Journal article

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

CELL REPORTS MEDICINE | ELSEVIER | Published : 2021

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 ..

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Grants

Awarded by Australia National Health & Medical Research Center (NHMRC)


Awarded by American Foundation for AIDS Research (amfAR) Mathilde Krim Fellowship


Funding Acknowledgements

,This work was supported by the Australia National Health & Medical Research Center (NHMRC) (APP1125164 to A.W.C.) and the American Foundation for AIDS Research (amfAR) Mathilde Krim Fellowship (109499-61-RKVA to A.W.C), and by start-up funds from the University of Michigan to K.B.A.. S.J.K., and A.W.C. were supported by NHMRC fellowships. The data necessary to calculate allotype conversion was generously shared by Robin J. Shattock and Paul F. McKay (Imperial College, London). The authors would like to thank the participants in the RV144 trial, as well as Paul Wolberg and Denise Kirschner (University of Michigan) for assistance in implementing the globalsensitivity analysis, and Katy Norman and Katarina DiLillo (University of Michigan) for manuscript review.