Comparing reactogenicity of COVID-19 vaccine boosters: a systematic review and meta-analysis

ABSTRACT

Introduction

Different COVID-19 vaccines are being utilized as boosters. This systematic review and meta-analysis aims to evaluate the reactogenicity of COVID-19 vaccines given as booster doses, according to vaccine type, dose, timing, participant characteristics and primary immunization regimen received.

Methods

Four databases (MEDLINE, Embase, Web of Science and CENTRAL) were searched for randomized controlled trials between 1 January 2020 and 1 January 2023 according to predetermined criteria.

Results

Twenty-eight studies describing 19 vaccines of four different types (viral vector, inactivated, mRNA and protein sub-unit) were identified. BNT162b2 vaccine (Pfizer-BioNTech) was selected as the control as it was most often compared with other vaccines. Fever, fatigue, headache, injection-site pain, redness, and swelling were the most frequently reported solicited events. mRNA vaccines were the most reactogenic, followed by viral vector vaccines and protein sub-unit vaccines, while inactivated vaccines were the least reactogenic. Full-dose vaccines were more reactogenic than half-dose vaccines. Heterologous BNT162b2 boosters were more reactogenic than boosters with the same vaccine used for primary immunization.

Conclusions

COVID-19 vaccine booster schedules have distinct reactogenicity profiles, dependent on dose and vaccine type, which may allow targeted recommendations and provide choice for specific populations. Greater standardization of adverse event reporting will aid future studies.

KEYWORDS:

• Systematic review
• meta-analysis
• COVID-19 vaccine boosters
• reactogenicity
• adverse events

Article highlights

• The majority of booster vaccine trials compared COVID-19 vaccines against each other; placebo-controlled trials were rare.

• Four main vaccine types were used as booster doses: mRNA vaccines were most reactogenic, followed by viral vector vaccines, protein sub-unit vaccines and inactivated vaccines.

• Of the mRNA vaccines, 100ug (full dose) of mRNA-1273 was more reactogenic than 30ug of BNT162b2, but comparable when used at half-dose (50ug).

• Compared to BNT162b2 (30ug), adenovirus-vector vaccines had an increased rate of fever but a lower rate of local adverse events while protein sub-unit vaccines had lower rates of pain and swelling at the injection site.

• Inactivated vaccines had lower risks of local and systemic adverse events compared to BNT162b2.

• Homologous boosters with the same vaccine received for primary immunization were less reactogenic than heterologous BNT162b2 boosters.

• Reporting of solicited adverse events on vaccine trials is inconsistent, with differences in number and type of symptoms reported. This lack of standardization of reporting makes comparison of different vaccines challenging.

• Vaccines with lower rates of reactogenicity may be preferable in specific settings and populations.

Declaration of interest

PT Heath coordinates research on behalf of St Georges, University of London, which is funded by vaccine manufacturers, including those that manufacture COVID-19 vaccines (Pfizer, AZ, Novavax, Moderna, Valneva, Janssen). He is also a member of the UK Joint Committee on Vaccination and Immunization (JCVI). The authors have no other 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 apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have received honoraria for their review work. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14760584.2024.2315089

Data availability statement

Study data is available via reasonable requests directed to the corresponding author.

Author contributions

ASFR, PH, YH, DS, TBR and CLS conceptualized and designed the work. ASFR, TBR and CLS carried out the database search and identified eligible studies. ASFR, DS, TBR, TM, NT and CLS performed risk of bias assessments and data extraction. Tables and figures were created by ASFR. Data analysis and interpretation was performed by ASFR, guided by JH and PH. ASFR and PH drafted the manuscript. All authors contributed to, reviewed, and approved the final manuscript.

Acknowledgments

We thank the library team at St George’s University of London for their input during the data search.

We would like to thank the core members of the COV-BOOST trial team (Saul Faust, Xinxue Liu, Victoria Cornelius, Leila Janani, Alasdair P. S. Munro) and the Oxford Vaccine Group team (Sue Ann Costa Clemens, Andrew J. Pollard) for facilitating access to adverse event data from their trials to be included in this review.

Additional information

Funding

This paper was not funded.