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In-Depth: How San Diego scientists designed the first mRNA vaccine for HIV

HIV spike protein
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SAN DIEGO (KGTV) – Researchers have just launched the first human trial of an HIV vaccine using mRNA technology, and it was designed by scientists in San Diego.

Dr. William Schief and his team at Scripps Research have been working on this concept for an HIV vaccine for more than a decade. He says borrowing some technology from Moderna’s COVID vaccine gives them something they haven’t had before: speed.

“It will allow us to do clinical trials more quickly. If we get a positive result, we can act on that positive result and do the next clinical trial with the next design much more quickly. We don’t have to wait five years,” he said.

At its core, the goal of this experimental HIV vaccine is the same as the vaccines for COVID: block the spikes on the virus so it can’t infect cells.

The problem is that HIV’s spikes are constantly mutating.

Some scientists estimate there are as many variants of HIV within one person as there are variants of the flu worldwide.

“There are literally millions of HIV variants in the world right now, and we need to induce antibodies that can bind to all those different spikes,” Dr. Schief said. “Not just the 10 [COVID-19] variants you’d like to protect against.”

There have been seven full-scale human trials on other HIV vaccines; all have failed. But Dr. Schief’s team is trying a new approach.

“Our strategy to make a vaccine is a sequence of different shots, of different immunogens, to teach the immune system to make the right kinds of antibodies that could neutralize millions of different variants,” he said.

Dr. Schief compares the concept to training an Olympic athlete from birth. They start by identifying the rare babies with promising genetic traits, then slowly build their muscles one shot at a time.

In this case, they search for the 1 in 1 million infant B cells with the right traits. Once trained, B cells make antibodies.

This week, Dr. Schief’s team announced results from an initial human trial showing they could successfully find these rare B cells and start the process of training them, a milestone after a decade of work.

“That was totally gratifying,” he said.

Now, they’ve launched a second human trial, borrowing mRNA technology from Moderna. They’ll vaccinate 56 healthy, HIV-negative volunteers with two shots of this vaccine. It’s essentially the same Scripps design but in mRNA code.

Their goal isn’t to block HIV yet. It’s to get those naive B cells a little closer to Olympic athletes. Dr. Schief estimates it will take four or five shots to fully train these cells to make so-called “broadly neutralizing antibodies.” These are antibodies capable of binding to a large swath of HIV variants.

Since mRNA vaccines are easy to reprogram, scientists can rapidly tweak the recipe to find the ultimate way to train these cells.

The clinical trial using these mRNA shots is being conducted at George Washington University and the Fred Hutchinson Cancer Research Center in Seattle.