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

John D. Hart (), Eddy Fadlyana, Nadia Mazarakis, Nina Dwi Putri, Emma Watts, Kerryn A. Moore, Eleanor F. G. Neal, Djatnika Setiabudi, Muhammad Gilang Dwi Putra, Cattram Nguyen, Aqila Sakina Zhafira, Pratama Wicaksana, Robert Sinto, Dwi Oktavia, Rini Fajarani, Agnes Rengga Indrati, Chrysanti Murad, Yovita Hartantri, Hendarsyah Suryadinata, Yulia Sofiatin, Kusnandi Rusmil, Hindra I. Satari, Sri Rezeki. Hadinegoro, Cissy B. Kartasasmita, Julitasari Sundoro, Paul V. Licciardi, Claire von Mollendorf and Edward K. Mulholland
Additional contact information
John D. Hart: Murdoch Children’s Research Institute
Eddy Fadlyana: Universitas Padjadjaran
Nadia Mazarakis: Murdoch Children’s Research Institute
Nina Dwi Putri: The University of Melbourne
Emma Watts: Murdoch Children’s Research Institute
Kerryn A. Moore: Murdoch Children’s Research Institute
Eleanor F. G. Neal: Murdoch Children’s Research Institute
Djatnika Setiabudi: Universitas Padjadjaran
Muhammad Gilang Dwi Putra: Universitas Padjadjaran
Cattram Nguyen: Murdoch Children’s Research Institute
Aqila Sakina Zhafira: Universitas Indonesia
Pratama Wicaksana: Universitas Indonesia
Robert Sinto: Dr Cipto Mangunkusumo General Hospital
Dwi Oktavia: Jakarta Provincial Health Office
Rini Fajarani: Universitas Indonesia
Agnes Rengga Indrati: Universitas Padjadjaran
Chrysanti Murad: Universitas Padjadjaran
Yovita Hartantri: Universitas Padjadjaran
Hendarsyah Suryadinata: Universitas Padjadjaran
Yulia Sofiatin: Universitas Padjadjaran
Kusnandi Rusmil: Universitas Padjadjaran
Hindra I. Satari: Universitas Indonesia
Sri Rezeki. Hadinegoro: Universitas Indonesia
Cissy B. Kartasasmita: Universitas Padjadjaran
Julitasari Sundoro: Ministry of Health of Indonesia
Paul V. Licciardi: Murdoch Children’s Research Institute
Claire von Mollendorf: Murdoch Children’s Research Institute
Edward K. Mulholland: Murdoch Children’s Research Institute

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-63598-6

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