Publication: A systems approach to elucidate personalized mechanistic complexities of antibody-Fc receptor activation post-vaccination
Issued Date
2021-09-21
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ISSN
26663791
Other identifier(s)
2-s2.0-85114339770
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Mahidol University
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SCOPUS
Bibliographic Citation
Cell Reports Medicine. Vol.2, No.9 (2021)
Suggested Citation
Melissa M. Lemke, Milla R. McLean, Christina Y. Lee, Ester Lopez, Emily R. Bozich, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayaphan, Sven Kratochvil, Bruce D. Wines, P. Mark Hogarth, Stephen J. Kent, Amy W. Chung, Kelly B. Arnold A systems approach to elucidate personalized mechanistic complexities of antibody-Fc receptor activation post-vaccination. Cell Reports Medicine. Vol.2, No.9 (2021). doi:10.1016/j.xcrm.2021.100386 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/76023
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Title
A systems approach to elucidate personalized mechanistic complexities of antibody-Fc receptor activation post-vaccination
Other Contributor(s)
Faculty of Tropical Medicine, Mahidol University
University of Melbourne
University of Michigan, Ann Arbor
Massachusetts Institute of Technology
Armed Forces Research Institute of Medical Sciences, Thailand
Thailand Ministry of Public Health
Faculty of Medicine, Nursing and Health Sciences
Burnet Institute
University of Melbourne
University of Michigan, Ann Arbor
Massachusetts Institute of Technology
Armed Forces Research Institute of Medical Sciences, Thailand
Thailand Ministry of Public Health
Faculty of Medicine, Nursing and Health Sciences
Burnet Institute
Abstract
Immunoglobulin 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.