We have increasing evidence that the protective effect of BCG varies widely between strains of M. tuberculosis [mostly of the Beijing family] isolated from patients in the USA, and those collected in the Western Cape of South Africa, the site of current TB vaccine trials. We have shown that BCG is only transiently protective against the US Beijing strains, but highly protective against two Western Cape strains in guinea pigs. The purpose of this R21 application therefore is to test [a] the efficacy of BCG against two larger panels representative of the two groups of isolates to see if our preliminary data is a collective phenomenon, and [b] to test the hypothesis that strains that have the capacity to resist the protective effects of BCG are able to do so because they potently induce regulatory T cells that inhibit this immunity, a hypothesis based on considerable new evidence from our laboratory. Not only do these studies have significant public health implications, notably for new vaccine trials, but if the Western Cape strains are as sensitive to BCG as our preliminary data suggests, they provide an explanation for the failure of the recent MVA85A trial. These studies will be conducted in our state of the art level-III facilities at CSU using conventional techniques at whic we are adept.

Public Health Relevance

We have increasing evidence that a pool of [mostly] Beijing strains of M. tuberculosis isolated within the USA are highly resistant to the effects of BCG vaccination in small animal models, whereas isolates from the Western Cape of South Africa are strongly inhibited by the vaccine. This proposed study will test the hypothesis that the underlying mechanism for these events reflects the preferential ability of the US strains to potently induce regulatory T cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI106779-01A1
Application #
8681113
Study Section
Vaccines Against Microbial Diseases (VMD)
Program Officer
Lacourciere, Karen A
Project Start
2014-02-07
Project End
2016-01-31
Budget Start
2014-02-07
Budget End
2015-01-31
Support Year
1
Fiscal Year
2014
Total Cost
$167,288
Indirect Cost
$54,788
Name
Colorado State University-Fort Collins
Department
Microbiology/Immun/Virology
Type
Schools of Veterinary Medicine
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523