Developing an effective HIV vaccine is a research priority, but it has been difficult, partly because vaccines have not been able to generate sufficient antiviral immunity to prevent infection or quickly control infection. With his new grant funded by the National Institutes of Health, Pablo Penaloza-MacMaster, PhD, will conduct innovative research to examine whether giving a smaller initial dose of an HIV vaccine can make it work better in the long run.

“Results from our prior research suggest that administering a smaller initial dose of viral vector vaccines improves the long-term effectiveness of vaccines, which could be important not just for HIV but also for other diseases like COVID-19 and influenza,” said Penaloza-MacMaster, an associate professor of microbiology-immunology at Northwestern University Feinberg School of Medicine and a TC CFAR faculty member. “In our new study, we plan to extend these results to mRNA vaccines.”

The clinical testing of HIV vaccine candidates involves dose-escalation studies comparing a variety of vaccine doses in individuals who receive the same dose of the vaccine during the prime and the boost. However, HIV vaccine trials do not usually evaluate “intragroup dose escalation,” in which people would first get a prime with a low dose and then a boost with a higher dose, according to Penaloza-MacMaster. His new research will investigate “intragroup dose escalation,” with the goal of eventually adding to HIV vaccine options and ending the HIV epidemic.

“We hope that our studies will elucidate ways in which vaccine immunity could be improved, resulting in not only greater, but also more durable, immune responses to HIV,” said Penaloza-MacMaster. “We are excited about these findings, but more studies are needed to determine whether the research will lead to the development of an effective HIV vaccine.”

Penaloza-MacMaster was the recipient of a TC CFAR Basic Science Collaborative Innovation Award and received support from the Center that was essential for his new research grant.

“The support from the TC CFAR has been invaluable, enabling us to collect the preliminary data needed to secure this grant. We have also benefited from its core services, since some of our preliminary studies involved measuring serum cytokines after vaccination,” said Penaloza-MacMaster.

He concluded: “The momentum within our local CFAR is exceptional, offering a diverse array of expertise that promotes collaboration and a multifaceted approach to addressing the HIV epidemic.”