The study is currently available on the medRxiv* preprint server.
Background
The continuous emergence of novel SARS-CoV-2 variants with improved immunologic fitness has raised global concern about the possibility of declining efficacy of currently available COVID-19 vaccines that are based on the original Wuhan strain of SARS-CoV-2. Moreover, recent evidence on vaccine breakthrough cases has further highlighted the possibility of waning vaccine immunity with time. Given these possibilities, some countries have decided to immunize at-risk populations with a third booster dose of the COVID-19 vaccine.
Studies conducted in real-world setups have demonstrated improved antiviral effectiveness of heterologous prime-boost COVID-19 vaccination programs that most commonly include mRNA-based and adenoviral vector-based vaccines. A booster vaccination with mRNA-based vaccines has shown high immunogenicity even with reduced dosage.
In the current study, the scientists have investigated the safety and immunogenicity of three types of booster vaccines in healthy adults who had previously received two primary doses of ChAdOx1 or CoronaVac vaccine.
Study design
A total of 352 healthy adults (age range: 18 – 60 years) were enrolled for the study. Of them, 179 had received two doses of CoronaVac vaccine at an interval of four weeks, and 173 had received two doses of ChAdOx1 vaccine at an interval of eight to ten weeks.
Three types of booster vaccines were evaluated in the study, including inactivated vaccine BBIBP-CorV (Sinopharm), ChAdOx1,and BNT162b2 (full dose of 30 µg and half dose of 15 µg). The booster dose was administered eight to twelve weeks after primary vaccination.
Safety profile of booster vaccination
Among participants with CoronaVac primary vaccination, the highest levels of local adverse reactions were observed after the adenoviral vector booster vaccine (ChAdOx1), followed by the high-dose mRNA vaccine (BNT162b2), low-dose mRNA vaccine (BNT162b2), and inactivated BBIBP-CorV vaccine.
Among participants with ChAdOx1 primary vaccination, the highest levels of local adversities were observed after high-dose mRNA booster vaccine, followed by low-dose mRNA vaccine, adenoviral vector vaccine, and inactivated vaccine.
A similar trend was observed for systemic adverse reactions. All adversities observed after booster vaccination were mild or moderate in severity and resolved within two to three days. No serious adverse reactions were observed among participants.
Humoral immunity after booster vaccination
All participants were tested for seropositivity before booster vaccination. About 97% of CoronaVac-vaccinated participants and 99% of ChAdOx1-vaccinated participants showed seropositivity. However, the average titer of anti-spike receptor-binding domain (RBD) antibodies was comparatively lower among participants with CoronaVac primary vaccination.
Among participants with CoronaVac primary vaccination, the highest level of anti-RBD antibodies two weeks after booster vaccination was observed in response to the high-dose mRNA vaccine, followed by the low-dose mRNA vaccine, adenoviral vector vaccine, and inactivated vaccine. Overall, the booster doses of high-dose and low-dose mRNA vaccines, adenoviral vector vaccine, and inactivated vaccine respectively caused a 154-fold, 105-fold, 35-fold, and 4-fold induction in antibody titers compared to baseline values.
Among participants with ChAdOx1 primary vaccination, the induction in antibody levels after booster dose followed the same trend as participants with CoronaVac primary vaccination. The booster doses of high-dose and low-dose mRNA vaccines, adenoviral vector vaccine, and inactivated vaccine caused a 25-fold, 21-fold, 2-fold, and 1-fold induction in antibody titers compared to baseline values, respectively. For all tested vaccines, a comparatively lower antibody level after booster dose was observed in ChAdOx1-vaccinated participants.
Neutralization of SARS-CoV-2 variants
Among participants with CoronaVac primary vaccination, the highest neutralizing antibody titers against the delta variant were observed after booster vaccination with low-dose mRNA vaccine, followed by high-dose mRNA vaccine, adenoviral vector vaccine, and inactivated vaccine. In contrast, the highest neutralizing titers against delta variant in ChAdOx1-vaccinated participants were observed after booster vaccination with a high-dose mRNA vaccine.
A similar trend was observed for neutralizing antibody titers against the beta variant. Considering all primary vaccine types and viral variants, no significant difference in neutralizing titers was observed between high-dose and low-dose mRNA booster vaccines.
Interferon-gamma response
About 35% of ChAdOx1-vaccinated participants and 25% of CoronaVac-vaccinated participants showed positive interferon-gamma response prior to booster vaccination. Among participants who were seronegative at baseline, the highest interferon response was observed after booster vaccination with high-dose mRNA vaccine.
Study significance
The study reveals that a booster dose of mRNA-based COVID-19 vaccine has the highest immunogenicity among individuals who have received two primary doses of adenoviral vector vaccine or inactivated vaccine. Based on the study findings, the scientists suggest that a lower dose of mRNA-based COVID-19 vaccine might be used as a booster in countries with low vaccine supply.
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