Human indels as predictors of antibody responses to COVID-19 vaccines
Vaccine efficacy varies significantly among adults. This variability underlies the limitation of a one-size-fits-all vaccination strategy and the need for more personalized approaches. We investigated factors influencing inter-individual variability in antibody responses to COVID-19 mRNA vaccine among adults. Neutralizing antibody (nAb) levels after the first vaccine dose were associated with infection outcomes within 1 year after vaccination, suggesting their potential as a correlate of protection. Age, sex, and Chinese ethnicity were associated with nAb and anti-spike protein antibody levels. Two indels located at chr1:31433042 and chr15:76311269 showed significant association with antibody responses. Leveraging these host factors, we developed a Random Forest model that predicted vaccine-induced antibody responses with 72.7% accuracy for mRNA vaccine and 76.9% for the Sinopharm COVID-19 inactivated virus vaccine. These findings support predictive modeling as a tool to identify individuals at risk of low vaccine responses, enabling more targeted and effective vaccination strategies.
Authors
- Jean‐Marc Chavatte (ORCID: https://orcid.org/0000-0002-0003-541X)
- Lisa F. P. Ng (ORCID: https://orcid.org/0000-0003-4071-5222)
- Zi Wei Chang (ORCID: https://orcid.org/0000-0002-7461-9098)
- Barnaby Edward Young (ORCID: https://orcid.org/0000-0003-1010-2230)
- Alvin Wen Choong Chua (ORCID: https://orcid.org/0000-0001-7894-9695)
- Yun Shan Goh (ORCID: https://orcid.org/0000-0003-2053-2859)
- Raymond Tzer Pin Lin (ORCID: https://orcid.org/0000-0001-6654-026X)
- Yee‐Sin Leo (ORCID: https://orcid.org/0000-0003-4978-5825)
- David Chien Lye (ORCID: https://orcid.org/0000-0003-0324-0205)
- Liang Hui Loo
- Siew‐Wai Fong (ORCID: https://orcid.org/0000-0002-5326-489X)
- Laurent Rénia (ORCID: https://orcid.org/0000-0003-0349-1557)
- Hsiuyi V. Chen (ORCID: https://orcid.org/0000-0002-5216-6710)
- Chiea Chuen Khor
- Matthew Zirui Tay (ORCID: https://orcid.org/0000-0002-1763-913X)
- Angéline Rouers (ORCID: https://orcid.org/0000-0002-8437-3204)
Institutions
- Agency for Science, Technology and Research (SG)
- National University of Singapore (SG)
- Nanyang Technological University (SG)
- Tan Tock Seng Hospital (SG)
- National University Health System (SG)
- National Centre for Infectious Diseases (SG)
- Genome Institute of Singapore (SG)
Publication Details
- Journal
- iScience
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1016/j.isci.2025.113475
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00