Enlarge / A tray of prepared syringes for booster shots of Moderna’s vaccine.
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A COVID-19 booster that targets two versions of the coronavirus in one shot provided stronger and broader protection than the current booster that only targets one version, according to clinical trial results released this week by vaccine maker Moderna .
The results are preliminary and have not been peer-reviewed or published in any scientific journal. But Moderna touted the results as evidence that bivalent or multivalent vaccines – those that target two or more versions of the virus in a single shot – are the way forward for COVID-19 boosters.
Moderna and other vaccine makers have set out to develop boosters that could restore the once exceptionally high level of protection that mRNA-based COVID-19 vaccines originally offered, while protecting against future variants. The first-generation mRNA vaccines were all designed to target the progenitor version of SARS-CoV-2 isolated in Wuhan, China — and they did so quite effectively, showing on the order of 95 percent efficacy against symptomatic disease. But the virus has evolved into variants that can evade vaccine-derived protection. The latest variant, Omicron, significantly reduced the vaccine’s effectiveness against symptomatic disease, although protection against serious disease remains strong. Booster doses of the current vaccine design contribute to protection but do not restore the high levels previously observed. And the virus continues to evolve.
The vaccine manufacturers are therefore testing variant-specific booster vaccinations and combination injections. Moderna and Pfizer/BioNTech — joint makers of the other leading mRNA COVID-19 vaccine — swiftly announced plans for an Omicron-specific vaccine in December before the rapidly developing variant took over the globe. So far, however, early animal data suggest that a booster dose targeting only the Omicron variant may not offer any advantage over current vaccines in protecting against Omicron. As variant-specific vaccine trial data continues to come in, vaccine makers have also been working on combination syringes. Earlier this month, for example, the National Institutes of Health announced the start of a clinical trial (in partnership with Moderna) testing six different booster regimens, four of which involve a combination shot.
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Fresh data
Enlarge / This table shows the levels of neutralizing antibodies against different versions of SARS-CoV-2 (Progenitor, Beta, Omicron and Delta) after either a current boost (mRNA-1273) or a combined boost (mRNA-1273.211)
Moderna now has data on one of its first combination shots, targeting the ancestral strain plus the beta variant. The beta variant was first identified in South Africa and was named a “variant of concern” in December 2020 after showing the ability to evade vaccine-derived immune responses. Although experts initially feared it would trigger an Omicron-like wave of infections, Beta never became widespread in the US and has since been completely supplanted by Omicron.
Still, last year vaccine makers had started working on beta-targeting vaccines. And that work has now proven somewhat useful because Beta shares some of the key mutations to evade protective antibodies found in Omicron. Thus, combination vaccines targeting beta may anticipate benefits that Omicron-targeted combination vaccines may have in the future.
New data released by Moderna looked at neutralizing antibody levels in around 300 people who received a 50 microgram dose of the beta/ancestral combo vaccine (dubbed mRNA-1273.211). Antibody levels in this group were compared to those of about 150 people who received the current 50 microgram booster (mRNA-1273), which targets the ancestral version of the virus. Compared to the current booster dose, the Beta/Ancestral combo syringe produced higher levels of neutralizing antibodies to Ancestral virus and the Beta, Omicron and Delta variants. In the case of omicron, the combination syringe produced neutralizing antibody levels twice that of the current syringe (when comparing geometric mean titers). This dual benefit was maintained at six months. In addition, there were no safety concerns with the combination vaccine during the study and the side effect profile looked about the same as that of the current booster dose.
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fall strategy
Of course, this study has limitations. The number of people in the study was not huge, and the study is not large enough to examine the effectiveness of the vaccine. The study also does not look at other types of immune responses, such as B. cell-based responses. However, it strongly suggested that a bivalent vaccine could outperform the current vaccine, as neutralizing antibody levels tend to correlate with protection. The study authors speculated that the additional virus targets contained in the combination vaccine induce “further maturation and evolution” of antibody responses in vaccinated individuals. “Hence, immunization with the primary series does not place an upper limit on the neutralizing antibody response,” they wrote, “and a booster dose of the bivalent vaccine elicits a robust response with titers likely to be protective against COVID-19.”
In a statement, Moderna CEO Stéphane Bancel said the results boosted the company’s optimism for combination shooting. “We believe these results validate our bivalent strategy that we announced and initiated in February 2021. The results show that mRNA 1273.211 [the combo shot] at the 50 µg dose, they induced stronger antibody responses than the 50 µg mRNA-1273 [current] booster vaccine, even if additional variants of concern were not included in the booster vaccine,” Bancel said.
With their strategy for future boosters, Moderna expects to provide re-formulated boosters for fall. However, Bancel anticipates that an Omicron/Ancestral combo booster will provide even stronger and more comprehensive protection.
“Our newest bivalent booster candidate, mRNA-1273.214, which combines Moderna’s currently approved COVID-19 booster with our omicron-specific booster candidate, remains our lead candidate for the Northern Hemisphere booster in fall 2022,” said Bancel. “We look forward to sharing initial mRNA-1273.214 data later in the second quarter. We believe that a bivalent booster vaccine, if approved, would create a new tool as we continue to respond to new variants.”