A second-generation anti TB vaccine is long overdue

Abstract

Mycobacterium bovis BCG vaccine significantly reduces the risk of tuberculosis by 50% and continues to be used to prevent tuberculosis around the world. However, it has been shown to be ineffective in some geographical regions. The existence of different BCG strains was described more than 60 years ago, these vary in their antigenic content but the genetic mutations in BCG strains have yet been shown to affect their protection. After the declaration of tuberculosis as a global emergency in 1993, current research attempts to develop a novel more-effective vaccine. Using new technologies, recombinant, auxotroph, DNA, subunit and phylogenetically closely related mycobacteria, naturally or genetically attenuated, have been used as vaccines in animal models, but their protective efficacy, is less than that offered by the current BCG vaccine. Today it is mandatory that a major effort be made to understand how different BCG vaccine strains influence immune response and why in some cases vaccines have failed, so we can rationally develop the next generation of tuberculosis vaccines to reduce the prevalence from 10% to less than 2 % for developed countries.

Figure 1

Documented evolution of the four M. bovis BCG strains currently licensed to produce for use in humans by the World Health Organization. The arrows indicate the chronologic evolution of Japanese and Danish strains from the original BCG Pasteur 1921 and Glaxo strain from Danish 1331. Boxes indicate occurrence of deletions of the genome during derivation of BCG. The year of derivation are indicated by (). The number in the arrows is the in vitro passages documented to have occurred during the evolution of BCG Pasteur and daughter strains since 1921 to the freeze dried of BCG in 60^th.

Figure 2

Representative cross-sections from lungs of BALB/c mice vaccinated and infected with virulent Mycobacterium tuberculosis H37Rv. A. Typical lung section from health non infected mice, no pneumonic or infiltrate were detected. B. Lung from mice non vaccinated and challenge with M. tuberculosis. C. Lung from mice vaccinated with heat inactivated Mycobacterium vaccae a closely related Mycobacterial strains. D. Lung from mice vaccinated with BCG Phipps strain. Significant reduction in the tissue damage was seen only in the mice vaccinated with BCG, the use of saprophytic bacilli as vaccine no induce immune response capable to control infection and pneumonic development. Vaccines were evaluated under a mice model of pulmonary tuberculosis (unpublished data) (H:E stain 50×).