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Moderna’s HIV Vaccine Trial Will Advance Many Companies’ mRNA Plans

In pursuit of a vaccine against HIV. (Photographer: Chris Hondros/Getty Images)

The first volunteers have rolled up their sleeves for a new kind of vaccine against HIV, developed by Moderna and the International AIDS Vaccine Initiative. Like Moderna’s Covid vaccine, the shot uses mRNA technology to deliver the instructions for key proteins needed to build an immune response.

The trial could be a pivotal moment for mRNA. With luck, it will demonstrate how the technology can be deployed in areas of medicine where progress has been slow or nonexistent. Researchers have spent decades working out a possible way to inoculate people against HIV, and mRNA will make it possible to test the theory much faster than expected.

This work should help companies including Pfizer, BioNTech and Sanofi, all accelerating their own efforts to design and test mRNA vaccines, to understand when the technology can — and can’t — make a difference in disease prevention. (Pfizer hopes to test an mRNA vaccine against shingles later this year.)

Creating an mRNA vaccine for HIV is trickier than making the kind of SARS-CoV-2 shots we’ve become familiar with. The mRNA Covid vaccines deliver the recipe for the spike protein, which the coronavirus uses to enter living cells. This causes immune cells to produce neutralizing antibodies against Covid, much as they would do if they had experienced a Covid infection.

With HIV, there’s no such simple recipe. HIV’s equivalent to the spike protein — its envelope glycoprotein — is wilier. It hides its vulnerable aspects, making it difficult for immune cells to generate antibodies against it.

An even bigger problem is that HIV starts to mutate within hours of infecting someone. Whereas Covid-19, in any individual infection, acts like a single virus, HIV behaves like “a swarm of slightly different viruses,” explains Warner Greene, director of the Gladstone Institutes’ Michael Hulton Center for HIV Cure Research, in San Francisco. People with HIV rarely develop neutralizing antibodies, and in the very few who do, the antibodies take years to evolve — far too long for them to effectively fight the virus. The immune system can’t keep up.

But what if the immune system could be given a head start? That’s the idea behind the Moderna/IAVI vaccine that began trials last week. The researchers will administer a series of shots to try to coax the immune system along that years-long process ahead of time so that when it is exposed to HIV, it can spring into action.

The Moderna/IAVI vaccine does this by targeting a small subset of B-cells that are capable of binding to HIV — albeit not very well. Gradually, with the right prodding from subsequent shots, those cells should develop the capability to pump out a collection of neutralizing antibodies capable of taking down an HIV swarm.

If this strategy sounds speculative, it is. But last year, results from a small clinical trial of a different immune nanoparticle coated in proteins showed that it might just work. This vaccine product, developed by Scripps Research immunologist William Schief, proved to be safe, and it homed in on the critical subset of B-cells and nudged them along the maturation process. 

What mRNA technology brings to this effort is the potential to collapse the time needed to develop and test the sequence of shots. Getting Schief’s recombinant protein vaccine from concept to clinical trial took three years, Mark Feinberg, president and chief executive officer of IAVI, told me. Creating the Moderna/IAVI vaccine using mRNA took just three months.

What could still take years is the iterative process of testing the first shot and learning from it to develop the second and maybe third shots needed to train the immune system to fight HIV.

Nevertheless, this is an experiment worth running. If this approach works, the world will finally get a much-needed HIV vaccine. And there could be side bonuses: Scientists would learn more sophisticated ways to train the immune system, eventually creating better vaccines for many other infections, such as malaria or the flu.

The HIV vaccine trial is also a good step forward in expanding the use of mRNA. Covid-19 has already demonstrated that the technology works. Soon we’ll find out what else it’s capable of.  

More from other writers at Bloomberg Opinion:

• Moderna Achieves a Tesla-Like Aura With Investors: Max Nisen and Liam Denning

• mRNA Vaccines Could Vanquish Covid Today, Cancer Tomorrow: Andreas Kluth

• Louis Pasteur’s Vaccine Successor Bets on mRNA: Max Nisen

This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.

Lisa Jarvis, the former executive editor of Chemical & Engineering News, writes about biotech, drug discovery and the pharmaceutical industry for Bloomberg Opinion.

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