally infected cells. One of the biggest challenges in HIV vaccine development is to design a HIV envelope immunogen that can induce protective neutralizing antibodies effective against the diverse HIV-1 strains that characterize the global pandemic. The focus of this article is to review the importance of antibodies and the strategies that are currently being used for inducing such antibodies.