A new study co-led by the Batista Lab at the Ragon Institute and Scripps/IAVI shows that a single mRNA-based vaccine mix can jump-start the early steps toward several promising HIV-fighting antibodies at the same time. Because HIV is extremely diverse, a successful vaccine would likely need to train the immune system along multiple routes, not just one.

The team tested “germline-targeting” mRNA vaccine ingredients which are molecules designed to wake up the rare B cells that can later mature into broadly neutralizing antibodies. In mouse models built to mimic how rare these cells are in people, the mRNA mix activated starting cells for four well-studied HIV antibody targets on the virus’s Envelope protein.

When given as a cocktail, the mRNA approach produced more balanced responses across targets than comparable protein cocktails. The ability to display vaccine antigens on cell membranes via mRNA may help more of these rare B cells cross the activation threshold and enter germinal centers where they begin the long process of improving their antibodies.

As a first “prime,” the shot didn’t yet create broadly neutralizing activity in blood and boost doses are still needed to guide these early responses to maturity. However, the results suggest that combining mRNA-encoded ingredients could reduce clinic visits and make multi-target HIV vaccines more practical over time. An important consideration is that mRNA mixtures are easier to formulate (no adjuvant picking) and can be updated by adding new components in the future.

This work offers a blueprint for multi-epitope HIV vaccination by using mRNA to launch several protective antibody pathways at once, then building them up with targeted boosts.