A Test-Negative Design for Immune Correlates Approximates a Traditional Exposure-Proximal Design but Requires Far Fewer Blood Samples
Traditional vaccine clinical trials sample blood from all participants. In contrast, the test-negative immune correlates (TNIC) design only samples blood from participants who develop symptoms. We compared traditional to test-negative immune correlates methods in the mRNA-1273 severe acute respiratory syndrome coronavirus 2 vaccine efficacy clinical trial. Using a neutralizing antibody assay, hazard ratios were 0.48 (95% confidence interval [CI], .29-.73) and 0.55 (95% CI, .28-1.06) for traditional and test-negative methods, respectively. Analogous ratios for binding antibody assay were 0.69 (95% CI, .52-.94) and 0.78 (95% CI, .50-1.20). The results support use of the logistically simpler TNIC design.
Authors
- Leah Andrews (ORCID: https://orcid.org/0000-0002-3418-9468)
- Haiyu Zhou (ORCID: https://orcid.org/0000-0002-3328-6792)
- Bob C. Lin (ORCID: https://orcid.org/0000-0002-1373-1406)
- Avika Dixit (ORCID: https://orcid.org/0000-0002-8381-3298)
- Richard A. Koup (ORCID: https://orcid.org/0000-0002-3090-7282)
- Hana M. El Sahly (ORCID: https://orcid.org/0000-0003-0489-0074)
- Eric Chun‐Pu Chu (ORCID: https://orcid.org/0000-0002-0893-556X)
- Jonathan Fintzi (ORCID: https://orcid.org/0000-0002-6361-702X)
- Frances Priddy (ORCID: https://orcid.org/0000-0002-2533-3982)
- Jon Toma
- Holly Janes (ORCID: https://orcid.org/0000-0002-3237-984X)
- Dean A. Follmann (ORCID: https://orcid.org/0000-0003-4073-0393)
- Leonid Serebryannyy (ORCID: https://orcid.org/0000-0003-0213-1779)
- L Weiping Deng
- Peter B. Gilbert (ORCID: https://orcid.org/0000-0002-2662-9427)
- Lindsey Robert Baden (ORCID: https://orcid.org/0009-0004-1752-1926)
- Lauren Dang (ORCID: https://orcid.org/0009-0003-2865-1155)
- Robin Carroll
Institutions
- Brigham and Women's Hospital (US)
- National Institutes of Health (US)
- Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA)
- Baylor College of Medicine (US)
- University of Washington (US)
- Biomedical Advanced Research and Development Authority (US)
- Fred Hutch Cancer Center (US)
- Moderna Therapeutics (United States) (US)
- IGM Biosciences (United States) (US)
- Frederick National Laboratory for Cancer Research (US)
- National Institute of Allergy and Infectious Diseases (US)
Publication Details
- Journal
- The Journal of Infectious Diseases
- Published
- 2025-11-13
- DOI
- https://doi.org/10.1093/infdis/jiaf572
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00