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bioRxiv · 10.1101/2025.07.18.665557

Immune Biomarkers, Profiles, and Responses: A Vaccine Ontology Perspective

He, Y.·Huffman, A.·Zheng, J.·Masci, A. M.·Lin, A. Y.·Smith, B.
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Abstract

BackgroundVaccines have the ability to induce a range of immune responses under different conditions, for example stimulating the production of neutralizing antibodies to block pathogen entry or activating cytotoxic T-cells to eliminate infected cells. Many such immune responses have not been thoroughly examined and classified. The Vaccine Ontology (VO) is a community-based ontology in the domain of vaccinology. We here describe how VO is used to represent the variety of immune responses associated with vaccines, together with associated biomarkers and profiles. ResultsThe VO differentiates vaccination and vaccine immunization. The former is a process of administering a vaccine in vivo; the latter is the outcome of vaccine induction of immune response. This distinction is critical for understanding both the procedure of vaccination and the resulting immune effects. VO also models and represents various vaccine-induced responses at multiple biological levels, including population, organism, organ/tissue, cell, and gene/protein levels. Such an approach captures the complexity of vaccine-induced immunity, from population-wide trend (for example: herd immunity) to molecular mechanisms. VO defines immune biomarkers as material entities such as neutralizing antibodies that signify humoral immune response, and IFN-gamma that is indicative of cell-mediated responses. Such biomarkers provide measurable indicators of the immune systems functional state post vaccination, enabling robust evaluation of vaccine efficacy. VO classifies immune response profile and correlated profile (or correlate) of immune protection as process profiles, a class in the Basic Formal Ontology (BFO 2.0). Immune response profiles, such as Th1 (or Th2)- biased profile, can be induced by various vaccines and vaccine adjuvants. Different types of correlated profile of immune protection are also identified, such as mechanistic and non-mechanistic correlates of immune protection. Such distinctions help us to quickly identify biomarkers and associated prediction and measurement of different kinds of vaccine protection. ConclusionThe important immune-related terms for immune biomarkers, profiles, and responses are modeled ontologically in VO together with their interrelations. The results support enhanced classification and analysis of vaccine-induced immune responses and related biomarkers and immune profiles, leading to further understanding of the vaccine immune mechanisms and enhanced vaccine research and development.

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He, Y., Huffman, A., Zheng, J., Masci, A. M., Lin, A. Y., Smith, B.. 2025-07-22. Immune Biomarkers, Profiles, and Responses: A Vaccine Ontology Perspective. https://doi.org/10.1101/2025.07.18.665557

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