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Experimental COVID-19 vaccine could outsmart future coronavirus variants

A nurse prepares a syringe of COVID-19 vaccine. An experimental vaccine aims to get ahead of new variants by preparing the immune system to recognize a stable part of the coronavirus. (Brian van der Brug/Los Angeles Times)

New COVID-19 booster shots entering weapons across the country are valued for their ability to recognize the distinctive spike protein shared by BA.4 and BA.5, the Omicron strains that currently account for nearly 90% of specimens of coronaviruses currently circulating in the United States

But sooner or later, mutations in the spike protein will allow the virus to override formed antibodies to recognize its predecessors. Reminders can still prevent people from getting seriously ill, but they will become less effective at preventing infections in the first place.

An experimental vaccine aims to solve this problem by preparing the immune system to recognize both the spike protein and a much more stable second viral protein.

When tested in small animals, this bivalent vaccine provided stronger protection than alternatives that targeted only one of the proteins. And, although the vaccine design was based on an early strain of coronavirus from Wuhan, China, it remained effective against Delta and Omicron variants.

The new vaccine will need to be tested in larger animals before it is tried in humans, and there is no guarantee that the results will be the same. Still, the scientists said the approach could lead to a single vaccine that offers longer-lasting protection against a virus with a proven record of creating new variants.

“We see it as a one-stop solution for all variants of COVID,” said Haitao Hu, an immunologist at the University of Texas Medical Branch and lead author of a study describing the vaccine in Wednesday’s edition of the journal Science Translational Medicine.

Other scientists who were not involved in the study agreed that if the vaccine works as well in humans as it does in mice and hamsters, it could help us stay ahead of the coronavirus.

“It’s a great idea,” said Dr. Paul Offit, a virologist and immunologist at the University of Pennsylvania who was not involved in the study. “You could have argued that we should have done that at the start.”

Current COVID-19 vaccines have saved an estimated 19.8 million lives worldwide. Yet as the virus has evolved, its effectiveness in preventing infection has diminished, which means more illness, more time spent away from work and school, and more people at risk of developing a long COVID.

The situation forced scientists to catch up with the variants, Hu said: “You’re still one step behind.”

The spike protein of the SARS-CoV-2 virus is in some ways the pandemic’s double-edged sword. It’s the key target of the four COVID-19 vaccines currently available in the United States, but it’s also the part of the virus most likely to take advantage of random mutations that allow it to dodge the immunity those vaccines are supposed to. provide.

There’s a reason the spike protein, or “S” for virology for short, is so sensitive to evolutionary pressure: it’s the part of the virus that initiates an infection upon entering a host cell. If the woodpecker can’t do its job, the virus can’t survive.

The second target of the experimental vaccine is the nucleocapsid protein, known as “N”. It is located in the core of the virus and has little reason to change. But once inside a host cell, it plays a vital role in allowing the coronavirus to make copies of itself.

Hu and his colleagues used the same mRNA technology as the Pfizer-BioNTech and Moderna vaccines to encode the instructions to make harmless copies of the S and N proteins. Once these copies are made, the immune system recognizes them as threats and learns to react accordingly.

The researchers began their tests by injecting small groups of mice with vaccines targeting only the N protein. The animals mounted an immune response, but only a modest one, Hu said.

Exposure of cells to N did not trigger the production of neutralizing antibodies. The study authors expected this, because N is not involved in helping the virus enter a host cell. The exposure, however, induced a strong T-cell response, which helps clear the virus from the cell.

Next, the researchers injected the animals with a bivalent vaccine that targeted S and N at the same time. The immune response was much stronger: no viral RNA was detected in the lungs of the eight mice that received the bivalent vaccine. In contrast, among eight mice immunized with a vaccine targeting only S, seven had detectable amounts of viral RNA.

Additional tests were performed on hamsters exposed to the Delta variant. The results were similar: the viral load was undetectable in the animals that received the combination vaccine and their lung pathology was clear. Compared to hamsters that received the S vaccine only, they also had less virus in their upper respiratory tract, which may make them less likely to transmit the virus to others.

Hamsters exposed to the Omicron variant also fared better with the bivalent vaccine. Four of five hamsters that received it had no detectable virus, compared to only one of five hamsters that were vaccinated with a vaccine targeting only S. Animals that received the bivalent vaccine had no lung lesions, while that those who received the S vaccine only the vaccine developed lesions on their lungs. The bivalent vaccine also reduced viral loads in the upper respiratory tract of hamsters.

The Texas team isn’t the first to tackle spike and core proteins simultaneously. Culver City’s ImmunityBio has developed a COVID-19 vaccine with a similar structure that is currently undergoing clinical trials in South Africa.

The new study “confirmed that when you have S plus N, you can experience multivariate protection,” said Dr. Patrick Soon-Shiong, executive chairman of ImmunityBio. (Soon-Shiong also owns the Los Angeles Times.)

Protein S “gives you great antibodies, and N gives you amazing T cells,” he said. “It’s the interaction between antibodies and T cells – by having both, you get the best of both worlds.”

One thing the new study didn’t address is how long the benefits of the combination vaccine last, said Stanley Perlman, a microbiologist and immunologist at the University of Iowa. The animals were tested two weeks after receiving their last dose, and the study authors acknowledged that longer experiments were needed to assess the longevity of the vaccine.

Hu said his team’s next step is to study the vaccine in non-human primates. If all funding and approvals are secured, it could be completed within six months, and if the results are good, human trials would be next, he said.

This story originally appeared in the Los Angeles Times.

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