A third dose of an mRNA COVID-19 vaccine is necessary to give someone robust neutralizing antibody activity against the Omicron variant, according to data from Emory researchers posted on the preprint server Biorxiv.
The findings support public health efforts to promote booster vaccination as a measure to fight Omicron, which is currently overwhelming hospitals around the world. They also explain why more breakthrough infections are occurring with the Omicron variant in people who have been vaccinated twice, and are in line with what other investigators have observed.
Compared with the 2020 Wuhan strain, the Omicron variant of SARS-CoV2 has more than 30 mutations in the viral spike protein, which is the primary target of neutralizing antibodies generated by vaccination.
“Our findings highlight the need for a third dose to maintain an effective antibody response for neutralizing the Omicron variant,” says lead author Mehul Suthar, a virologist based at Emory Vaccine Center and Yerkes National Primate Research Center.
Vaccinated individuals who develop breakthrough Omicron infections are likely to experience less severe symptoms, and it is possible for Omicron to infect people even after receiving a booster, Suthar notes. Still, a majority of patients now coming into hospitals continue to be those who are unvaccinated.
In the preprint, Emory researchers tested blood samples from people who participated in Pfizer/BioNTech or Moderna vaccine studies in the laboratory for their ability to smother SARS-CoV-2 variants in culture. The preprint does not include clinical outcomes from infection, and also does not cover other aspects of vaccine-induced antiviral immunity, such as T cells.
In people who were vaccinated twice with mRNA vaccines, either Pfizer/BioNTech or Moderna, none showed measurable neutralizing antibody activity against Omicron six months after vaccination. But 90 percent displayed some neutralizing activity against Omicron a few weeks after a third dose.
The level of neutralizing antibody activity against Omicron in boosted individuals was reduced more then ten-fold compared to the reference point of the 2020 strains. People who had COVID-19 in 2020 and then were vaccinated twice afterwards had an intermediate level of antibodies: 55 percent retained some neutralizing activity against Omicron.
The Beta variant, initially identified in South Africa in 2020, was also tested for comparison in the preprint. Beta is somewhat more resistant to vaccine-induced immunity and deadlier, compared with the reference Wuhan or Washington state strains, but lost out in 2021 compared with the more transmissible Delta strain.
The first author is postdoc Venkata Viswanadh Edara in Suthar’s lab. Co-authors include immunologist Jens Wrammert, clinicians Evan Anderson and Nadine Rouphael, who are principal investigators for vaccine study sites at Emory, and Daniel Douek at the National Institute of Allergy and Infectious Disease’s Vaccine Research Center.
Disclosure: Suthar serves on the advisory boards for Moderna and Ocugen. His lab also contributed to a NIAID/Duke preprint on the same topic.