Title
Analysis of recombinant mycobacteria as T helper type 1 vaccines in an allergy challenge model
Author
TNO Preventie en Gezondheid
Janssen, R.
Kruisselbrink, A.
Hoogteijling, L.
Lamb, J.R.
Young, D.B.
Thole, J.E.R.
Publication year
2001
Abstract
The potential for development of mycobacteria as T helper type 1 (Th1) vaccines capable of induction of Th1 responses to recombinant antigens was explored in a model system based on an immunodominant peptide from house dust mite. Different recombinant mycobacterial preparations were compared for their ability to induce a Th1 response to the peptide. It was found that mycobacterial viability was not a prerequisite for Th1 immunogenicity. A dominant interferon-γ (IFN-γ) response to peptide was observed in splenocytes from C57BL/6J mice immunized with live or heat-killed preparations of recombinant Mycobacterium vaccae or with live attenuated bacillus Calmette-Guèrin (BCG) vaccine expressing the antigen. Interleukin-5 (IL-5), a marker of a Th2 response, was detected only in mice receiving live M. vaccae. A similar pattern was observed in BALB/b mice, although the magnitude of the IFN-γ response was much lower. Control and immunized mice were subsequently exposed to allergen using a Th2-inducing challenge protocol. A significant shift from a Th2 to a Th1 response was observed in immunized mice, as judged by cytokine expression by splenocytes and by subclass of circulating antibody. The effect was seen in three inbred mouse strains differing in their innate bias towards Th1 or Th2 responses. It was dependent on the presence of specific antigen in the mycobacterial preparation and, under the immunization conditions tested, was more pronounced with dead M. vaccae than with live BCG as carrier vaccine. The results demonstrate the potency of killed mycobacteria as Th1 adjuvants and suggest a potential application for recombinant mycobacteria in antigen-specific immune modulation. Chemicals/CAS: Adjuvants, Immunologic; Allergens; Antigens, Dermatophagoides; Bacterial Vaccines; Glycoproteins; Immunoglobulin G; Interferon Type II, 82115-62-6; Vaccines, Synthetic
Subject
antibody
BCG vaccine
epitope
gamma interferon
interleukin 5
live vaccine
recombinant antigen
recombinant vaccine
animal cell
animal experiment
controlled study
immune response
immunization
immunogenicity
immunomodulation
mouse
nonhuman
spleen cell
Th1 cell
Th2 cell
Adjuvants, Immunologic
Allergens
Animals
Antigens, Dermatophagoides
Bacterial Vaccines
Female
Glycoproteins
Immunoglobulin G
Interferon Type II
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mites
Mycobacterium
Mycobacterium bovis
Species Specificity
Spleen
Th1 Cells
Th2 Cells
Vaccines, Synthetic
To reference this document use:
http://resolver.tudelft.nl/uuid:b4502955-24b4-4ac4-aba9-039227bf3057
DOI
https://doi.org/10.1046/j.1365-2567.2001.01207.x
TNO identifier
280365
ISSN
0019-2805
Source
Immunology, 102 (102), 441-449
Document type
article