In a recent study posted to the medRxiv* preprint server, researchers compared the immunogenicity of the reduced and standard doses of the BNT162b2 and messenger ribonucleic acid (mRNA)-1273 vaccine in adults immunized with two doses of CoronaVac (CV)-vaccine.
Study: Comparison of the reactogenicity and immunogenicity of a reduced and standard booster dose of the mRNA COVID-19 vaccine in healthy adults after two doses of inactivated vaccine. Image Credit: Tobias Arhelger/Shutterstock
This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources
Background
Amid a shortage of vaccines in countries such as Thailand, resulting in delays in the vaccination schedule, a dose reduction strategy could help them save costs on the imported vaccine and distribute vaccine more quickly during the coronavirus disease 2019 (COVID-19) outbreak. Moreover, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants of concern (VOCs) continue to cause breakthrough infections among vaccinated individuals in countries with high vaccination coverage.
Although in one of their previous study, the authors of the current study demonstrated that individuals who received inactivated vaccines (as primary vaccination series) achieved a high immune response against SARS-CoV-2 Delta and Omicron VOCs following booster vaccination with the standard dose of BNT162b2 or mRNA-1273.
However, it is unknown whether a reduced booster dose after the inactivated vaccine primary series could induce adequate anti-SARS-CoV-2 immunity against the Delta and Omicron VOCs.
About the study
In the current prospective cohort study, researchers included Thai adults over 18 years of age without COVID-19 history immunized with two doses of CV vaccines.
Six months (± one month) after the second dose, the study participants consented to receive a reduced booster dosage, i.e., a booster dosage of 15 μg-BNT162b2 or 50 μg-mRNA-1273 vaccines between November and December 2021. The control cohort included individuals who received the standard dose of these two vaccines between September and December 2021.
The reduced and standard doses of the BNT162b and mRNA-1273 vaccines contained 15μg (reduced), 30μg (standard), and 50μg (reduced), 100μg (standard) doses, respectively. In all, there were four study groups, two receiving reduced doses of BNT162b and mRNA-1273 vaccines, and the other two receiving standard doses of the same two vaccines.
They collected blood samples of all the study participants before vaccination (day 0, baseline) and after receiving the booster dose and analyzed them using a surrogate virus neutralization test (sVNT). Specifically, they evaluated total immunoglobulin (Ig) specific to SARS-CoV-2 nucleoprotein (N) and receptor-binding domain (RBD). Further, they used a heparinized whole blood sample to assay the interferon-gamma (IFN-γ) SARS-CoV-2 releasing T cell response.
The researchers also monitored test subjects for local, systemic, and any adverse events following immunization (AEFIs) occurring within seven days of administrating the booster dose. AEFIs were analyzed using the risk difference with a 95% confidence interval (CI).
They used the Chi-square test to analyze the age and sex of study participants. Lastly, they used a non-parametric Kruskal–Wallis or Wilcoxon signed-rank test with multiple comparison adjustments to calculate differences in antibody titers, SARS-CoV-2 index (S/C), and percentage inhibition between groups, where a p-value of <0.05 was considered statistically significant.
Study findings
The study included 222 healthy participants, of which 110 participants received the reduced vaccine doses, and 112 participants received the standard vaccine doses. The authors noted no significant differences in age and sex between all the four study groups.
The 'injection site pain' was the most common solicited AEFI among all groups. While the authors observed more frequent headache, myalgia, joint pain, and diarrhea in the 15μg- than the 30μg-BNT162b2 groups, chilling and joint-pain were more frequent in the 100μg- than the 50μg-mRNA-1273 groups; however, they observed no severe AEFIs in any of these groups.
Among the recipients of reduced and standard doses of the same mRNA vaccine, the authors observed no significant differences in Ig and IgG anti-RBD levels; and most participants, more than 94%, were IgG anti-N seronegative after receiving the mRNA vaccines.
The geometric mean titers (GMTs) of total Ig and IgG anti-RBD between the four study groups were similar initially at baseline. At the second visit, individuals vaccinated with 15μg-, 30μg-, 50μg-, and 100μg of mRNA-1273 had total Ig anti-RBD levels of 28,413, 31,793, 41,171, and 51,979 U/mL, respectively. These titers were reduced slightly by the third visit.
Of 160 participants evaluated for sVNT against the Delta and Omicron VOCs, the percentage seropositivity on the first visit was 0.08% and 0.03% for the Delta and Omicron, respectively. Over 97% of sera samples from all four groups inhibited the Delta strain by the third visit. In comparison, sera from the 30 μg-BNT162b2 group inhibited Omicron VOC slightly lesser than the sera from other groups.
QuantiFERON assay results showed that the average IFN-γ CD4+ and CD8+ T cell counts were higher in all groups at the second visit than at baseline; however, by the third visit, these T cell counts slightly reduced. Importantly, T cell counts between participants receiving the reduced and standard booster doses of each vaccine were similar.
Conclusions
To conclude, the study findings demonstrated that administration of both the reduced and standard doses of the BNT162b2 and mRNA-1273 COVID-19 vaccines elicited similar levels of neutralizing antibodies in individuals who had received two doses of inactivated CV vaccine even against the SAR-CoV-2 Delta and Omicron VOCs. Additionally, a few participants had detectable anti-N IgGs at baseline.
Together, these findings could inform the decision-making authorities regarding the use of reduced mRNA vaccine booster doses in healthy adults already immunized with CV.
This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources
Article Revisions
- May 11 2023 - The preprint preliminary research paper that this article was based upon was accepted for publication in a peer-reviewed Scientific Journal. This article was edited accordingly to include a link to the final peer-reviewed paper, now shown in the sources section.
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