New HIV Vaccine Combines Adjuvants for Stronger, Longer Immune Response

A new study published in Science Translational Medicine reveals that researchers from MIT and the Scripps Research Institute have developed a potent single-dose HIV vaccine that triggers a strong and diverse immune response. The key lies in combining two powerful adjuvants- alum and a saponin-based nanoparticle- leading to long-lasting antigen exposure and significantly increased antibody production in mice.

Vaccines often include adjuvants, compounds that boost the immune system’s response to an antigen. Aluminum hydroxide, or alum, is commonly used in approved vaccines for hepatitis, while saponin-based adjuvants, like the SMNP nanoparticle developed by co-author Darrell Irvine, have shown enhanced efficacy in HIV vaccine trials. This study combined both alum and SMNP in a novel approach to understand how they jointly amplify the immune system’s response.

In their experiments, the researchers anchored dozens of HIV antigens (specifically MD39 proteins) onto alum particles, which were then paired with SMNP and injected into mice. They discovered that the dual-adjuvant formulation allowed the antigen to accumulate in the lymph nodes—where B cells mature and adapt—for up to 28 days, significantly longer than with single-adjuvant formulations. “As a result, the B cells that are cycling in the lymph nodes are constantly being exposed to the antigen over that time period, and they get the chance to refine their solution to the antigen,” said MIT’s J. Christopher Love.

Analysis of the B cells revealed a two- to threefold increase in antibody diversity in mice receiving the dual-adjuvant vaccine. This diversity is crucial in the fight against HIV, as broadly neutralizing antibodies are needed to protect against its many strains.

According to Love, "What's potentially powerful about this approach is that you can achieve long-term exposures based on a combination of adjuvants that are already reasonably well-understood, so it doesn't require a different technology. It's just combining features of these adjuvants to enable low-dose or potentially even single-dose treatments," The findings open the door to potent, single-dose vaccines not just for HIV but also for other infectious diseases like influenza and SARS-CoV-2.

Reference: Kristen A. Rodrigues, Yiming J. Zhang, Jonathan Lam, Aereas Aung, Duncan M. Morgan, Anna Romanov, Laura Maiorino, Parisa Yousefpour, Grace Gibson, Gabriel Ozorowski, Justin R. Gregory, Parastoo Amlashi, Richard Van, Maureen Buckley, Andrew B. Ward, William R. Schief, J. Christopher Love, Darrell J. Irvine. Vaccines combining slow release and follicle targeting of antigens increase germinal center B cell diversity and clonal expansion. Science Translational Medicine, 2025; 17 (803) DOI: 10.1126/scitranslmed.adw7499