Decreased survival of guinea pigs infected with Mycobacterium tuberculosis after multiple BCG vaccinations.

The BCG vaccine for tuberculosis has an outstanding safety record, with only occasional reports of adverse reactions. In some countries multiple BCG vaccinations have been given to children, but with no apparent benefit. We show here that in the highly susceptible guinea pig model of Mycobacterium tuberculosis infection animals receiving three sequential injections of BCG began to die unexpectedly at times after aerosol challenge much earlier than animals receiving the vaccine only once.

Mice fed lipid-encapsulated Mycobacterium bovis BCG are protected against aerosol challenge with Mycobacterium tuberculosis.

Mice that consumed a single dose of 10(7) lipid-encapsulated Mycobacterium bovis BCG bacilli showed significant pulmonary and systemic protection against aerosol challenge with M. tuberculosis H37Rv. As an extension of previous challenge studies with virulent strains of M.

NIH pre-clinical screening program: overview and current status.

The increase in the number of cases of Mycobacterium tuberculosis around the world has lead to a greater need for a more efficacious vaccine than the currently used M. bovis BCG. Despite the relative success of this attenuated vaccine there are multiple examples where alternative strategies are desperately needed.

The protective effect of the Mycobacterium bovis BCG vaccine is increased by coadministration with the Mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M. tuberculosis-infected guinea pigs.

A tuberculosis vaccine candidate consisting of a 72-kDa polyprotein or fusion protein based upon the Mtb32 and Mtb39 antigens of Mycobacterium tuberculosis and designated Mtb72F was tested for its protective capacity as a potential adjunct to the Mycobacterium bovis BCG vaccine in the mouse and guinea pig models of this disease. Formulation of recombinant Mtb72F (rMtb72F) in an AS02A adjuvant enhanced the Th1 response to BCG in mice but did not further reduce the bacterial load in the lungs after aerosol challenge infection. In the more stringent guinea pig disease model, rMtb72F delivered by coadministration with BCG vaccination significantly improved the survival of these animals compared to BCG alone, with some animals still alive and healthy in their appearance at >100 weeks post-aerosol challenge.

Differential immune responses and protective efficacy induced by components of a tuberculosis polyprotein vaccine, Mtb72F, delivered as naked DNA or recombinant protein.

Key Ags of Mycobacterium tuberculosis initially identified in the context of host responses in healthy purified protein derivative-positive donors and infected C57BL/6 mice were prioritized for the development of a subunit vaccine against tuberculosis. Our lead construct, Mtb72F, codes for a 72-kDa polyprotein genetically linked in tandem in the linear order Mtb32(C)-Mtb39-Mtb32(N). Immunization of C57BL/6 mice with Mtb72F DNA resulted in the generation of IFN-gamma responses directed against the first two components of the polyprotein and a strong CD8(+) T cell response directed exclusively against Mtb32(C).

Failure of the Mycobacterium bovis BCG vaccine: some species of environmental mycobacteria block multiplication of BCG and induction of protective immunity to tuberculosis.

The efficacy of Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine against pulmonary tuberculosis (TB) varies enormously in different populations. The prevailing hypothesis attributes this variation to interactions between the vaccine and mycobacteria common in the environment, but the precise mechanism has so far not been clarified. Our study demonstrates that prior exposure to live environmental mycobacteria can result in a broad immune response that is recalled rapidly after BCG vaccination and controls the multiplication of the vaccine.