title: Machine learning methods enable predictive modeling of antibody feature:function relationships in RV144 vaccinees.
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.
authors: Department of Computer Science, Dartmouth College, Hanover, New Hampshire, United States of America.
authors: Ickwon
authors: I
authors: Choi
authors: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston, Massachusetts, United States of America.
authors: Amy W
authors: AW
authors: Chung
authors: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston, Massachusetts, United States of America.
authors: Todd J
authors: TJ
authors: Suscovich
authors: Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand.
authors: Supachai
authors: S
authors: Rerks-Ngarm
authors: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors: Punnee
authors: P
authors: Pitisuttithum
authors: Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors: Sorachai
authors: S
authors: Nitayaphan
authors: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors: Jaranit
authors: J
authors: Kaewkungwal
authors: Department of Retrovirology, U.S. Army Medical Component, AFRIMS, Bangkok, Thailand.
authors: Robert J
authors: RJ
authors: O'Connell
authors: Global Solutions for Infectious Diseases (GSID), South San Francisco, California, United States of America.
authors: Donald
authors: D
authors: Francis
authors: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America; Henry Jackson Foundation HIV Program, US Military HIV Research Program, Bethesda, Maryland, United States of America.
authors: Merlin L
authors: ML
authors: Robb
authors: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors: Nelson L
authors: NL
authors: Michael
authors: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors: Jerome H
authors: JH
authors: Kim
authors: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston, Massachusetts, United States of America.
authors: Galit
authors: G
authors: Alter
authors: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, United States of America.
authors: Margaret E
authors: ME
authors: Ackerman
authors: Department of Computer Science, Dartmouth College, Hanover, New Hampshire, United States of America.
authors: Chris
authors: C
authors: Bailey-Kellogg
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D019295:Computational Biology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D015488:HIV Antigens / Q000097:blood / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D000069550:Machine Learning; D018448:Models, Immunological
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D015483:HIV Antibodies; D015488:HIV Antigens