Is the COVID-19 vaccine ready to move on from the original strain?

Scientists debate the benefits of bivalent and monovalent shots

By Nicole Karlis

Senior Writer

Published June 4, 2023 10:00AM (EDT)

Vaccines in an upward line graph (Getty Images/Andriy Onufriyenko)
Vaccines in an upward line graph (Getty Images/Andriy Onufriyenko)

This fall season could usher in another round of COVID-19 vaccines. But unlike before, it might be the first time people are injected with a dose that doesn't target the original strain of the novel coronavirus that led to worldwide shutdowns in 2020 in the first place.

True to its name, the current bivalent vaccine protects against both the original strain of the virus and omicron variants from BA.4 and BA.5 lineages. While people who were vaccinated early on in the pandemic received the monovalent Moderna and Pfizer-BioNTech COVID-19 vaccines, those are no longer authorized for use because data showed that the bivalent Moderna and Pfizer-BioNTech COVID-19 vaccines provided better protection against severe illness and hospitalization as the virus mutated.

While the U.S. Food and Drug Administration (FDA) is still working on a plan for what the next generation of COVID-19 vaccines will look like, and when they will be available, a World Health Organization's (WHO) advisory group recently released recommendations suggested that the vaccine should next only target descendants of the predominant XBB.1 strain. In other words, targeting the original strain is no longer a priority.

The recommendation is sparking debate on whether or not bivalent shots were effective in the first place — and if the world is ready to move on from boosting immunity against the original strain.

"The bivalent booster did not seem to be very effective for preventing severe disease among those who are 18-64 years old in this large Finnish study, although there was protection for those who are older than 65 against hospitalization for approximately 3 months," Dr. Monica Gandhi, an infectious disease doctor and professor of medicine at the University of California–San Francisco, told Salon via email. "I agree with the WHO that new booster shots should target XBB subvariants as these will be the most prevalent subvariants in the next booster campaign."

"The bivalent booster did not seem to be very effective for preventing severe disease among those who are 18-64 years old."

The changing landscape of the COVID-19 vaccines has been in motion for some time now. Earlier this year, an FDA advisory panel agreed that moving forward, COVID-19 vaccines should be given on a yearly basis and target whatever variant is seen as the biggest threat, similar to how the influenza vaccine works. Soon, on June 15, FDA advisers will discuss which strains should be part of the vaccine so companies can move forward with production.

To date, the COVID-19 vaccines have only undergone one modification when the bivalent version was introduced in September 2022. According to the CDC, only 17 percent of the U.S. received the booster. There has been some chatter that while well-intended, keeping the original strain in the bivalent booster did more harm than good. Indeed, one study found no significant difference between the two vaccines and neutralizing COVID-19.

L.J. Tan, chief policy and partnerships officer at Immunize.org, told Salon he thinks it's difficult to make a definitive statement that the bivalent boosters weren't as effective as the monovalent ones.

"It's very hard to tease that apart because the bivalent was launched when immunity was already pretty high," Tan said. "It's cherry picking data, you can say, 'Oh, we did the bivalent and it doesn't prevent as many infections as it used to,' but it's hard to tease out what the impact of obviously pre-existing immunity has to do with someone that, and I think it's tricky to say that monovalent versus bivalent, that one's better than the other."


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As pediatrician Paul Offit explained in an op-ed in the New England Journal of Medicine, what could be cast aside as a failure could have actually been a result of "imprinting."

"The immune systems of people immunized with the bivalent vaccine, all of whom had previously been vaccinated, were primed to respond to the ancestral strain of SARS-CoV-2," Offit wrote. "They therefore probably responded to epitopes shared by BA.4 and BA.5 and the ancestral strain, rather than to new epitopes on BA.4 and BA.5."

Currently, the latest omicron variant XBB is fueling a resurgence in COVID-19 cases in China. Is this more evidence that the FDA should move forward with approving XBB-only vaccines?

"I also think turning towards whole virus vaccines (like Covaxin in India) can circumvent some of the immune evasiveness we are seeing in our current boosters that only contain the spike protein, since the spike protein changes so frequently in the new variants or subvariants," Gandhi said.

""I think omicron represents the endpoint of the evolution of the virus for its fitness."

Tan said he agrees that a monovalent is best, in part because it's easier to produce and will be more accessible in countries of lower socioeconomic status. However, he did say there is a little bit of data to suggest that vaccinating against both the original strain and omicron "creates a little bit more cross reactivity against potentially new strains that arise."

"I can see both sides and hence you see me jumping back and forth a little bit, but the truth of the matter is, I think the viral inflammation is slowing down and I think we're going to be seeing mostly omicron subvariants," he said. "If we're going to think about the fact that it's global environment and what happens in China is going to come out, and it's already out and it's happening elsewhere, it makes sense that our boosters should be focused on XBB variants."

Indeed, while there have previously been fears that the virus could keep mutating into something worse — that could possibly evade the immunity built up around the world — Tan said he doesn't expect that to happen.

"I think omicron represents the endpoint of the evolution of the virus for its fitness," he said, referring to the virus's ability to transmit and evolve. "I think if it mutates further it's going to lose its fitness."


By Nicole Karlis

Nicole Karlis is a senior writer at Salon, specializing in health and science. Tweet her @nicolekarlis.

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