Immunogenicity of fractional and standard dose COVID-19 vaccine boosters among healthy adults in Indonesia: twenty four month follow-up from a randomised controlled trial

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.

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Publication Details

Journal
Nature Communications
Published
2025-09-29
DOI
https://doi.org/10.1038/s41467-025-63598-6
Citations
3
Primary Topic
SARS-CoV-2 and COVID-19 Research
Type
article
Field-Weighted Citation Impact
4.19
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article

Immunogenicity of fractional and standard dose COVID-19 vaccine boosters among healthy adults in Indonesia: twenty four month follow-up from a randomised controlled trial

Muhammad Gilang Dwi Putra, Pratama Wicaksana, Paul V. Licciardi, Kim Mulholland et al.
3 citations
Nature Communications
SARS-CoV-2 and COVID-19 Research
4.19
article

Immunogenicity of fractional and standard dose COVID-19 vaccine boosters among healthy adults in Indonesia: twenty four month follow-up from a randomised controlled trial

Muhammad Gilang Dwi Putra, Pratama Wicaksana, Paul V. Licciardi, Kim Mulholland, Eddy Fadlyana, Julitasari Sundoro, Yovita Hartantri, Dwi Oktavia, Emma Watts, Djatnika Setiabudi, Cissy B. Kartasasmita, Cattram Nguyen, Hendarsyah Suryadinata, Nadia Mazarakis, John Hart, Hindra Irawan Satari, Kerryn A. Moore, Kusnandi Rusmil, Rini Fajarani, Claire von Mollendorf, Chrysanti Murad, Yulia Sofiatin, Agnes Rengga Indrati, Aqila Sakina Zhafira, Nina Dwi Putri, Eleanor Neal, Robert Sinto, Sri Rezeki Hadinegoro
article en
3 citations

Abstract

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.

Nature CommunicationsVol. 16(1)
The University of Melbourne (AU), University of Indonesia (ID), London School of Hygiene & Tropical Medicine (GB), Kementerian Kesehatan Republik Indonesia (ID), Murdoch Children's Research Institute (AU), Rumah Sakit Umum Pusat Nasional Dr. Cipto Mangunkusumo (ID), Padjadjaran University (ID)
Openalex Percentile: Top 5%
SARS-CoV-2 and COVID-19 Research
4.19
DOIOpen Access PDFOpenAlex
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