Reactogenicity, immunogenicity, and humoral immune response dynamics after the third dose of heterologous COVID-19 vaccines in participants fully vaccinated with inactivated vaccine

ABSTRACT

Introduction

Immunogenicity after the CoronaVac vaccine remains uncertain, especially regarding infections with the coronavirus variants of concern and waning immunity.

Methods

This was a single-center, open-label clinical trial designed to assess the immunogenicity and safety of BBIBP-CorV, AZD1222, or BNT162b2 as the third vaccination. The key eligible criteria were individuals at least 18 years old who were fully vaccinated with two doses of CoronaVac vaccine for 2–4 months. The primary endpoint was the ratio of the geometric mean concentration (GMC) of the total anti-receptor binding domain (RBD) antibody post-vaccination compared with that pre-vaccination. The secondary endpoint was reactogenicity within 7 days.

Results

Forty-one participants received AZD1222, 40 received BBIBP-CorV, and 40 received BNT162b2. The GMC of anti-RBD antibody at 2 weeks post-vaccination was 31,138.67 binding antibody units (BAU)/mL for BNT162b2, 6,412.10 BAU/mL for AZD1222, and 1,092.7 BAU/mL for BBIBP-CorV. Compared with pre-vaccination, the ratio of anti-RBD concentration was 690.24 for BNT162b2, 130.02 for AZD1222, and 17.79 for BBIBP-CorV. No potentially life-threatening adverse reaction were observed within 7 days.

Conclusion

A third vaccination with the heterologous vaccine, BBIBP-CorV, AZD1222, or BNT162b2, can elicit a robust immune response, without serious adverse events in participants fully vaccinated with the CoronaVac vaccine.

KEYWORDS:

• AZD1222
• ChAdOx1
• BBIBP-CorV
• BNT162b2
• booster dose
• third dose
• immunogenicity
• reactogenicity

Acknowledgments

We thank the clinical research management unit, Chulabhorn Royal Academy, for managing this project. We also thank the central laboratory of Chulabhorn Hospital for laboratory testing. We gratefully acknowledge funding from Chulabhorn Royal Academy and National Vaccine Institute. We thank Charles Allan, PhD, and Melissa Crawford, PhD, from Edanz (https://www.edanz.com/ac) for editing a draft of this manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

KT conceptualized and designed the study, data collection, analysis and interpreted the data, drafted the manuscript, revised, and approved the final manuscript as submitted. TS, TP, and KS participated in the conceptualization and design of the study, participated in data collection, analysis, and interpretation of the data, revised the article, and approved the final article as submitted. KW, NT, and GS participated in the conceptualization and design of the study, participated in data collection, critically reviewed the manuscript, and approved the final manuscript as submitted. NM and CA conceptualized and designed the study, coordinated, and supervised data collection, critically reviewed the manuscript, and approved the final manuscript as submitted.

Additional information

Funding

This study was funded by the Chulabhorn Royal Academy and National Vaccine Institute, Thailand.