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

Cell Rep Med. 2021 Sep 1;2(9):100386. doi: 10.1016/j.xcrm.2021.100386. eCollection 2021 Sep 21.


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.

Keywords: ADCC; Fc receptor; HIV; IgG; ODE model; RV144; precision medicine; sensitivity analysis; systems serology; vaccine.

Publication types

  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't

MeSH terms

  • HIV Antibodies / immunology*
  • Humans
  • Immunoglobulin G / metabolism
  • Models, Biological
  • Precision Medicine*
  • Receptors, Fc / metabolism*
  • Receptors, IgG / metabolism
  • Reproducibility of Results
  • Systems Analysis*
  • Vaccination*
  • env Gene Products, Human Immunodeficiency Virus / metabolism


  • FCGR3A protein, human
  • HIV Antibodies
  • Immunoglobulin G
  • Receptors, Fc
  • Receptors, IgG
  • env Gene Products, Human Immunodeficiency Virus

Associated data

  • figshare/10.6084/m9.figshare.14810397