Machine learning methods enable predictive modeling of antibody feature:function relationships in RV144 vaccinees

PLoS Comput Biol. 2015 Apr 13;11(4):e1004185. doi: 10.1371/journal.pcbi.1004185. eCollection 2015 Apr.

Abstract

The adaptive immune response to vaccination or infection can lead to the production of specific antibodies to neutralize the pathogen or recruit innate immune effector cells for help. The non-neutralizing role of antibodies in stimulating effector cell responses may have been a key mechanism of the protection observed in the RV144 HIV vaccine trial. In an extensive investigation of a rich set of data collected from RV144 vaccine recipients, we here employ machine learning methods to identify and model associations between antibody features (IgG subclass and antigen specificity) and effector function activities (antibody dependent cellular phagocytosis, cellular cytotoxicity, and cytokine release). We demonstrate via cross-validation that classification and regression approaches can effectively use the antibody features to robustly predict qualitative and quantitative functional outcomes. This integration of antibody feature and function data within a machine learning framework provides a new, objective approach to discovering and assessing multivariate immune correlates.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AIDS Vaccines / immunology*
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Computational Biology
  • Cytokines / blood
  • Cytokines / immunology
  • HIV Antibodies / blood
  • HIV Antibodies / immunology*
  • HIV Antigens / blood
  • HIV Antigens / immunology
  • HIV Infections / immunology*
  • HIV-1 / immunology
  • Humans
  • Machine Learning*
  • Models, Immunological*

Substances

  • AIDS Vaccines
  • Cytokines
  • HIV Antibodies
  • HIV Antigens