May 18th marks HIV Vaccine Awareness Day (HVAD). This day is an opportunity to reflect on the work which is currently being done in all areas of the community to find a safe and effective vaccine against HIV.
HIV Vaccine Day was born from a speech given by Bill Clinton in 1997 in which he stated that “only a truly effective, preventive HIV vaccine can limit and eventually eliminate the threat of AIDS.” Scientists have certainly come a long way since then, but it seems they still have much further to go to complete this colossal task.
The development of a vaccine against HIV-1 infection remains a significant global challenge. It is particularly difficult to develop a vaccine for HIV due to its huge antigenic variation, and the specialised mechanisms it employs to escape the human immune system.
HIV vaccine research is evolving rapidly, and Retrovirology has recently published some interesting articles contributing to the field.
Broadly neutralising antibodies (bNAbs) are one of the main focuses of HIV vaccine research. These antibodies are capable of binding to proteins on the viral envelope, the Env complex, a trimer of gp120/gp41 heterodimers. The bNAbs binding prevents Env from binding with cell surface receptors and consequently entering the cell. The challenge is encouraging the body to make the antibodies naturally, and to do this we must mimic the Env complex which the antibody will bind to.
In a research article recently published in Retrovirology, Nancy Chung and colleagues created cell lines which express an engineered stable HIV-1 envelope glycoprotein trimer (BG505 SOSIP.664 gp140), which mimics the Env complex, to which antibodies can bind. The authors conclude that the trimers produced by the cell lines had the same native-like appearance as those derived by transient HIV transfection, and appropriate antigenic properties for antibodies to bind to. The cell lines yielded proteins of an appropriate quality for structural studies, animal immunogenicity experiments, and potentially for human clinical trials. This basic research may enable the development of these trimers for vaccine production in the future.
An important target for HIV neutralising antibodies is the CD4 binding site of Env gp120. However, some strains of HIV, including CRF01_AE viruses are resistant to neutralization mediated by these antibodies. A recent article by Piraporn Utachee and colleagues investigates this underlying resistance and identifies the two regions of gp120 that contain the major determinants of viral resistance to neutralising antibodies. The regulatory mechanisms underlying the susceptibilities of various HIV-1 strains to neutralising antibodies is extremely important to understand for vaccine development.
Developing a safe and effective vaccine against HIV is hugely important for preventing the transmission of the disease. An HIV vaccine could arguably be the best and most cost-effective way of controlling the disease, and is particularly important for those whom other interventions are not sufficiently effective for or available.