Researchers at Karolinska Institutet, in collaboration with colleagues at The Scripps Research Institute and Emory University, have developed a new vaccine strategy that has generated antibodies capable of neutralising highly divergent HIV variants. The study, published in the journal Nature, provides new insights into how the immune system can be guided towards a particularly protected part of the virus.
HIV mutates rapidly, making it difficult to develop an effective vaccine. One major challenge has been to stimulate the immune system to produce so‑called broadly neutralising antibodies that recognise parts of the virus shared by many HIV variants.
In the study, the researchers focused on a small structure located at the very top of the virus’s surface protein, known as the apex, which is important for the protein’s three-dimensional structure. The apex is similar across many HIV variants but is shielded by dense layers of sugar molecules, making such binding difficult to achieve.
The researchers developed a strategy in which specially designed HIV proteins were attached to tiny fat particles, known as liposomes. This enabled multiple copies of the virus’s surface protein to be presented to the immune system simultaneously, thereby strengthening the immune response.
The vaccine strategy was tested in an animal model in which macaques were immunised with liposomes linked to a selected HIV protein and then given booster doses in which the protein was gradually altered. The aim was to train the immune system to recognise features that are shared across different HIV variants.
Resembles antibodies that develop in humans
With this strategy, all vaccinated animals developed antibodies that neutralised a wide range of HIV variants. When the researchers analysed the antibodies in more detail, they found that they bind to the virus’s apex in a way similar to antibodies that sometimes develop in humans after long‑term HIV infection.
“The study shows that it is possible, through vaccination, to steer the immune system towards this specific part of the HIV surface protein,” says Gunilla Karlsson Hedestam, professor at the Department of Microbiology, Tumour and Cell Biology at Karolinska Institutet and a shared senior author of the study.
“This is an important step towards understanding how an HIV vaccine could be designed. Discussions are now underway about how the strategy could be taken forward into clinical studies,” she continues.
The study was funded by the US National Institutes of Health (NIH). The researchers report no conflicts of interest.
Publication: ”Vaccine generates broadly cross-neautralizing antibodies to the HIV Env apex, Javier Guenaga, Monika Adori, Shridhar Bale, Swastik Phulera, Ioannis Zygouras, Fabian-Alexander Schleich, Xaquin Castro Dopico, Sashank Agrawal, Miyo Ota, Richard Wilson, Jocelyn Cluff, Tamar Dzvelaia, Marco Mandolesi, Wen-Hsin Lee, Agnes A. Walsh, Mariane B. Melo, Laurent Verkoczy, Darrell J. Irvine, Martin Corcoran, Ian A. Wilson, Diane Carnathan, Guido Silvestri, Andrew B. Ward, Gabriel Ozorowski, Gunilla B. Karlsson Hedestam, Richard T. Wyatt, Nature, online 29 april, doi: 10.1038/s41586-026-10429-3
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