For a vaccine to work, it must produce antibodies in immunized people – antibodies that are ready to neutralize subsequent intruders. For a vaccine to be safe, it must do so for the vast majority without major side effects or reactions.
A new HIV vaccine candidate faces the usual challenges of early-stage clinical trials, succeeding in one aspect but encountering some obstacles in the other.
This is progress nonetheless, as its developers have reformulated the vaccine to improve its safety in future studies – while their latest results show how the vaccine successfully generates broadly neutralizing antibodies in a small number of people.
Broadly neutralizing antibodies (bnAbs) targeting HIV were discovered in the early 1990s, at the height of the HIV/AIDS epidemic, in some HIV-positive people.
Their potential was immediately obvious: bnAbs can recognize and neutralize multiple strains of HIV, a genetically diverse and shape-shifting virus that shuffles its outer envelope to evade immune detection.
But despite nearly four decades of research, a vaccine capable of generating bnAbs in humans – let alone any HIV vaccine – remains woefully elusive.
Natural infections give us an idea of how difficult it is to get the immune system to produce these powerful antibodies: bnAbs only materialize in about 10% to 25% of people living with HIV, and they can take years to develop.
So the news that a vaccine candidate tested in a small clinical trial generated bnAbs in several people after two doses is promising.
“It was very exciting to see that with this vaccine molecule, we could actually elicit neutralizing antibodies within a few weeks,” said Wilton Williams, an immunologist at the Duke Human Vaccine Institute (DHVI) who led the study.
The vaccine candidate targets HIV-1, the more common of the two types of HIV, and more specifically a part of its outer envelope which remains stable even when the virus mutates.
The phase I clinical trial, which began in 2019, enrolled 24 healthy participants, 4 of whom received a placebo. But the trial was halted after one person had a severe allergic reaction (after their third dose) to one of the vaccine’s components, polyethylene glycol (PEG), used to stabilize the formulation.
Before the trial was stopped, 5 people received three of the four planned doses, and another 15 people received only two.
The vaccine has since been reformulated without PEG so the trial can resume testing a PEG-free version. In the meantime, Williams and his colleagues analyzed the available data and found that the vaccine caused a strong immune response after two doses.
The long-sought elite neutralizers, bnAbs, were also generated in two of the five people who received three injections before the trial was stopped. The most potent of these antibodies neutralized 15 to 35 percent of HIV strains in cellular experiments.
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“This work is a major breakthrough because it shows the feasibility of inducing antibodies with immunizations that neutralize the most difficult strains of HIV,” says Barton Haynes, an immunologist at DHVI.
“Our next steps are to induce more potent neutralizing antibodies against other HIV sites to prevent escape of the virus. We’re not there yet, but the path forward is now much clearer.”
It’s certainly good to have options, even if it’s only in the early stages of development. Other promising strategies to develop effective vaccines against different strains of HIV have failed in late-stage clinical trials, serving as a “stark reminder” of the challenges of developing an HIV vaccine.
However, other treatments succeed while potential vaccines fail. In December 2023, a landmark trial showed that preventative treatment reduced the chances of contracting HIV by 86% if used consistently.
The DHVI research was published in Cell.
News Source : www.sciencealert.com
Gn Health
