A total of seven coronavirus disease 2019 (COVID-19) vaccines have been approved for Emergency Use by the World Health Organization (WHO) to date, two of which are adjuvanted inactivated virus vaccines. CoronaVac is a WHO-approved inactivated virus vaccine and more than 750 million CoronaVac doses have been administered in over 40 countries worldwide.
Study: A RCT of a third dose CoronaVac or BNT162b2 vaccine in adults with two doses of CoronaVac. Image Credit: rafapress / Shutterstock.com
Poor immunogenicity and antibody waning in CoronaVac recipients
The safety and efficacy of CoronaVac have been evaluated in various age groups, with Phase III randomized clinical trials (RCTs) demonstrating high efficacies against symptomatic COVID-19 and protection against hospitalization and death. Despite these observations, recent breakthrough infections, including the ones with severe disease leading to death in Indonesian adults who received CoronaVac, have raised concern on the efficacy of CoronaVac.
Some studies have shown poor immunogenicity and antibody waning in CoronaVac recipients of; however, there is a lack of data from RCTs that compare the immunogenicity and safety of vaccination schedules with homologous and heterologous vaccines as a booster dose.
A recent observational study showed that CoronaVac had much lower immunogenicity compared to the Pfizer-BioNTech BNT162b2 messenger ribonucleic acid (mRNA) vaccine. Plaque reduction neutralization test titers showed that although most CoronaVac recipients reached protective thresholds one month after receiving the second dose of vaccine, many vaccine recipients exhibited low protective levels in a few months, thus leading to an inevitable waning of antibody titers.
Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are known to reduce vaccine protection and can thus further compromise the effectiveness of CoronaVac. Taken together, these observations emphasize the need for a booster dose of the vaccine. Since it was not clear if the booster should be a homologous or heterologous vaccine, a head-to-head comparison between the CoronaVac and Pfizer COID-19 vaccines in an unbiased experimental setting was performed.
Comparing the safety and immunogenicity of Pfizer and CoronaVac booster doses
A recent study published on the preprint server medRxiv* reports the results of an RCT comparing the immunogenicity and safety of BNT162b2 and CoronaVac as the third dose in adults with poor antibody response to two doses of the CoronaVac.
In the current study, the researchers randomly chose adults who had received two CoronaVac doses and had a low antibody response to administer the third dose of either the BNT162b2 or CoronaVac vaccine. Local and systemic adverse reactions after the booster dose were recorded, along with measurements of SARS-CoV-2 neutralizing and spike binding antibodies levels in the plasma.
BNT162b2 booster vaccine induced significantly higher levels of neutralizing antibodies than CoronaVac booster
The findings from the current study showed that one month after receiving the booster vaccine dose, BNT162b2 vaccine recipients exhibited significantly higher spike receptor binding, surrogate virus neutralization, spike nucleocapsid (N) terminal domain binding, and spike S2 domain binding levels as compared to those who received the CoronaVac booster dose.
Adverse reactions such as injection site pain and swelling, fatigue, and muscle pain were reported more in the BNT162b2 group as compared to the CoronaVac group. The mean results of the surrogate virus-neutralizing test (sVNT) against the wild-type virus and the Beta, Gamma, and Delta variants in the BNT162b2 booster vaccine group was 96.83%, 92.29%, 92.51%, and 95.33%, respectively, as compared to 57.75%, 38.79 %, 32.22%, and 48.87%, respectively, in participants who received CoronaVac as a third dose. This shows a significantly higher response elicited by the BNT162b2 booster vaccine.
“While both vaccines resulted in boosting neutralizing and spike binding antibody levels, BNT162b2 led to markedly higher levels of antibody compared to those boosted with CoronaVac.”
According to the authors, their study is the first RCT to compare the efficacy of BNT162b2 and CoronaVac as the booster dose for COVID-19 vaccination. They monitored the immune response to the booster vaccine longitudinally starting from pre-vaccination in an age-matched cohort.
The findings of this RCT demonstrate that the BNT162b2 booster dose is significantly more immunogenic than a CoronaVac booster in people with poor response to the previous CoronaVac vaccination. The BNT162b2 vaccine also induces higher levels of SARS-CoV-2 specific antibodies to different SARS-CoV-2 variants of concern. The adverse reactions to the booster dose were mild and short-lived.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.