Role of neutralizing antibodies in protective immunity against HIV.

HIV continues to be a major health problem world wide, however the situation is particularly serious in Asian and Sub-Saharan countries. Therefore, development of an effective HIV vaccine could help to reduce the severity of the disease and prevent infection. Over the last two decades significant efforts have been made towards inducing potent humoral and cellular immune responses by vaccination, however antibodies and CTL responses alone are likely not sufficient for inducing sterilizing immunity or long-term control of viral replication. Therefore, it is generally believed that both humoral and cellular responses will be needed for an effective HIV vaccine. In support of humoral immunity, monoclonal antibodies that recognize critical neutralizing epitopes have shown to be effective at passive transfer experiments in conferring protection against challenge infection. However, antibodies to similar epitope specificities are difficult to induce by vaccination. Therefore, optimization of Env structure is needed for exposing appropriate neutralizing epitopes and masking non-neutralizing epitopes. Since the crystal structure of the core of Env glycoprotein has been solved, efforts are in progress to design novel Env immunogens that may induce effective neutralizing responses. Furthermore, there are HIV-1 strains that are resistant to neutralization by monoclonal antibodies, yet neutralized by pooled sera from HIV-1 patients. Therefore, efforts should be made to identify these novel epitopes and to design strategies to incorporate them in potential vaccines. To facilitate comparative evaluation of vaccine immunogens for their ability to induce cross clade neutralizing antibodies, efforts should be made to use standardized neutralization assays and standard virus panels. Once potent HIV Env structure have been identified, their effectiveness may be enhanced through the use of adjuvants, delivery systems and prime and boost strategies to improve the quality and magnitude of neutralizing responses.