Better HIV vaccination with increasing small doses

Better HIV vaccination with increasing small doses
Better HIV vaccination with increasing small doses

Repeatedly administering a small amount of a vaccine, in an increasing dose, seems to be a good vaccination strategy for HIV. That is what a study with monkeys shows in the scientific journal on Wednesday Nature popped up. As a result, antibody-producing immune cells, B cells, can develop and refine their antibodies in lymph nodes for months instead of weeks. The finding is an important step towards better vaccines against difficult pathogens such as HIV and malaria, which are resistant to any vaccination to date.

No virus is as variable as the human immunoefficiency virus (HIV), which causes the disease AIDS. HIV hides in the body and changes as it infects cells. As a result, 40 years after the virus was discovered, there is still no effective vaccine. Virologists are frantically searching for a good vaccine strategy.

animals

For this study, two groups of four rhesus monkeys were vaccinated every other day for 12 days. The series consisted of seven injections, each with a slightly higher dose of an HIV protein, totaling 100 micrograms. The vaccine contained the envelope protein on the outside of the virus that allows it to enter cells. One group received a booster shot after ten weeks, the other only after seven months. A third group, the control group, received a single dose of 100 micrograms, and a booster shot after ten weeks.

The researchers looked in the monkeys’ lymph nodes for specialized areas where immune cells are ‘trained’. Certain immune cells, B cells, recognize a pathogen or part thereof in a vaccine, and then go to so-called germinal centers in lymph nodes. There, those cells mature and evolve. They improve and refine the antibodies they make, so that they recognize the pathogen even better.

In the animals that had received the trial vaccine in the incremental doses, those B cells continued to develop for at least six months, without a booster vaccination, and much longer than expected. After ten weeks, the monkeys that received the new vaccine regimen had 186 times more B cells than monkeys immunized in the conventional way with two shots. Those B cells not only made much more antibodies, but also of much better quality. Better even than in the monkeys that did receive a booster after the seven injections after ten weeks. They did have a new peak in the number of antibodies after that booster, but they were not of the same high quality.

An interesting study, says virologist Rogier Sanders. He develops and tests HIV vaccines at the Amsterdam UMC and, among other things, made the envelope protein used for the study. “It is striking that the specialization of B cells is still ongoing after six months. Until now, everyone thought that it would be over after a few weeks.”

He points out that in the control group, which received the standard vaccination, another, less effective adjuvant was used in the vaccine, the so-called adjuvant. “The vaccines that the test group received contained a much better adjuvant. So it cannot be ruled out that the better immune response in that group is due to this.” The findings need to be further explored with newer vaccines that can train B cells even better.

Coronavirus variants

Seven shots in twelve days is very impractical for many people, especially in southern Africa where HIV is common. Work is underway on vaccine capsules that release small amounts of vaccine into the muscle for weeks, says Sanders. There are even capsules that can always deliver a different vaccine, like a magic ball. “In any case, we now know that we will never make it against HIV with one vaccine. You need vaccines against different parts of the virus, which you administer sequentially. HIV is extremely diverse, compared to which the coronavirus variants that arise are child’s play.”

The article is in Dutch

Tags: HIV vaccination increasing small doses

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