Max Planck Institute for Infection
Biology, Schumannstr. 21/22, 10117 Berlin
Tuberculosis is a major health
threat with 9 million new cases and 2 million deaths annually. Although a
vaccine is already available, Bacille-Calmette-Guérin (BCG), this vaccine
only protects against miliary tuberculosis in newborns and fails to prevent
the most common form of disease, pulmonary tuberculosis in adults. One third
of the world population is infected with the etiologic agent Mycobacterium
tuberculosis. Current vaccination strategies, therefore, have to consider
both pre-exposure and post-exposure vaccines and it is possible that different
vaccination strategies are required for each situation. The immune response
against Mycobacterium tuberculosis is T cell-mediated and comprises
different populations. Novel vaccination strategies, thus, have to consider
the T cell compartment as prime target. Current vaccination strategies follow
two lines: subunit vaccines and attenuated viable vaccines. Subunit vaccination
strategies comprise protein formulations or naked DNA in an appropriate
adjuvant. Viable attenuated vaccines comprise either gene deletion mutants
of M. tuberculosis or improved recombinant BCG. Rational vaccination
strategies performed in the laboratory of the author first focus on recombinant
BCG. A recombinant BCG strain which expresses listeriolysin induces better
protection than BCG wild type. Because BCG has its merits, it cannot be
given up prematurely. Hence, prime/boost vaccinations based on BCG need particular
consideration. A vaccine antigen was identified which improved BCG prime
when given as naked DNA boost vaccination. The following years will witness
the transformation of vaccine candidates from preclinical to clinical trials.
Coordination will be needed to identify the most appropriate candidates for
clinical trials which will be highly laborious and time consuming.