Human Trials Illuminate Pathway for mRNA Vaccines Targeting HIV

Creating effective HIV vaccines may necessitate intricate formulations containing various viral proteins. Presently, two trials utilizing potential mRNA components have shown encouraging outcomes. The aim is to leverage mRNA technology for administering vaccines as a single dose rather than requiring multiple injections.

Typically, vaccines feature the virus’s outer protein, prompting the immune system to react against it. However, developing HIV vaccines poses significant challenges due to the virus’s proteins being heavily coated with sugars, which makes it tough for the immune system to generate antibodies. There’s also considerable variation across strains; therefore, even if an individual’s immune system can produce effective antibodies, these may only target a specific variant of the virus.

Nevertheless, a few individuals generate broadly neutralizing antibodies that are effective across multiple strains. Research in animals suggests that vaccines incorporating sequences of HIV proteins in various configurations can reliably elicit this broadly protective response, according to William Schief at the Scripps Institute in California.

The initial part of the vaccine comprises a modified viral protein aimed at stimulating the body to produce the essential B cells required for generating broadly neutralizing antibodies. The booster then encourages these cells to produce antibodies targeting external proteins.

This method highlights the advantages of mRNA vaccine technology, as mRNAs can be developed swiftly and conveniently, Schief states. “That’s a significant benefit.”

A single mRNA vaccine could encode multiple viral proteins simultaneously and has the potential to produce them in the body at different intervals, he adds. This implies that the mRNA HIV vaccine could potentially be administered as a single dose, even though several boosters typically follow. “Ideally, I’d prefer to administer one vaccine, with some components being released later,” Schief explained.

Earlier this year, his team shared promising results from preliminary human trials of the initial primers developed to stimulate B cells. Currently, his team is evaluating one of the subsequent boosters in another small study.

When volunteers received mRNA instructions for HIV external proteins integrated into the cell membrane, 80% generated antibodies shown to block infection in laboratory tests.

In this study, these antibodies were specific to one strain. Researchers anticipate that when boosters are administered sequentially, each component will be produced within the body in the correct order.

However, both trials reported a higher incidence of volunteers experiencing hive reactions, which have persisted for years. This reaction hasn’t been seen in any other mRNA vaccine trials or in non-mRNA vaccines incorporating HIV proteins, Schief notes. There appears to be an unknown factor related to delivering HIV proteins via mRNA that leads to this side effect. “It remains a scientific mystery at this time,” he states.

“The uncertainty surrounding the cause of this adverse effect makes it challenging to mitigate,” notes Hildegund Ertl, a vaccine expert associated with a company currently under exploration, Pharma5 in Morocco.

Ertl concurs that mRNA technology enables rapid testing of vaccine components but believes that the optimal final product could be delivered through different types of vaccines, such as those using empty viral shells. These alternatives can be stored at room temperature, unlike others that may require freezing, she points out.

Currently, there’s a medication called renacapavir, which offers nearly complete protection from HIV infection with two injections a year. Nevertheless, Schief believes a vaccine is still necessary. “We’re all striving to achieve this as quickly as possible,” he states, but even with the advancements in mRNA technology, an approved HIV vaccine may still be decades away.