BA.2.12.1 is on the verge of becoming dominant in the United States, raising concerns for future vaccines

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

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

The ascent of the sub-variant is the last rapid succession of omicron sub-variants, from the sky-scraping case peak of the initial omicron BA.1 sub-variant in January, to the current bump driven by the BA sub-variant .2, which achieved dominance in March. As before, the reason for viral spoofing is that the omicron subvariants continue to develop 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 concerns about a new wave of infections and raises questions about the effectiveness of future omicron-specific vaccines against symptomatic infections.

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

Escape

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

The researchers examined the neutralizing antibodies of 50 people who had received three doses of CoronaVac and recovered from a BA.1 infection. By comparing levels of neutralizing antibodies across a range of coronavirus variants, the researchers found that levels of neutralizing antibodies against BA.2 were approximately 1.86 times lower than those for BA.1. But things got worse when the researchers moved on to new subvariants: Neutralizing antibody levels were 3.73 times lower for BA.2.12.1, compared to BA.1, and eight times lower against BA.4 and BA.5.

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

Taken together, the data all point to the possibility of more reinfections with the new omicron subvariants, especially in people who are unvaccinated or not up to date with their vaccinations. This could lead to even more waves of infections in the United States and around the world, although experts do not expect another towering wave like the BA.1 surge in January.

Concerns

It also raises concerns about the design of second-generation vaccines, some of which may target BA.1, at least in part. For example, last month Moderna announced that it believed a bivalent vaccine – targeting two versions of the virus at once – would be a winning strategy to provide broader, longer-lasting protection.

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

But, the new data suggests that 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, omicron sublines have now begun to target humoral immunity [antibodies and other adaptive responses] induced by omicron itself, including humoral immunity induced by post-vaccination infection with omicron,” write the authors of the new Beijing study. “This poses a great challenge” to the establishment of protection and “suggests that the omicron BA.1-based vaccine may not be the ideal antigen to induce broad-spectrum protection against emerging omicron sublines.”

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