United States: Researchers at Massachusetts Institute of Technology (MIT) have made a significant advancement in HIV vaccine development, demonstrating that a two-dose shows a robust immune response.
The previous studies indicated that administering escalating doses of an HIV vaccine could boost the production of neutralizing antibodies. The team analyzed that a smaller first dose followed by a larger second dose, spaced one week apart, could achieve similar results.
Arup Chakraborty, John M. Deutch Institute Professor at MIT, highlighted the importance of integrating computational modeling with experimental data to optimize the vaccine schedule. Arup Chakraborty stated that, “By bringing together the physical and life sciences, we shed light on some basic immunological questions that helped develop this two-dose schedule.”
The study used an HIV envelope protein as the vaccine and combined it with a nanoparticle called SMNP, designed to enhance the B cell response. Although single-dose vaccines have been the norm in clinical trials, evidence suggests that a series of doses may be more effective in generating broadly neutralizing antibodies.
The research team, led by Sachin Bhagchandani PhD ’23 and Leerang Yang PhD ’24, explored various dosing strategies and discovered that delivering 20% of the vaccine in the first dose and 80% in the second produced a response on par with a seven-dose regimen. Their findings reveal that a small initial dose activates B cells, allowing them to respond more effectively when exposed to a larger amount of antigen in the second dose.
The two-dose schedule not only improved antibody responses by 60 times compared to a single dose but also enhanced T-cell responses by fivefold, showcasing the potential for this regimen in clinical applications.
Darrell Irvine, a senior author and former MIT professor now at the Scripps Research Institute, noted that , “Reducing the ‘escalating dose’ strategy down to two shots makes it much more practical for clinical implementation.”
The researchers are currently advancing this vaccine strategy in nonhuman primate models and exploring innovative materials that could extend the delivery of the second dose, further improving immune responses.
As HIV continues to infect over one million people globally each year, an effective vaccine could significantly curb the spread of the virus, particularly in regions where access to antiviral drugs is limited.
This pivotal research was funded by the Koch Institute Support Grant, the National Institutes of Health, and the Ragon Institute of MIT, MGH, and Harvard University.