Developing an effective HIV vaccine has long been a formidable challenge, primarily due to the virus’s rapid mutation rates, which enable it to evade the immune response generated by traditional vaccines.
However, groundbreaking research from MIT offers a promising solution: a two-dose vaccination schedule that might be just as effective as much longer vaccination regimens.
Previously, MIT researchers had demonstrated that administering escalating doses of an HIV vaccine over a two-week period could generate larger quantities of neutralizing antibodies.
This method, however, is impractical for mass vaccination campaigns due to its complexity.
In a new study combining computational modeling and animal experiments, researchers have now found that a similar immune response can be achieved with just two doses administered one week apart.
The initial smaller dose primes the immune system to respond more powerfully to the subsequent larger dose.
The study employed an HIV envelope protein and showed promising results.
A single-dose version of the vaccine is already in clinical trials, and the team hopes to initiate trials with the new two-dose schedule soon.
“By integrating the physical and life sciences, we’ve answered basic immunological questions that helped us develop this two-dose regimen to mimic the multi-dose approach,” said Arup Chakraborty, the John M. Deutch Institute Professor at MIT.
This approach could potentially be adapted to vaccines for other diseases as well.
Each year, HIV infects over 1 million people globally, many of whom do not have access to antiviral drugs. An effective vaccine could be a game-changer for preventing these infections.
One promising candidate now in clinical trials consists of an HIV protein called an envelope trimer and a nanoparticle known as SMNP.
The nanoparticle, developed by Darrell Irvine’s lab, enhances the B cell response to the vaccine.
Clinical trials have shown that a series of doses is more effective than a single dose in generating broadly neutralizing antibodies.
The seven-dose regimen is believed to work well because it mimics the body’s natural response to virus exposure, where more viral proteins accumulate, spurring the immune system to mount a stronger defense.
In the recent MIT study, the team compared the immune responses generated by various dosing schedules, ranging from one to seven doses over 12 days.
While three or more doses produced strong antibody responses, two doses initially did not.
By adjusting the dose intervals and ratios, they discovered that administering 20% of the total vaccine in the first dose and the remaining 80% in the second dose, spaced seven days apart, achieved results similar to the seven-dose regimen.
Using computational models, researchers found that when a single dose is administered, most of the antigen gets degraded before reaching the lymph nodes, where B cells are activated.
In contrast, a small initial dose ensures that some B cells and antibodies develop, preparing the immune system for a more robust response to the larger second dose.
Moreover, the two-dose regimen induces a stronger T-cell response. The initial dose activates dendritic cells, which promotes inflammation and T-cell activation.
When the second dose is administered, it boosts this response further, leading to a fivefold increase in T-cell response and a 60-fold increase in antibody response compared to a single dose.
“Condensing the ‘escalating dose’ strategy to just two shots makes it far more feasible for clinical implementation,” said Irvine.
The researchers are also exploring technologies that could deliver the second dose over an extended period, which might further enhance the immune response and make the vaccine more practical for mass vaccinations.
Future studies are planned to test this two-dose strategy in a nonhuman primate model.
Grants from the Koch Institute, the National Cancer Institute, the National Institutes of Health, and the Ragon Institute of MIT, MGH, and Harvard funded the research.