Experimental COVID-19 vaccine may outsmart future coronavirus variants

The new COVID-19 booster shots going up in arms across the country are being prized for their ability to recognize the distinctive spike protein shared by BA.4 and BA.5, the omicron strains that are currently almost 90% of the coronavirus samples currently in circulation are in the United States

But sooner or later, mutations in the spike protein will allow the virus to slip past the antibodies trained to recognize its predecessors. The booster vaccines can still protect people from getting seriously ill, but they become less effective at preventing infection.

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

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

The new shot needs to be tested on larger animals before trying it on humans, and there’s no guarantee the results will be the same. But scientists said the approach could result in a unified vaccine that offers more durable protection against a virus that has been shown to have spawned new variants.

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

Other scientists 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 one step ahead of the coronavirus.

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

The current crop of COVID-19 vaccines has saved an estimated 19.8 million lives worldwide. However, as the virus has evolved, its effectiveness in preventing infection has diminished, leading to more illness, more time away from work and school, and more people at risk of long COVID.

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

The spike protein of the SARS-CoV-2 virus is in a way the double-edged sword of the pandemic. It’s the primary target of all four COVID-19 vaccines currently available in the US, but it’s also the part of the virus most likely to take advantage of random mutations that allow it to bypass the immunity those vaccines offer must.

There’s a reason the spike protein, or S in virology’s shorthand, is so vulnerable to evolutionary pressures: it’s the part of the virus that initiates infection by entering a host cell. If the spike cannot do its job, the virus cannot survive.

The second target of the experimental vaccine is the nucleocapsid protein, or N. It’s at the core of the virus and has little reason to change. But once inside a host cell, it plays an essential role in allowing the coronavirus to make copies of itself.

Hu and his colleagues used the same mRNA technology used in the Pfizer-BioNTech and Moderna vaccines to encode instructions for making harmless copies of both the S and N proteins. Once these copies are made, the immune system recognizes them as a threat and learns to respond accordingly.

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

Exposure of cells to N did not elicit the production of neutralizing antibodies. The study authors expected this, since N is not involved in helping the virus find its way into a host cell. However, the exposure elicited a strong T-cell response that helps clear the virus from the cell.

Next, the researchers injected the animals with a bivalent vaccine that simultaneously targeted S and N. The immune response was significantly stronger: none of the eight mice tested had viral RNA in their lungs. In contrast, seven out of eight mice immunized with a shot that only targeted S had detectable levels of viral RNA.

Additional tests were conducted on hamsters exposed to the Delta variant. The results were similar: viral load was undetectable in animals receiving the combination vaccine and their pulmonary pathology was clear. They also had less virus in their upper respiratory tract compared to hamsters that received the S-only vaccine, which could make them less likely to transmit the virus to others.

Hamsters exposed to the Omicron variant also performed better with the bivalent vaccine. Four out of five hamsters that got it had no detectable virus, compared to just one out of five hamsters vaccinated with a vaccine that only targeted S. The animals that received the bivalent vaccine had no lung damage, while those that received the S vaccine alone developed lesions on their lungs. The bivalent vaccine also reduced viral loads in the upper respiratory tract.

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

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

The S protein “gives you good antibodies, and N gives you amazing T cells,” he said. “It’s the interaction between the antibodies and the T cells – if you have both, you get the best of both worlds.”

One thing not addressed in the new study is how long the benefits of the combination vaccine would 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 estimate the longevity of the vaccine.

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

https://www.latimes.com/science/story/2022-09-14/experimental-covid-19-vaccine-may-outsmart-future-coronavirus-variants Experimental COVID-19 vaccine may outsmart future coronavirus variants

Russell Falcon

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