Nasikarn Angkasekwinai,1 Juthamas Prawjaeng,2 Pattara Leelahavarong,2 Sarayuth Khuntha,3 Chatkamol Pheerapanyawaranun,4 Natthakan Chitpim,2 Varalak Srinonprasert,2,5,6 Kulkanya Chokephaibulkit4,7

1 Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
2 Siriraj Health Policy Unit, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
3 Mahidol University Health Technology Assessment Program, Mahidol University, Bangkok, Thailand
4 Siriraj Institute of Clinical Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
5 Division of Geriatric Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
6 Siriraj Research Data Management Unit, Department of Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
7 Division of Pediatric Infectious Diseases, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

Abstract

Background: The data on the immunogenicity and efficacy of heterologous primary series COVID-19 vaccination are still limited.
Objective: To investigate the immunogenicity and vaccine efficacy/effectiveness compared between heterologous and homologous primary series COVID-19 vaccination.
Methods: We conducted a multi-source search for randomized controlled trials, prospective cohort, and case-control studies that investigated the immunogenicity or vaccine efficacy/effectiveness (VE) of heterologous primary series vaccination. Six online databases were searched from inception to June 2022. The primary outcome was the levels of binding antibodies and neutralizing antibodies (NAbs), and the secondary outcomes were VE against COVID-19 infection, hospitalization, and death.
Results: Among the 28 included studies, 21 and 7 were included to investigate immunogenicity and VE outcome, respectively. Heterologous CoronaVac (CV)/ChAdOx1 (ChAd) induced higher anti-RBD IgG and NAbs against wild type and delta variants compared to homologous CV or ChAd. However, risk of documented infection of CV/ChAd was similar to homologous CV, but higher than homologous ChAd (odds ratio: 2.56, 95% CI: 1.02-6.37). Heterologous ChAd/BNT162b2 (BNT) elicited a higher anti-spike level than homologous ChAd or BNT, and induced a higher NAbs level against delta variants compared to homologous ChAd. The VE of ChAd/BNT and homologous ChAd or BNT against hospitalization were similar.
Conclusions: Heterologous CV/ChAd induced higher binding and neutralizing antibody levels than homologous CV or ChAd; and, ChAd/BNT induced higher binding and neutralizing antibody levels than homologous ChAd. However, CV/ChAd demonstrated increased risk of infection compared to homologous ChAd. Therefore, immunogenicity findings and real-world vaccine efficacy/effectiveness should be integrated in clinical practice.
Key words: Binding antibody, neutralizing antibody, vaccine efficacy/effectiveness, heterologous primary series, homologous primary series, COVID-19 vaccination, systematic review and meta-analysis