Nature communicationsSep 29, 2025

Immune response to smaller and full COVID-19 vaccine booster doses in healthy adults in Indonesia over 24 months

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jan 7, 2026

Abstract

Of 1,289 trial participants, 962 (75%) completed follow-up to 24 months after receiving booster doses.

Among participants initially vaccinated with CoronaVac, immune responses were lower with fractional doses of Pfizer compared to standard doses at 28 days.
Differences in immune responses between fractional and standard doses diminished by 12 and 24 months.
Participants primed with AstraZeneca demonstrated lower initial immune responses compared to those primed with CoronaVac after receiving Pfizer and AstraZeneca boosters.
Breakthrough infections were reported in over 40% of participants between six and 12 months, and in over 35% between 12 and 24 months.
Both fractional and standard doses of AstraZeneca and Pfizer boosted immune responses among participants primed with either CoronaVac or AstraZeneca.

Simplified

Although many high-income countries have regular COVID-19 vaccine booster schedules, there are limited data on the protective effects of some heterologous booster combinations. This observational follow-up study of a double blind randomised controlled parallel group trial evaluates long-term immunogenicity, safety and breakthrough infections to 24 months after booster doses (fractional or standard Pfizer BNT162b2, fractional or standard AstraZeneca ChAdOx1, and standard dose CoronaVac) following CoronaVac and AstraZeneca primary series in healthy adults in Indonesia. Of 1,289 trial participants, 962 (75%) complete follow-up to 24 months. Among CoronaVac-primed participants, responses are lower for fractional than standard dose Pfizer at 28 days (binding IgG geometric mean ratio: 0.75, 95% CI: 0.63-0.90), but differences diminish by 12 and 24 months. AstraZeneca-primed participants have lower initial responses than CoronaVac-primed participants following Pfizer and AstraZeneca boosters. Breakthrough infections occurred in >40% of participants between six and 12 months, and in >35% between 12 and 24 months. Fractional and standard doses of AstraZeneca and Pfizer among CoronaVac-primed or AstraZeneca-primed participants, boost immune responses to 24 months. However, fractional doses elicit lower initial responses than standard doses. These findings provide important information for booster strategies, especially in populations primed with inactivated vaccines. Funding: Coalition for Epidemic Preparedness Innovations (CEPI). Trial registration: ina-registry.org , INA-GO0HLGB.

Key numbers

3740 BAU/ml

Initial Immune Response ()

of binding antibodies in participants boosted with Pfizer fractional doses at 28 days.

>40%

Rate

Percentage of participants experiencing breakthrough infections between 6 and 12 months.

4969 BAU/ml

Antibody Response Comparison

of binding antibodies in participants boosted with Pfizer standard doses at 28 days.

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Funding

Competing interests

Competing interests: C.B.K., S.R.H., and J.S. are members of the Indonesian Technical Advisory Group on Immunisation. All other authors declare no competing interests.

PubMed

Immune response to smaller and full COVID-19 vaccine booster doses in healthy adults in Indonesia over 24 months

Abstract

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