Affiliation:
1. Bacterial Vaccine Department, Statens Seruminstitut, Copenhagen, Denmark.
Abstract
An experimental vaccine that was based on secreted proteins of Mycobacterium tuberculosis was investigated in a mouse model of tuberculosis. I used a short-term culture filtrate (ST-CF) containing proteins secreted from actively replicating bacteria grown under defined culture conditions. The immunogenicity of the ST-CF was investigated in combination with different adjuvants, and peak proliferative responses were observed when ST-CF was administered with the surface-active agent dimethyldioctadecylammonium chloride. The immunity induced by this vaccine was dose dependent, and, in the optimal concentration, the vaccine induced a potent T-helper 1 response which efficiently protected the animals against a subsequent challenge with virulent M. tuberculosis. Antigenic targets for the T cells generated were mapped by employing narrow-molecular-weight fractions of ST-CF. The experimental vaccine primed a broadly defined T-cell repertoire directed to multiple secreted antigens present in ST-CF. A vaccination with viable Mycobacterium bovis bacillus Calmette-Guérin (BCG), in contrast, induced a restricted T-cell reactivity directed to two secreted protein fractions with molecular masses of 5 to 12 and 25 to 35 kDa. The protective efficacy of the ST-CF vaccine was compared with that of a BCG standard vaccine, and both induced a highly significant protection of equal magnitude. The vaccination with ST-CF gave rise to a population of long-lived CD4 cells which could be isolated 22 weeks after the vaccination and could adoptively transfer acquired resistance to T-cell-deficient recipients. My results confirm the hypothesis that M. tuberculosis cells release protective antigens during growth. The high efficacy of a subunit vaccine observed in the present study is discussed as a possible alternative to a live recombinant vaccine carrier.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Reference51 articles.
1. The secreted antigens of Mycobacterium tuberculosis and their relationship to those recognized by the available antibodies;Abou-Zeid C.;J. Gen. Microbiol.,1988
2. Protection by BCG vaccination-a review of Australian epidemiology;Abrahams E. W.;Dev. Biol. Stand.,1986
3. Duration of immunity to tuberculosis in mice vaccinated intravenously with oil-treated cell walls of Mycobacterium bovis strain BCG;Anacker R. L.;J. Immunol.,1967
4. Identification of immunodominant antigens during infection with Mycobacterium tuberculosis;Andersen P.;Scand. J. Immunol.,1992
5. Proteins released from Mycobacterium tuberculosis during growth;Andersen P.;Infect. Immun.,1991
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