Experimental COVID-19 vaccine could outperform future variants

The new booster shots of COVID-19 spreading across the country are valued for their ability to identify the distinct spike protein shared between BA.4 and BA.5, the Omicron strains that currently account for nearly 90% of coronavirus samples now circulating in the states. United

But sooner or later, mutations in the spike protein will allow the virus to pass through antibodies that have been trained to recognize its ancestors. Boosters may protect people from developing serious illness, but they will become less effective at preventing infection 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 second – much more stable – viral protein.

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

The new shot must be tested on larger animals before trying it on humans, and there is no guarantee that the results will be the same. However, the scientists said this approach could lead to a one-size-fits-all vaccine that provides lasting protection against the virus with a proven track record of producing new types of vaccine.

“We think it’s a one-time solution to all COVID variants,” said Haitao Hu, an immunologist at the University of Texas Branch of Medicine and senior author of a study describing the vaccine in Wednesday’s edition of 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 University of Pennsylvania virologist and immunologist, who was not involved in the study. “You could argue that we should have done that in the beginning.”

Current COVID-19 vaccines have saved an estimated 19.8 million lives worldwide. However, as the virus has evolved, its effectiveness in preventing infection has waned, which means more illness, more time away from work and school, and more people at risk of contracting COVID for an extended period.

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

The thorny protein on SARS-CoV-2 is in some ways the double-edged sword of the epidemic. It’s the main target of all four COVID-19 vaccines currently available in the United States, but it’s also the part of the virus that is most likely to benefit from the random mutations that allow it to evade the immunity that those vaccines are intended to provide.

There’s a reason the spiny protein, or “S” for virology for virology, is vulnerable to evolutionary pressure: It’s the part of the virus that initiates infection by entering a host cell. If the virus can’t do its job, the virus can’t survive.

The second target of the experimental vaccine is a nucleocapsid protein known as “N.” It is at the core of the virus and has no reason to change it. But once it enters the host cell, it plays an essential role in allowing the coronavirus to make copies of itself.

Hu and colleagues used the same mRNA technology as the Pfizer-BioNTech and Moderna vaccine to encode instructions to make harmless copies of both the S and N proteins. Once those copies are made, the immune system recognizes them as threats 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 did mount an immune response, Hu said, but it was a modest response.

Exposing cells to nitrogen does not stimulate production of neutralizing antibodies. The study authors expected this, because N is not involved in helping the virus make its way into the host cell. However, exposure triggered a robust T-cell response, which helps clear the virus from the cell.

Next, the researchers injected the animals with a bivalent vaccine targeting 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. By contrast, among eight mice immunized with an injection that targeted only S, seven had detectable amounts of viral RNA.

Additional tests were performed on hamsters exposed to the delta variable. The results were similar: the viral load was undetectable in the animals that received the combination vaccine, and lung disease was evident. Compared to hamsters that only got the S vaccine, they also had fewer upper respiratory tract viruses, which could make them less likely to spread the virus to others.

Hamsters exposed to the Omicron variant fare better with the bivalent vaccine as well. Four out of five hamsters who received the vaccine had no detectable virus, compared to only one of five rats vaccinated with an injection targeting S. 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 go after spike proteins and nucleocapsids at the same time. ImmunityBio of Culver City 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 have multivariate protection,” said Dr. Patrick Soon-Shiong, CEO of ImmunityBio. (Soon Xiong also owns the Los Angeles Times.)

S protein “gives you good antibodies, while 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 of the things the new study didn’t address is how long the benefits of the combination vaccine will last, said Stanley Perlman, a microbiologist and immunologist at the University of Iowa. The animals were tested two weeks after receiving their final dose, and the study authors acknowledge the need for longer trials to measure the longevity of the vaccine.

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

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