The first human clinical trials testing a new strategy to protect against HIV infections have yielded promising early results, according to two separate reports published on Thursday in Science.
The trials tested "germline targeting" HIV vaccines, which aim to activate immune system B cells in their naive, or germline, state, inducing them to become specialized cells that produce broadly neutralizing antibodies (bnAbs).
By delivering a variety of HIV immunogens – typically, viral protein fragments - germline vaccines train the B cells to produce antibodies that can recognize and block a broad range of different strains of HIV from infecting healthy cells.
Germline targeting requires an initial dose to prime the correct B cells, and subsequent doses to guide their maturation until they can produce effective bnAbs, the researchers reported.
"Across the participants we saw an immune response that indicates that we're on the right track," Rogier Sanders of Amsterdam UMC, senior investigator on one of the trials, said in a statement.
"We saw that we can target the cells that we need to target with atomic precision. The next step is to further stimulate these cells to secrete broadly neutralizing antibodies," Sanders said.
In a separate paper, a different team of researchers reported on two early trials that used mRNA-encoded nanoparticles produced by Moderna to successfully prime the germline B cells, although a small proportion of patients had skin reactions to the vaccines.
The mRNA technology, similar to that used in Moderna's COVID-19 shots, would allow for faster vaccine development, the study authors said.
One of the trials was conducted in the United States and the other in Rwanda and South Africa. The majority of HIV patients live in Africa, but germline targeting has not previously been attempted there.
The researchers said the mRNA approach appeared to work with both North American and African populations, opening the door to further testing of germline-targeting vaccines for "African populations in most need of an HIV vaccine."
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