New research from a team of San Francisco scientists raises questions about the usefulness of a new Omicron-specific COVID vaccine for next fall, as the virus is evolving rapidly and the risk of the disease is likely to rise.
The study, published in the journal Nature, provides mounting evidence that federal policymakers must make a difficult decision: Should today’s vaccine be changed—and if so, how?
Time is of the essence, so a decision is planned for next month. It comes as the nation finds itself in the midst of a new wave of infections linked to new Omicron variant subtypes, averaging more than 105,000 new cases per day for the first time since February. An estimated 58% of all new US cases are linked to the BA.2.12.1 hypertransmissible omicron variant, which is spreading rapidly among both vaccinated and previously infected individuals.
“We should try to develop vaccines that offer broad protection against many variants,” said Dr. Charles Chiu, an infectious disease specialist and microbiologist at UC San Francisco who contributed to the study.
“I’m skeptical that an Omicron vaccine will be that useful against the new variants that are coming in the future,” he said. “We shouldn’t be playing ‘Whac-A-Mole.’ “
The UCSF team found that unvaccinated individuals infected with the original COVID omicron variant called BA.1 were not protected from infection by other strains of the COVID virus.
“In the unvaccinated population, an infection with Omicron could roughly correspond to a vaccination,” said virologist Dr. Melanie Ott, director of the Gladstone Institute of Virology and co-author of the new study. “It offers a little protection against COVID-19, but it’s not very comprehensive.”
This suggests that an Omicron-based vaccine would also provide lousy protection against future strains of the virus — either new generations of Omicron or whatever other variants will prevail.
“Omicron immunity really doesn’t hold up against the new variants,” she said.
Vaccine manufacturer Pfizer is testing the efficacy of a booster and primary vaccine specifically targeting Omicron’s BA.1. It also tests bivalent and multivalent vaccines, meaning they target different strains of the virus.
Moderna is testing two versions of its mRNA vaccine. One is specifically directed against the omicron BA.1 variant, the other is bivalent.
The decision on the vaccine formulation will be made by Food and Drug Administration regulators after their June 28 meeting.
Why not previous infection with omicron help ward off future infections? There are two possible reasons, Ott said.
Omicron causes milder disease, and that could lead to milder immunity, she said.
Second, the new subtypes of omicron are genetically distinct, she said. They have mutations that change a key amino acid called L452, which may help them evade immunity.
This is of concern as an estimated 40% to 50% of Americans were infected with the original omicron BA.1 variant.
Without additional vaccination protection, they are susceptible to reinfection.
In contrast, recently vaccinated individuals with a “breakthrough” infection perform better and are better protected, said UCSF immunologist Nadia Roan. This so-called “hybrid immunity” – generated by our original vaccine and the subsequent Omicron infection – is superior and can help fight off future variants.
Breakthrough infections in vaccinated individuals are becoming more common. Before omicron, they accounted for less than 1% of cases. Now even people with four shots are experiencing infections.
This is probably because these new subtypes are evading our immunityy from the vaccines built around the original alpha variant. Each generation outperforms the previous one: BA.2 quickly overtook BA.1 with 30% increased portability. Now BA.2.12.1 outperforms BA.2 with a 25% higher transfer rate, according to Dr. Eric Topol, director of the Scripps Research Translational Institute in La Jolla.
“This foretells his continued rise to dominance in the US over the coming days and weeks,” Topol wrote. It remains to be seen whether newer subtypes named BA.4 and BA.5 can displace BA.2.12.1.
BA.2.12.1 acts almost like another virus due to its evasion ability. According to Linfa Wang, a bat coronavirus researcher at Duke-NUS Medical School in Singapore, “it should be called SARS-3.”
Although we don’t know what future variants will look like, “they will likely become more and more able to evade the immune system,” Kristian Andersen, a scientist at Scripps Research, told Science magazine.
With so many people around the world harboring some level of immunity, the virus is being forced to constantly reinvent itself, Ott said.
Some people have had two shots, some have had three shots, and some have had four. Many of these vaccinated individuals also had breakthrough infections.
And the immunity is temporary, not rock-solid, she said. It waxes and wanes depending on whether people have been recharged or recently infected.
“We’re in a situation now where we have a very highly personalized landscape of immunity out there,” Ott said. “So now we have a situation where the variants can successfully deal with this very heterogeneous immune landscape.”
According to the UCSF team, an important long-term goal is to develop a more universal vaccine that can work against all future variants of the virus. It would target an evolutionarily “conserved” site in its structure that does not mutate over time. It is also important to find out why immunity is declining and how protection can be made more permanent.
“I think we have to get back to the drawing board,” Ott said.
