|dc.description.abstract||Approximately one-third of the global population is infected with tuberculosis causing
approximately 1.7 million deaths. Currently, the BCG vaccine is used to protect
against TB, but it cannot prevent primary infection or reactivation of latent infection.
Ideally a vaccine should protect against a diverse array of Mycobacterium
tuberculosis strains and promote a strong, long-lasting TH1 cell-mediated immune
response. Whilst evaluating the efficiency of novel vaccines using laboratory control
strains (M. tuberculosis H37Rv, H37Ra and M. bovis-BCG), it is important to test
efficacy against a representative panel of wild-type circulating strains. In England
42.2% of TB cases are reported in London and the diversity of nationalities generates
a diverse pool of strains consisting of globally representative TB strains. The aim of
the study was to construct a representative panel of strains for vaccine evaluation
studies and general TB research.
Common M. tuberculosis strains were identified by performing molecular MIRUVNTR
and spoligotyping on 2363 isolates from TB cases reported in London during a
one-year period. Epidemiological analysis demonstrated there were representatives
from 13 global regions, including high TB burden countries. An algorithm was
designed to select strains for a preliminary panel based on associations between
MTBC families in clusters of more common strains, the country of birth and VNTR
sub-clusters. The preliminary panel contained 42 MTBC strains belonging to 10
MTBC families from patients born in 17 countries.
Results of phylogenetic analysis of all 2363 isolates was used to select a smaller panel
of strains from the preliminary panel to represent MTBC lineages to investigate if
wild-type strains were phenotypically similar. The final panel included five strains
from each of the Baker et al., 2004 M. tuberculosis lineages (M. tuberculosis Beijing,
LAM10, two CAS, EAI5 strains representing lineage I, II, III, IV, respectively) and
an M. africanum strain.
In vitro tissue culture experiments demonstrated significantly higher growth of the
Beijing strain compared to the other wild-type and laboratory strains. Higher growth
rates of this strain were also observed in a cell-free culture system. Aerosol challenge
of guinea pigs with wild-type strains showed a quicker dissemination of the EAI5 strain from the lung to the spleen 16 days post-challenge, but significantly higher
c.f.u. count of the Beijing strain in the spleen 56 days post-challenge. Collectively, the
data demonstrated that there are phenotypic differences between wild-type circulating