Reasons the bivalent COVID-19 vaccines have not shown a substantial advantage in research and clinical settings are explored in a Perspective article by Paul Offit, MD, noted pediatrician and vaccinologist who currently serves on the FDA’s Vaccines and Related Biological Products Committee. “Although boosting with a bivalent vaccine is likely to have a similar effect as boosting with a monovalent vaccine, booster dosing is probably best reserved for the people most likely to need protection against severe disease — specifically, older adults, people with multiple coexisting conditions that put them at high risk for serious illness, and those who are immunocompromised,” Offit writes. “In the meantime, I believe we should stop trying to prevent all symptomatic infections in healthy, young people by boosting them with vaccines containing mRNA from strains that might disappear a few months later.”
The strategy for significantly increasing BA.4 and BA.5 neutralizing antibodies using a bivalent vaccine may have failed because of imprinting, Offit maintains: “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. 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. This effect could possibly be moderated by immunizing people either with BA.4 and BA.5 mRNA alone or with a greater quantity of BA.4 and BA.5 mRNA. Evidence in support of these strategies can be found in Pfizer–BioNTech’s data regarding its BA.1-containing bivalent vaccine, which showed that BA.1-specific neutralizing-antibody responses were greater in persons who were injected with a monovalent vaccine containing 30 μg or 60 μg of BA.1 mRNA or a bivalent vaccine containing 30 μg of BA.1 mRNA and 30 μg of ancestral-strain mRNA than in those who received a bivalent vaccine containing 15 μg of each type of mRNA.”