HIV-vaccines: lessons learned and the way forward

A safe and efficacious preventive HIV vaccine, as part of a comprehensive prevention program, remains among the highest public health priorities. It would be the best tool that could reduce the spread of HIV significantly in the long run. Current AIDS vaccine candidates are unable to induce neutralizing antibodies against primary HIV isolates or only to a very limited and narrow extent, representing a major obstacle in the development of an efficacious HIV vaccine. Clinical efforts have mainly focused on T-cell vaccines such as DNA and various recombinant vectors alone or in prime-boost regimens. The Merck Ad5 vaccine not only failed to show efficacy but also was associated with increased risk of HIV acquisition in vaccinees in a Phase IIb trial. While gp120 alone was not efficacious, the ALVAC prime and gp120 boost regimen showed 31% efficacy in a Phase III trial in Thailand. These contrasting results illustrate the limitations of available laboratory assays to assess the vaccine-induced immune responses and the lack of understanding of immune correlates of protection. Efforts should therefore focus on developing vaccine candidates inducing broadly neutralizing antibodies. Similarly, new vector strategies such as replicating vectors should be explored to induce strong and broad T-cell responses in the systemic and mucosal compartments. Innovation in immune assay development and testing algorithms is critically needed. The standardization of more relevant and predictive non-human primate models for immunogenicity and efficacy studies will contribute to better and faster vaccine assessment. HIV vaccine development requires innovative ideas and a sustained long-term commitment of the scientific community, civil society, politicians, and donors and participants for clinical research.