02624nas a2200349   4500000000100000008004100001260001300042653001200055653002600067653002300093653002300116653002000139653001600159653001700175653000900192653002400201653002300225653002400248653002500272653002400297653001900321100001700340700001700357700001600374700001400390700001600404245015700420300001200577490000700589520166400596022001402260       1996                            d  c1996 Jun10aAnimals10aAntibodies, Bacterial10aBacterial Proteins10aBacterial Vaccines10aGenetic Vectors10aGuinea Pigs10aImmunization10aMice10aMice, Inbred BALB C10aMice, Inbred C57BL10aMycobacterium bovis10aMycobacterium leprae10aVaccines, Synthetic10aVaccinia virus1 aBaumgart K W1 aMcKenzie K R1 aRadford A J1 aRamshaw I1 aBritton W J00aImmunogenicity and protection studies with recombinant mycobacteria and vaccinia vectors coexpressing the 18-kilodalton protein of Mycobacterium leprae.  a2274-810 v643 a<p>The activation of antigen-specific T lymphocytes is essential for the control of leprosy infection in humans and experimental animals. T cells recognize a variety of protein antigens from Mycobacterium leprae, including the 18-kDa protein, which is limited in distribution among mycobacteria and which is absent from Mycobacterium tuberculosis and the vaccine strain, Mycobacterium bovis BCG. Adjuvant preparations of mycobacterial protein antigens have had limited protective efficacy for experimental infections in animals. Since recombinant vectors may elicit more effective T-cell responses than adjuvant preparations, recombinant vaccinia virus (VV18) and M. bovis BCG (BCG18) vectors expressing the 18-kDa protein of M. leprae were prepared. Both VV18 and BCG18 stimulated anti-18-kDa protein antibody and lymphocyte proliferative responses. Sequential immunization with VV18 followed by BCG18 induced higher levels of specific immunoglobulin G2a antibodies than immunoglobulin G1 antibodies, in contrast to immunization with VV18 or BCG18 alone. The protective efficacy of immunization with VV18 from a challenge with BCG18 was examined in two murine models of mycobacterial infection. After intravenous challenge, mice immunized with recombinant vaccinia virus exhibited lower initial levels of replication and earlier clearance of BCG18 from their spleens than mice immunized with vaccinia virus expressing an unrelated protein. After footpad infection in a dissemination model, there was earlier clearance of BCG18 from specifically immunized mice. However, immunization of mice with VV18 did not prevent a productive mycobacterial infection.</p>  a0019-9567