Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Previously we have shown that intradermal (i.d.) immunization with a recombinant adenovirus expressing antigen 85A (Ad85A) induced a strong splenic CD8T cell response in BALB/c mice but a weak lung immune response and did not protect mice against challenge with Mycobacterium tuberculosis (Mtb). After moving to a new animal house, the same i.d. immunization induced a strong lung immune response and the mice were protected against Mtb challenge. Increased numbers of antigen 85A-specific CD8 cells were present in lung tissue but were not recoverable by bronchoalveolar lavage (BAL). Mycobacterial growth was inhibited 21 days after Mtb challenge. In contrast, the effects of intranasal (i.n.) immunization did not change between the animal houses; 85A-specific T cells were recovered by BAL and were able to inhibit Mtb growth early after challenge. The effect of alterations to the environment was investigated by administering BCG or Mycobacterium abscessus in the drinking water, which induced protection against Mtb challenge, while Mycobacterium smegmatis did not. However, when Ad85A was given i.d. at the same time as BCG or M. abscessus, but not M. smegmatis, the protection induced by Ad85A was abolished. Treatment of mice with a CD25 antibody during the challenge period, abolished the suppressive effect of oral mycobacterial administration, suggesting that regulatory T cells (T regs) were involved. These results showed that exposure to environmental microorganisms can alter the protective immune response to a parenterally administered subunit vaccine, a result with important implications for the use of such vaccines in humans.

Original publication

DOI

10.1016/j.vaccine.2012.12.024

Type

Journal article

Journal

Vaccine

Publication Date

04/02/2013

Volume

31

Pages

1086 - 1093

Keywords

Acyltransferases, Administration, Intranasal, Animals, Antigens, Bacterial, Bronchoalveolar Lavage Fluid, CD8-Positive T-Lymphocytes, Disease Models, Animal, Environmental Microbiology, Female, Injections, Intradermal, Lung, Mice, Mice, Inbred BALB C, Mycobacterium tuberculosis, Tuberculosis, Tuberculosis Vaccines