Two-Dose Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Effectiveness With Mixed Schedules and Extended Dosing Intervals: Test-Negative Design Studies From British Columbia and Quebec, Canada
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Abstract
Background: The Canadian coronavirus disease 2019 (COVID-19) immunization strategy deferred second doses and allowed mixed schedules. We compared 2-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in 2 of Canada’s larger provinces. Methods: Two-dose VE against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or hospitalization among adults ≥18 years, including due to Alpha, Gamma, and Delta variants of concern (VOCs), was assessed ≥14 days postvaccination by test-negative design studies separately conducted in British Columbia and Quebec, Canada, between 30 May and 27 November (epi-weeks 22–47) 2021. Results: In both provinces, all homologous or heterologous mRNA and/or ChAdOx1 2-dose schedules were associated with ≥90% reduction in SARS-CoV-2 hospitalization risk for ≥7 months. With slight decline from a peak of >90%, VE against infection was ≥80% for ≥6 months following homologous mRNA vaccination, lower by ∼10% when both doses were ChAdOx1 but comparably high following heterologous ChAdOx1 + mRNA receipt. Findings were similar by age group, sex, and VOC. VE was significantly higher with longer 7–8-week versus manufacturer-specified 3–4-week intervals between mRNA doses. Conclusions: Two doses of any mRNA and/or ChAdOx1 combination gave substantial and sustained protection against SARS-CoV-2 hospitalization, spanning Delta-dominant circulation. ChAdOx1 VE against infection was improved by heterologous mRNA series completion. A 7–8-week interval between first and second doses improved mRNA VE and may be the optimal schedule outside periods of intense epidemic surge. Findings support interchangeability and extended intervals between SARS-CoV-2 vaccine doses, with potential global implications for low-coverage areas and, going forward, for children.
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A growing number of studies suggest that an extended dosing interval amplifies both the humoral immune response and perhaps the cellular response, and is an effective global strategy given discrepancies between regions with high and low vaccination coverage.
“Nonetheless, a growing number of studies suggest that an extended dosing interval amplifies both the humoral immune response30 and perhaps the cellular response,31 and is an effective global strategy given the discrepancies between regions with high and low vaccination coverage.32”
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- Authors
- Skowronski, D. M., Febriani, Y., Ouakki, M., Setayeshgar, S., El Adam, S., Zou, M., Talbot, D., Prystajecky, N., Tyson, J. R., Gilca, R., Brousseau, N., Deceuninck, G., Galanis, E., Fjell, C. D., Sbihi, H., Fortin, E., Barkati, S., Sauvageau, C., Naus, M., Patrick, D. M., Henry, B., Hoang, L. M. N., De Wals, P., Garenc, C., Carignan, A., Drolet, M., Jassem, A. N., Sadarangani, M., Brisson, M., Krajden, M., & De Serres, G.
- Affiliations
- University of British Columbia (CA)
- Centre hospitalier universitaire de Québec (CA)
- Institut National de Sante Publique du Québec, Biological and Occupational Risks , Quebec City, Quebec , Canada
- BC Centre for Disease Control (CA)
- BC Centre for Disease Control, Communicable Diseases and Immunization Services , Vancouver, British Columbia , Canada
- BC Centre for Disease Control, Public Health Laboratory , Vancouver, British Columbia , Canada
- McGill University Health Centre (CA)
- Ministry of Health (CA)
- Centre Hospitalier Universitaire (CHU) de Québec-Université Laval Research Center , Quebec City, Quebec , Canada
- Université de Sherbrooke (CA)
- Corresponding author
- Skowronski, Danuta M
- ORCID
- Skowronski, Danuta M
- Febriani, Yossi
- Setayeshgar, Solmaz
- Talbot, Denis
- Prystajecky, Natalie
- Tyson, John R
- Gilca, Rodica
- Brousseau, Nicholas
- Deceuninck, Geneviève
- Galanis, Eleni
- Sbihi, Hind
- Barkati, Sapha
- Sauvageau, Chantal
- Naus, Monika
- Hoang, Linda M N
- Carignan, Alex
- Drolet, Mélanie
- Jassem, Agatha N
- Sadarangani, Manish
- Brisson, Marc
- Krajden, Mel
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2022-04-19
- Volume
- 75
- Issue
- 11
- Pages
- 1980-1992
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- PMC
- PMC9047203
- OpenAlex
- W4226124668
- Cited by
- 155
- References
- 22
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 19 · 2023: 40 · 2022: 69 · 2021: 9
- FWCI
- 17.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinical Infectious Diseases (publishedVersion, cc-by-nc-nd)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Children's Hospital Foundation
- BC Children's Hospital
- Canadian Child Health Clinician Scientist Program
- Michael Smith Health Research BC
- British Columbia Centre for Disease Control
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Social Sciences › Health › Vaccine Coverage and Hesitancy
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Keywords
- COVID-19 vaccine effectiveness, SARS-CoV-2, two-dose vaccine schedule, extended dosing interval, heterologous vaccination, mRNA vaccines, ChAdOx1 nCoV-19 vaccine, SARS-CoV-2 variants of concern, Delta variant, test-negative design, vaccine interchangeability, British Columbia, Quebec
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, Vaccine Efficacy, Adult, British Columbia, Child, Humans, Quebec, RNA, Messenger
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