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Learning from the omicron BA.4/5 dominance: Strategies for future vaccination preparedness
Jialiang Jiang1, Kwok Fai Lam2, Eric Ho Yin Lau3
1Department of Statistics and Actuarial Science, School of Computing and Data Science, The University of Hong Kong, Hong Kong Special Administrative Region of China.
Vaccine
|December 4, 2025
Summary
Heterologous boosting with mRNA vaccines after inactivated vaccines and using bivalent vaccines significantly improve COVID-19 protection. Vaccination before infection offers superior immunity compared to infection-first strategies, guiding future pandemic responses.
Area of Science:
- Immunology
- Epidemiology
- Public Health
Background:
- Waning immunity (>6 months) necessitates understanding optimal COVID-19 booster strategies against Omicron BA.4/5.
- Investigating the impact of vaccination-infection sequence on immune protection is crucial for public health policy.
Purpose of the Study:
- To evaluate the effectiveness of different COVID-19 booster strategies against Omicron BA.4/5.
- To determine the influence of vaccination-infection sequence on subsequent immunity.
Main Methods:
- Territory-wide observational study of 1,737,475 adults in Hong Kong (Nov 2022-Jan 2023).
- Andersen-Gill model used to assess infection risks across various vaccination and infection history cohorts.
- Comparison of homologous vs. heterologous boosting, bivalent vs. standard vaccines, and vaccination-first vs. infection-first approaches.
Main Results:
- Platform-switching heterologous boosting (inactivated to mRNA) reduced infection risk by 9-21% compared to homologous strategies.
- Bivalent Omicron BA.4/BA.5 BNT162b2 vaccines offered 30-58% lower hazard than standard BNT162b2 vaccines.
- Vaccination-first strategies provided superior protection; infection-first CoronaVac recipients had 97-141% higher subsequent infection risk.
Conclusions:
- Platform-switching heterologous boosting and bivalent vaccines enhance protection against COVID-19.
- Vaccination-first approaches are consistently more effective than infection-first strategies.
- Findings support proactive vaccination policies and inform rapid response strategies for future pandemics.
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