A systems approach to elucidate personalized mechanistic complexities of antibody-Fc receptor activation post-vaccination

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

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6 Citations (Scopus)


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.

Original languageEnglish
Article number100386
Number of pages20
JournalCell Reports Medicine
Issue number9
Publication statusPublished - 21 Sept 2021


  • ADCC
  • Fc receptor
  • HIV
  • IgG
  • ODE model
  • precision medicine
  • RV144
  • sensitivity analysis
  • systems serology
  • vaccine

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