Publications & Reports

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

Lemke MM, McLean MR, Lee CY, Lopez E, Bozich ER, Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kratochvil S, **Wines BD**, Hogarth PM, Kent SJ, Chung AW, Arnold KB
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.


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-FcgammaRIIIa 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 FcgammaRIIIa 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.

Link to publisher’s web site


  • Journal: Cell Reports. Medicine
  • Published: 21/09/2021
  • Volume: 2
  • Issue: 9
  • Pagination: 100386



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