Catherine Kwon

A recent Yale study suggests that a popular COVID-19 vaccine authorized for use in 48 countries offers little protection on its own against the Omicron variant. 

After working with public health officials in the Dominican Republic, Yale researchers have determined that the standard two dose course of Sinovac’s CoronaVac vaccine produced no neutralizing antibodies against the Omicron variant. However, administering a messenger RNA, or mRNA, booster dramatically increased antibody levels. These results come from a manuscript recently published in the journal Nature Medicine after analyzing the blood samples of 101 adults in the Dominican Republic. 

“We found that mRNA booster vaccination in people who were immunized with two doses of CoronaVac, an inactivated SARS-CoV-2 vaccine, significantly elevated neutralizing antibodies to the ancestral, Delta and Omicron variants of concern,” Akiko Iwasaki, professor of immunobiology and epidemiology at the Yale School of Medicine and senior author of the paper, wrote in an email. 

The CoronaVac vaccine is manufactured by the Chinese pharmaceutical company Sinovac Biotech. As of October 2021, CoronaVac was the most widely used COVID-19 vaccine in the world, with just under 2 billion doses administered.

Unlike the mRNA technology of the Pfizer-BioNTech and Moderna vaccines popular in the United States, CoronaVac utilizes an inactivated SARS-CoV-2 virus to induce an immune response. 

“The Sinovac vaccine uses a whole virus that has been chemically inactivated so it is not able to infect cells or induce disease,” explained Valter Silva Monteiro, a doctoral student in immunobiology at the Yale School of Medicine and a co-lead author of the paper. “The inactivated virus will be eaten by the immune cells. These cells will process the virus and show parts of the viral proteins to lymphocytes that produce molecules called antibodies, which recognize the virus if the body encounters it again.”

The data presented in this article comes from a cohort of 101 adults in the Dominican Republic vaccinated with the standard two dose regimen of CoronaVac. These patients were then administered a booster dose of the Pfizer-BioNTech mRNA vaccine. Blood serum samples were analyzed for neutralizing antibodies at three distinct time points — just before, seven days after and 28 days following the booster dose. 

Prior to administration of the Pfizer-BioNTech booster, none of the patients in the study produced neutralizing antibodies against the Omicron variant. Four weeks after the booster, however, 80 percent of the cohort had developed these antibodies. 

“The levels of neutralizing antibodies induced by this heterologous prime boost strategy were 1.4 times higher than the levels obtained by mRNA two dose vaccines,” Iwasaki wrote. “In addition to neutralizing antibodies, memory T and B cells, as well as non-neutralizing antibodies contribute to preventing disease from Omicron.”

While the researchers were encouraged by these results, the study also underscored the immune escape properties of the Omicron variant. Results indicate that the vaccine-induced levels of neutralizing antibodies against Omicron post-Pfizer-BioNTech booster were 7.1- and 3.6-fold lower compared to the ancestral and Delta variants, respectively.  

“The Omicron variant has a greater antibody escape when compared with the other variants of concern, or VOC,” Silva Monteiro noted. “Despite the increased viral neutralization levels after the booster, they are still significantly reduced compared to the other VOC.” 

The authors of the study emphasized the global need for booster vaccines in order to limit the impact of variants. The findings provided strong supporting evidence for the effectiveness of a heterologous prime boost strategy, an emerging approach in which inactivated virus vaccines are followed by mRNA boosters.

Already, the findings of this study have resulted in key changes in public health strategies abroad.

“In the Dominican Republic, due to the convincing data of this collaborative study with Yale University, we are recommending a heterologous booster in people who already have two doses of the other vaccines available in the country,” Eddy Pérez-Then, a member of the Dominican Republic Health Cabinet and the principal investigator of the study, wrote in an email. “The government of the Dominican Republic has acquired sufficient mRNA vaccines to cover the demand, including the 4th booster dose in persons who require it.”

Looking ahead, Yale researchers are collaborating with investigators in Brazil to examine the feasibility of other heterologous booster strategies to further protect patients that initially received inactivated virus vaccines.

However, researchers have cautioned that the results of this study do not necessarily tell the whole story. 

“The observed laboratory findings must be correlated with clinical data,” Pérez-Then wrote. “Although the lab suggests an association between vaccine efficacy against specific variants, in the real world we are identifying that the clinical-epidemiological behavior does not correlate 100% with what is observed in-vitro.”

Sinovac’s CoronaVac received an emergency use listing from the World Health Organization on June 1, 2021.