The Immune Response to Mycobacterial Infection: Development of New Vaccines

Pulmonary tuberculosis continues to flourish worldwide despite our most vigorous attempts to control it. After nearly a century of study we still know very little about the virulence factors of M. tuberculosis of M. bovis or how they trigger the protective immune response within the infected host. This anti-tuberculous response is mediated by a population of specifically sensitised T lymphocytes which activate the monocytes entering the developing lesion from the bloodstream. The immunologically activated macrophage induces a persistent bacteriostasis which is usually sufficient to protect the host although it will not eliminate the infection altogether so that reactivation can occur whenever the cellular defences are depleted as a result of aging or immunosuppressive chemotherapy. Protective immunogens released by actively growing tubercle bacilli give rise to a protective cell-mediated, rather than a humoral (non-protective) immunity. The genes responsible for the production of these "protective" antigens are being cloned and transferred to suitable mycobacterial vectors by means of the newly developed "shuttle phasmid". Development of such recombinants constitute the first step in preparing more effective anti-tuberculous vaccines for future use against these important human and animal pathogens.