Safety and immunogenicity of inactive vaccines as booster doses for COVID-19 in Türkiye: A randomized trial

ABSTRACT

Protective neutralizing antibody titers reduce in time after COVID-19 vaccinations, as in individuals who have had COVID-19. This study aimed to evaluate the safety and immunogenicity of CoronaVac and TURKOVAC vaccines used as a booster dose after CoronaVac primary vaccination. This double-blind, randomized, controlled, phase II, multicenter study included healthy male and female adults (18–60 years) who were vaccinated with two doses of CoronaVac vaccine and did not exceed the duration of at least 90 days and a maximum of 270 days from the second dose of vaccination. Among 236 eligible volunteers, 222 were recruited for randomization between July 12, 2021 and September 10, 2021; 108 and 114 were randomized to the TURKOVAC and CoronaVac arms, respectively. The primary endpoint was adverse events (AEs) (ClinicalTrials.gov; Identifier: NCT04979949). On day 28, at the neutralizing antibody threshold of 1/6, the positivity rate reached 100% from 46.2% to 98.2% from 52.6% in the TURKOVAC and CoronaVac arms, respectively, against the Wuhan variant and the positivity rate reached 80.6% from 8.7% in the TURKOVAC arm vs. 71.9% from 14.0% in the CoronaVac arm against the Delta variant. IgG spike antibody positivity rate increased from 57.3% to 98.1% and from 57.9% to 97.4% in the TURKOVAC and CoronaVac arms, respectively. The TURKOVAC and CoronaVac arms were comparable regarding the frequency of overall AEs. Both vaccines administered as booster yielded higher antibody titers with acceptable safety profiles.

Plain Language Summary

What is the context?

• The timing of the primary and booster doses for each vaccine differs.

• We aimed to evaluate the safety and immunogenicity of CoronaVac and TURKOVAC vaccines used as homologous booster dose after CoronaVac primary vaccination.

What is new?

• The neutralizing antibody titers against the Wuhan variant decreased below 1/6- the seropositivity threshold value- in more than 55% of the participants 4 months after administration of two doses of CoronaVac vaccine.

• Immunogenicity was re-stimulated and the neutralizing antibody titers increased rapidly and markedly with the administration of the CoronaVac or TURKOVAC as a booster dose 4 months after the second dose.

• While the increase in neutralizing antibodies against the Wuhan variant was similar with both CoronaVac and TURKOVAC, more antibodies developed against the Delta variant with TURKOVAC.

What is the impact?

• With the Hybrid COV-RAPEL TR study, after the primary vaccination consisting of two doses of inactivated vaccine, antibody titers decreased in the long term; however, higher antibody titers are achieved than the primary vaccination after the booster dose administered after 4–6 month interval.

• Booster application with TURKOVAC provides antibodies at least as much as the CoronaVac booster dose, with an acceptable safety profile.

GRAPHICAL ABSTRACT

KEYWORDS:

• Booster vaccine
• CoronaVac
• COVID-19
• inactive
• TURKOVAC

Acknowledgments

The authors thank the Health Institutes of Türkiye (TUSEB) for funding the study. The authors also thank OMEGA CRO, Ankara, Türkiye for representing TUSEB and for their contribution to the correspondence between the study investigators, the ethics committee, and the Ministry of Health; additionally for performing the monitoring, management of the study sites, storage, and distribution of the consumables, provision of OpenClinica- an open source clinical trial software serving for the purpose of clinical data management and electronic data capture, developing electronic case report forms, the interactive web response system (IWRS), and the interactive voice response system (IVRS) and data management, statistical analyses, and overall project management, and manuscript formatting support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

IA and AK conceptualized and coordinated the study. AO and IA had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. AO, AE, IA, and AK drafted the article. IA and AK revised the manuscript critically for important intellectual content. All authors contributed to the acquisition of data. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Data sharing statement

Anonymous participant data that support the findings of this study are available from the corresponding author upon reasonable request.

Role of the funder

The TUSEB provided funding for the present study; approved the final protocol, the manuscript, and gave permission to submit it for publication, but had no role in data collection, analysis, interpretation, or writing of the manuscript.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2022.2122503.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This study was funded by the Health Institutes of Türkiye (TUSEB).