Using data from macaques to predict gamma interferon responses after mycobacterium bovis BCG vaccination in humans: a proof-of-concept study of immunostimulation/immunodynamic modeling methods
Author(s)
Type
Journal Article
Abstract
Macaques play a central role in the development of human tuberculosis (TB) vaccines. Immune and challenge responses differ across macaque and human subpopulations. We used novel immunostimulation/immunodynamic modeling methods in a proof-of-concept study to determine which macaque subpopulations best predicted immune responses in different human subpopulations. Data on gamma interferon (IFN-γ)-secreting CD4+ T cells over time after recent Mycobacterium bovis BCG vaccination were available for 55 humans and 81 macaques. Human population covariates were baseline BCG vaccination status, time since BCG vaccination, gender, and the monocyte/lymphocyte cell count ratio. The macaque population covariate was the colony of origin. A two-compartment mathematical model describing the dynamics of the IFN-γ T cell response after BCG vaccination was calibrated to these data using nonlinear mixed-effects methods. The model was calibrated to macaque and human data separately. The association between subpopulations and the BCG immune response in each species was assessed. The macaque subpopulations that best predicted immune responses in different human subpopulations were identified using Bayesian information criteria. We found that the macaque colony and the human baseline BCG status were significantly (P < 0.05) associated with the BCG-induced immune response. For humans who were BCG naïve at baseline, Indonesian cynomolgus macaques and Indian rhesus macaques best predicted the immune response. For humans who had already been BCG vaccinated at baseline, Mauritian cynomolgus macaques best predicted the immune response. This work suggests that the immune responses of different human populations may be best modeled by different macaque colonies, and it demonstrates the potential utility of immunostimulation/immunodynamic modeling to accelerate TB vaccine development.
Date Issued
2017-01-11
Date Acceptance
2017-01-04
Citation
Clinical and Vaccine Immunology, 2017, 24 (3)
ISSN
1556-679X
Publisher
American Society for Microbiology
Journal / Book Title
Clinical and Vaccine Immunology
Volume
24
Issue
3
Copyright Statement
© 2017 Rhodes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/)
Sponsor
National Institute for Health Research
National Institute for Health Research
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000395796300002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
HPRU-2012-10047
HPRU-2012-10047
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Infectious Diseases
Microbiology
nonhuman primates
T-cell immunity
bacillus Calmette-Guerin
interferons
mathematical modeling
tuberculosis
tuberculosis vaccines
CALMETTE-GUERIN VACCINATION
TUBERCULOSIS VACCINE
CYNOMOLGUS MONKEYS
AEROSOL CHALLENGE
IMMUNE-RESPONSES
PRIMATE MODELS
MEMORY
PROTECTION
IMMUNOGENICITY
INITIATION
Publication Status
Published
Article Number
UNSP e00525