Melissa M. LemkeMilla R. McLeanChristina Y. LeeEster LopezEmily R. BozichSupachai Rerks-NgarmPunnee PitisuttithumSorachai NitayaphanSven KratochvilBruce D. WinesP. Mark HogarthStephen J. KentAmy W. ChungKelly B. ArnoldFaculty of Tropical Medicine, Mahidol UniversityUniversity of MelbourneUniversity of Michigan, Ann ArborMassachusetts Institute of TechnologyArmed Forces Research Institute of Medical Sciences, ThailandThailand Ministry of Public HealthFaculty of Medicine, Nursing and Health SciencesBurnet Institute2022-08-042022-08-042021-09-21Cell Reports Medicine. Vol.2, No.9 (2021)266637912-s2.0-85114339770https://repository.li.mahidol.ac.th/handle/123456789/76023Immunoglobulin G (IgG) antibodies that activate Fc-mediated immune functions have been correlated with vaccine efficacy, but it is difficult to unravel the relative roles of multiple IgG and Fc receptor (FcR) features that have the capacity to influence IgG-FcR complex formation but vary on a personalized basis. Here, we develop an ordinary differential-equation model to determine how personalized variability in IgG subclass concentrations and binding affinities influence IgG-FcγRIIIa complex formation and validate it with samples from the HIV RV144 vaccine trial. The model identifies individuals who are sensitive, insensitive, or negatively affected by increases in HIV-specific IgG1, which is validated with the addition of HIV-specific IgG1 monoclonal antibodies to vaccine samples. IgG1 affinity to FcγRIIIa is also prioritized as the most influential parameter for dictating activation broadly across a population. Overall, this work presents a quantitative tool for evaluating personalized differences underlying FcR activation, which is relevant to ongoing efforts to improve vaccine efficacy.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyMedicineArticleSCOPUS10.1016/j.xcrm.2021.100386