02920nas a2200445 4500000000100000008004100001260001300042653003100055653001200086653002600098653001600124653002300140653003300163653002300196653001400219653002100233653002900254653001600283653001600299653002600315653000900341653002300350653003100373653001700404653002500421653002600446100001200472700001300484700001100497700001500508700001500523700001500538700001400553700001400567245018700581300001100768490000700779520167400786022001402460 2009 d c2009 Jan10aAdministration, Inhalation10aAnimals10aAntibodies, Bacterial10aBCG Vaccine10aBacterial Vaccines10aBronchoalveolar Lavage Fluid10aCell Proliferation10aCytokines10aImmunoglobulin A10aInjections, Subcutaneous10aLymphocytes10aMacrophages10aMacrophages, Alveolar10aMice10aMice, Inbred C57BL10aMycobacterium tuberculosis10aTuberculosis10aVaccines, Attenuated10aVaccines, Inactivated1 aGupta A1 aGeetha N1 aMani J1 aUpadhyay P1 aKatoch V M1 aNatrajan M1 aGupta U D1 aBhaskar S00aImmunogenicity and protective efficacy of "Mycobacterium w" against Mycobacterium tuberculosis in mice immunized with live versus heat-killed M. w by the aerosol or parenteral route. a223-310 v773 a

As the disease caused by Mycobacterium tuberculosis continues to be a burden, there is a concerted effort to find new vaccines to combat this problem. One of the important vaccine strategies is whole bacterial vaccines. This approach relies on multiple antigens and built-in adjuvanticity. Other mycobacterial strains which share cross-reactive antigens with M. tuberculosis have been considered as alternatives to M. bovis for vaccine use. One such strain, "Mycobacterium w", had been evaluated for its immunomodulatory properties in leprosy. A vaccine against leprosy based on killed M. w is approved for human use, where it has resulted in clinical improvement, accelerated bacterial clearance, and increased immune responses to Mycobacterium leprae antigens. M. w shares antigens not only with M. leprae but also with M. tuberculosis, and initial studies have shown that vaccination with killed M. w induces protection against tuberculosis in Mycobacterium bovis BCG responder, as well as BCG nonresponder, strains of mice. Hence, we further studied the protective potential of M. w and the underlying immune responses in the mouse model of tuberculosis. We analyzed the protective efficacy of M. w immunization in both live and killed forms through the parenteral route and by aerosol immunization, compared with that of BCG. Our findings provide evidence that M. w has potential protective efficacy against M. tuberculosis. M. w activates macrophage activity, as well as lymphocytes. M. w immunization by both the parenteral route and aerosol administration gives higher protection than BCG given by the parenteral route in the mouse model of tuberculosis.

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