New vaccine strategy triggers antibodies capable of blocking diverse HIV variants

An international research team, co-led by SciLifeLab researcher Gunilla Karlsson Hedestam (Karolinska Institutet), presents a new vaccination strategy that induces broadly neutralizing antibodies against HIV. The study is published in Nature.

Developing an HIV vaccine has been extremely challenging due to the virus’ genetic diversity and rapid mutation of its envelope glycoprotein (Env). However, some structures on the Env trimer are functionally constrained and conserved across variants, making them relevant vaccine targets.

In the study, the investigators used structurally designed Env trimers from different virus variants, displayed on liposomes. When these were administrated sequentially, they stimulated antibodies that could block infection with a wide range of HIV clinical isolates.

By isolating monoclonal antibodies and characterizing them by high-resolution cryo-electron microscopy, the authors identified antibodies that bind the apex of the Env trimer. The results show that it is possible to guide the immune system to respond to the conserved structures on Env. 

“For the first time since HIV vaccine candidates began to be evaluated in the 1990s, we see robust vaccine-elicited responses, and we could confirm the specificity of the response by isolating monoclonal antibodies that bind the Env apex and block infection by clinical HIV isolates,” says Gunilla Karlsson Hedestam.

In the study the research team used the IgDiscover pipeline, originally developed with support from SciLifeLab, to analyze immunoglobulin gene repertoires and characterize the antibody response.

The study was led by Gunilla B. Karlsson Hedestam (KI) and Richard Wyatt (Scripps Research Institute), with Monika Ádori (SciLifeLab/KI) as co-first author.

DOI: 10.1038/s41586-026-10429-3

Contributing authors to the study, from left: Fabian Schleich, Gunilla Karlsson Hedestam, Ioannis Zygouras, Monika Ádori and Martin Corcoran.