Immune response and safety of heterologous ChAdOx1-nCoV-19/mRNA-1273 vaccination compared with homologous ChAdOx1-nCoV-19 or homologous mRNA-1273 vaccination

Wang-Huei Sheng; Sui-Yuan Chang; Pin-Hung Lin; Ming-Ju Hsieh; Hao-Hsiang Chang; Chien-Yu Cheng; Hung-Chih Yang; Ching-Fu Pan; Si-Man Ieong; Tai-Ling Chao; Jang-Pin Chen; Shu-Hsing Cheng; Shan-Chwen Chang

doi:10.1016/j.jfma.2022.02.020

Immune response and safety of heterologous ChAdOx1-nCoV-19/mRNA-1273 vaccination compared with homologous ChAdOx1-nCoV-19 or homologous mRNA-1273 vaccination

J Formos Med Assoc. 2022 Apr;121(4):766-777. doi: 10.1016/j.jfma.2022.02.020. Epub 2022 Mar 16.

Authors

Affiliations

¹ Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan; School of Medicine, National Taiwan University College of Medicine, Taipei City, Taiwan.
² Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei City, Taiwan.
³ Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁴ Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan; Occupational Safety and Health Office, National Taiwan University Hospital, Taipei, Taiwan.
⁵ Department of Family Medicine, National Taiwan University Hospital and College of Medicine, Taipei 10016, Taiwan.
⁶ Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan; Institute of Public Health, School of Medicine National Yang-Ming Chiao Tung University, Taiwan.
⁷ Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan; Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁸ Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
⁹ Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
¹⁰ Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan; School of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan.
¹¹ Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan; Institute of Public Health, School of Medicine National Yang-Ming Chiao Tung University, School of Public Health, Taipei Medical University, Taipei, Taiwan.
¹² Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan; School of Medicine, National Taiwan University College of Medicine, Taipei City, Taiwan. Electronic address: changsc@ntu.edu.tw.

Abstract

Background/purpose: Efficacy and safety data of heterologous prime-boost vaccination against SARS-CoV-2 remains limited.

Methods: We recruited adult volunteers for homologous or heterologous prime-boost vaccinations with adenoviral (ChAdOx1, AstraZeneca) and/or mRNA (mRNA-1273, Moderna) vaccines. Four groups of prime-boost vaccination schedules were designed: Group 1, ChAdOx1/ChAdOx1 8 weeks apart; Group 2, ChAdOx1/mRNA-1273 8 weeks apart; Group 3, ChAdOx1/mRNA-1273 4 weeks apart; and Group 4, mRNA-1273/mRNA-1273 4 weeks apart. The primary outcome was serum anti-SARS-CoV-2 IgG titers and neutralizing antibody titers against B.1.1.7 (alpha) and B.1.617.2 (delta) variants on day 28 after the second dose. Adverse events were recorded up until 84 days after the second dose.

Results: We enrolled 399 participants with a median age of 41 years and 75% were female. On day 28 after the second dose, the anti-SARS-CoV-2 IgG titers of both heterologous vaccinations (Group 2 and Group 3) were significantly higher than that of homologous ChAdOx1 vaccination (Group 1), and comparable with homologous mRNA-1273 vaccination (Group 4). The heterologous vaccination group had better neutralizing antibody responses against the alpha and delta variant as compared to the homologous ChAdOx1 group. Most of the adverse events (AEs) were mild and transient. AEs were less frequent when heterologous boosting was done at 8 weeks rather than at 4 weeks.

Conclusion: Heterologous ChAdOx1/mRNA-1273 vaccination provided higher immunogenicity than homologous ChAdOx1 vaccination and comparable immunogenicity with the homologous mRNA-1273 vaccination. Our results support the safety and efficacy of heterologous prime-boost vaccination using the ChAdOx1 and mRNA-1273 COVID-19 vaccines. (ClinicalTrials.gov number, NCT05074368).

Keywords: Adenovirus-vector vaccine; Coronavirus disease 2019 (COVID-19); Immune response; Messenger RNA vaccine; Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2).

Publication types

Clinical Study

MeSH terms

2019-nCoV Vaccine mRNA-1273
Adult
COVID-19 Vaccines / adverse effects
COVID-19* / prevention & control
ChAdOx1 nCoV-19
Female
Humans
Immunity
SARS-CoV-2*
Vaccination

Substances

COVID-19 Vaccines
ChAdOx1 nCoV-19
2019-nCoV Vaccine mRNA-1273

Supplementary concepts

SARS-CoV-2 variants

Associated data

ClinicalTrials.gov/NCT05074368