Drawing out the delivery of an HIV vaccine candidate over a number of days yields a much stronger immune response than providing it to monkeys in a single shot.
Publishing their findings in Cell, researchers compared three delivery methods of a vaccine candidate among rhesus macaque monkeys. In one method, the vaccine was given in a single shot. In the second, the monkeys received an implant that provided the vaccine over time through what is known as an osmotic pump strategy. And in the third, the monkeys received escalating doses of the vaccine every other day for 12 days.
The researchers used a new method to monitor the development of HIV antibodies in the lymph nodes of the monkeys. This process allowed them to draw small samples of what are known as germinal center cells. Germinal centers, located in the lymph nodes, are where B cells manufacture antibodies. When it comes to responding to HIV, such B cells are selected for survival by T follicular helper (TFH) cells such that the B cells with the most promise in fighting the virus will progress through the body’s immune system pipeline. During this process, the immune system further refines the B cells in an effort to yield the most effective antibodies to the virus.
The researchers found that the single-shot method of delivering the vaccine gave rise to a poor immune response in the monkeys. By stark contrast, the two slow-delivery mechanisms were associated with a much greater number of antibodies, which were also more effective. Animals in the latter two study groups developed HIV-specific B cells that were activated for longer; this afforded them more time to work with TFH cells to refine both the strength of antibodies and their ability to bind onto the virus. Over time, these B cells began to produce antibodies capable of neutralizing the virus and binding to key points on its surface.
The investigators next hope to find practical ways to deliver vaccines to humans in a similarly drawn-out manner and are considering, for example, using degradable capsules.
To read a press release about the study, click here.
To read the study abstract, click here.