Ragon Institute 
A multi-institutional study published in Science Immunology, led by the Batista Lab at the Ragon Institute, in collaboration with researchers at University of Pennsylvania, Scripps Research Institute, Columbia University, MIT, and others, demonstrates that a single immunization can rapidly generate antibodies capable of neutralizing a broad range of HIV strains, thereby offering a potential path toward simpler HIV vaccine regimens.
Developing an effective HIV vaccine has proven exceptionally difficult, largely because the virus is so diverse. While some people living with HIV naturally develop “broadly neutralizing antibodies” that can block many viral strains, current vaccine strategies to elicit these antibodies typically require complex, multi-dose regimens administered over months or years.
The team took a different approach. They created a mouse model whose B cells carry the precursor of a broadly neutralizing antibody originally identified in rhesus macaques infected with a simian-human hybrid virus. This “macaquized” mouse model allowed them to test whether a carefully designed immunogen could guide these precursor B cells to mature into antibody-producing cells capable of broad neutralization.
The results were notable. A single immunization with an immunogen was enough to drive the B cells through a maturation process closely mirroring what happens in macaques, but in a much shorter timeframe. The resulting antibodies could neutralize a diverse panel of HIV strains.
When the team followed the initial shot with a boost using either the same immunogen or a modified version, breadth and potency improved further. Structural analysis revealed how these antibodies recognize and neutralize such a wide variety of viral strains.
The findings suggest that combining insights from non-human primate infection studies with precision-designed immunogens could enable simpler, more streamlined HIV vaccination approaches, potentially reducing the number of doses needed to achieve protective immunity.