Bovine tuberculosis

Perspectives on Global Bovine Tuberculosis Control 251

peptides bind to bovine histocompatibility anti-
gen molecules will provide an unbiased, in silico
means to define the M. bovis T-cell antigenome in
cattle. Recent advances in this regard include
the report by Farrell et al. (2016) who used three
MHC-II-binding prediction methods to screen
the M. bovis proteome for potential binders to the
bovine BoLA-DRB3. Using this method, they
demonstrated significant enrichment (>24 %)
for promiscuously recognized epitopes. Even so,
it will remain a challenge to predict which anti-
gens are specific for M. bovis. The absence of a
particular protein within a genome does not
guarantee that the short antigenic region it may
contain is not shared with other intact antigens
encoded elsewhere in the genome. In silico
approaches need to be validated using the target
species, in their natural setting.
Whole blood assays for the immunological
detection of TB currently require live and fully
functional leukocytes to be delivered to the labo-
ratory for testing. This is a challenge, especially
in large or resource-poor countries with diverse
environmental conditions and under-developed
transport networks. In these settings, improved
methods to assure sample viability, or the devel-
opment of improved assays not requiring live
cells and with new fixation methods, are critical
for the use of such tests. An ‘in tube’ approach
for immediate antigen stimulation may over-
come these challenges once the logistical and
technical hurdles have been addressed for cattle
blood, in the way they have been for human
samples. Even better would be the development
of accurate point of care assays for use in the
field which might, for example, reflect cellular
changes taking place early in infection (see
Chapter 10).
Antibody-based assays are appealing due to
ease and convenience of sample collection, stor-
age and analysis. However, they generally have
insufficient sensitivity for most applications.
This has prevented widespread development and
use of these assays for the diagnosis of TB in
cattle. Currently, the best promise for developing
an improved antibody-based test is the discovery
of antigens that are recognized early after infec-
tion and preferably without the requirement for
injection of PPD for skin test to achieve detect-
able levels. Proteome-wide antigen mining for
sero-dominant antigens has yet to be under-
taken in cattle but should yield additional

relevant targets for sero-diagnosis that could

increase the sensitivity of serology to detect

tuberculous cattle.

A critical need for the next decade is to eval-

uate the emerging immunological approaches

for diagnosis in practical platforms with a wide

range of samples from naturally infected cattle

for direct comparison to existing official tests (in

particular, traditional TST and IGRAs). This

crucial need for robust validation will require

collaboration and investment from funding

agencies, biologics companies, livestock stake-

holders, policymakers and federal/regional

veterinary field staff.

16.4 Vaccination

The multi-host nature (see Chapters 6 and 7)

and environmental survival of pathogenic

mycobacteria (see Chapter 4) generates com-

plexity in a context where successful disease

control strategies will need to integrate all avail-

able tools, including biosafety and prevention,

population control where possible, and vaccina-

tion as a component intervention (see Chapter

15). While there has been progress in vaccine

development, evaluation and licensing for TB

control, there remain some considerable chal-

lenges (see Chapter 14). These relate to the

immunogenicity and safety of the vaccine and

to the practicalities of its delivery. Many of these

challenges are overlapping.

16.4.1 Microbiological

Until recently, vaccine development has been

largely empirical or involved introducing attenu-

ations used with other classes of bacteria such

as the Enterobacteriaceae. Identification of

major immunogens is under way, but a greater

in-depth analysis of the surface and other pro-

teins, carbohydrates and complexes has not been

undertaken with a view to modelling interaction

with the MHC of cattle and other species, identi-

fying those likely to initiate strong Th1 responses.

While distinct genes have been suggested as

M. bovis virulence factors (see Chapter 8),

genome-wide approaches, such as those applied

to reveal gene essentiality in M. tuberculosis