A groundbreaking HIV vaccine candidate developed by the Duke Human Vaccine Institute has demonstrated the ability to stimulate low levels of a crucial type of broadly neutralising HIV antibodies in participants of a 2019 clinical trial.
This significant finding, published on May 17 in the journal Cell, not only validates the vaccine's capacity to induce these antibodies, which are pivotal in combating diverse strains of HIV, but also highlights its ability to initiate this process within a matter of weeks, thus initiating a vital immune response.
The vaccine candidate targets a specific area on the HIV-1 outer envelope known as the membrane proximal external region (MPER), which stays relatively stable despite the virus's mutations. Antibodies directed against this region of the virus's outer coat have the potential to block infection by numerous circulating strains of HIV. According to senior author Barton F Haynes, MD, director of the Duke Human Vaccine Institute, this breakthrough represents a significant advancement in HIV vaccine research. He emphasises that while the induction of neutralising antibodies against the most challenging strains of HIV is promising, the ultimate goal is to elicit even more potent neutralising antibodies against other vulnerable sites on the virus to prevent viral escape.
The study, which analysed data from a phase 1 clinical trial, involved twenty healthy, HIV-negative participants. After just two immunisations with the investigational vaccine, a remarkable 95% serum response rate and a 100% blood CD4+ T-cell response rate was observed, indicating robust immune activation. Importantly, the vaccine induced broadly neutralising antibodies after just two doses, a feat that typically takes several years post-infection to achieve. Despite the trial being halted due to a participant experiencing a non-life-threatening allergic reaction, the researchers remain optimistic about the vaccine’s potential.
Lead author, Dr Wilton Williams, underscores the challenge of recreating the complex series of events necessary to induce broadly neutralising antibodies within a shorter timeframe using a vaccine. However, he notes the excitement of witnessing the emergence of neutralising antibodies within weeks of vaccination, thanks to this vaccine molecule. The researchers acknowledge that further work is needed to enhance the vaccine’s effectiveness and target additional regions of the virus envelope. They envision a successful HIV vaccine consisting of multiple components aimed at vulnerable sites on the virus envelope to prevent
viral escape.
Conclusion
This study demonstrates the feasibility of inducing broadly neutralising antibodies in humans through vaccination. With this knowledge, researchers are poised to replicate and build upon these findings, paving the way for the development of a highly effective HIV vaccine that could transform the landscape of HIV prevention and treatment.
Reference:
Williams WB, Alam SM, Ofek G, et al. Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans. Cell, 2024; DOI: 10.1016/j.cell.2024.04.033.
