BA.2.12.1 poised to become dominant in US, raising concern for future vaccines

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A medical worker arranges nucleic acid samples at a makeshift nucleic acid testing site on May 3, 2022 in Beijing, China.
Enlarge / A medical worker arranges nucleic acid samples at a makeshift nucleic acid testing site on May 3, 2022 in Beijing, China.

The omicron subvariant BA.2.12.1 is poised to become dominant in the US, currently accounting for an estimated 36.5 percent of all US SARS-CoV-2 cases, according to the latest estimates released Tuesday by the Centers for Disease Control and Prevention.

The subvariant’s ascent is the latest rapid succession of omicron subvariants, from the sky-scraping peak of cases from the initial omicron subvariant BA.1 in January, to the current bump driven by the subvariant BA.2, which achieved dominance in March. As before, the reason for the viral usurping is that omicron subvariants continue to evolve advantages: BA.2.12.1 has a transmission advantage over BA.2, which had a transmission advantage over BA.1, which had a significant advantage over delta.

The imminent reign of BA.2.12.1 raises concern for yet another wave of infections and poses questions about how effective future omicron-specific vaccines could be against symptomatic infections.

The good news, so far, is that current vaccines are still strongly protecting against severe COVID-19, and BA.2.12.1 does not appear to cause more severe disease than BA.1 or BA.2—though the CDC and other health experts are actively monitoring this. However, the subvariant seems able to evade immune protections, particularly those from prior BA.1 infections.

Evasion

In preliminary data posted online Monday, researchers in Beijing found that BA.2.12.1 showed “strong neutralization evasion” against antibodies from vaccinated people who had also had breakthrough BA.1 infections. In the study, participants had been vaccinated with Sinovac’s CoronaVac vaccine, an inactivated whole virus vaccine, which had about 50 percent efficacy in early observational studies in Brazil. (mRNA-based vaccines demonstrated efficacy rates around 95 percent in initial clinical trials.)

The researchers looked at neutralizing antibodies from 50 people who had received three CoronaVac doses and recovered from a BA.1 infection. Comparing neutralizing antibody levels over a range of coronavirus variants, researchers found that neutralizing antibody levels against BA.2 were about 1.86 times lower than they were for BA.1. But, things got worse as researchers moved on to newer subvariants: Neutralizing antibody levels were 3.73 times lower for BA.2.12.1, compared with BA.1, and eight times lower against BA.4 and BA.5.

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The latter finding echoes that of preliminary data out of South Africa, which Ars reported Monday. There, researchers found that in unvaccinated people who had recovered from a BA.1 infection, neutralizing antibody levels were 7.6 fold and 7.5 fold lower against BA.4 and BA.5, respectively, compared with levels against BA.1. While vaccination with either a Pfizer/BioNTech vaccine or a J&J vaccine narrowed the gap in neutralizing antibody levels, researchers still saw a loss in protection: 3.6 fold and 2.6 fold lower neutralizing antibody levels against BA.4 and BA.5, respectively, compared with BA.1.

Together, the data all point to the possibility of more reinfections from newer omicron subvariants, particularly in people who are unvaccinated or not up to date on their vaccinations. This could drive yet more waves of infections in the US and around the world—though experts don’t expect another towering wave like the BA.1 surge in January.

Concerns

It also raises concerns about the designs of second-generation vaccines—some of which may target BA.1, at least in part. For instance, last month, Moderna, announced that it believed a bivalent vaccine—targeting two version of the virus in one shot—would be a winning strategy to provider broader, longer-lasting protection.

“Our latest bivalent booster candidate, mRNA-1273.214, which combines the currently authorized Moderna COVID-19 booster with our [BA.1] omicron-specific booster candidate, remains our lead candidate for the fall 2022 Northern Hemisphere booster,” Moderna CEO Stéphane Bancel said in a statement at the time.

But, the new data suggests BA.1-based vaccines may offer weak protection against BA.2, BA.4, BA.5, and any other omicron subvariants down the line.

“Unlike when omicron first appeared, now omicron sublineages have started to target the humoral immunity [antibodies and other adaptive responses] induced by omicron itself, including the humoral immunity induced by post-vaccination omicron infection,” the authors of the new study from Beijing write. “This poses a great challenge” to establishing protection and “suggests that omicron BA.1-based vaccine may not be the ideal antigen for inducing broad-spectrum protection against emerging omicron sublineages.”

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