Jensen, Kara;
Ranganathan, Uma Devi K.;
Van Rompay, Koen K. A.;
Canfield, Don R.;
Khan, Imran;
Ravindran, Resmi;
Luciw, Paul A.;
Jacobs, William R.;
Fennelly, Glenn;
Larsen, Michelle H.;
Abel, Kristina
A Recombinant Attenuated Mycobacterium tuberculosis Vaccine Strain Is Safe in Immunosuppressed Simian Immunodeficiency Virus-Infected Infant Macaques
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Medientyp:
E-Artikel
Titel:
A Recombinant Attenuated Mycobacterium tuberculosis Vaccine Strain Is Safe in Immunosuppressed Simian Immunodeficiency Virus-Infected Infant Macaques
Beteiligte:
Jensen, Kara;
Ranganathan, Uma Devi K.;
Van Rompay, Koen K. A.;
Canfield, Don R.;
Khan, Imran;
Ravindran, Resmi;
Luciw, Paul A.;
Jacobs, William R.;
Fennelly, Glenn;
Larsen, Michelle H.;
Abel, Kristina
Erschienen:
American Society for Microbiology, 2012
Beschreibung:
<jats:title>ABSTRACT</jats:title><jats:p>Many resource-poor countries are faced with concurrent epidemics of AIDS and tuberculosis (TB) caused by human immunodeficiency virus (HIV) and<jats:named-content content-type="genus-species">Mycobacterium tuberculosis</jats:named-content>, respectively. Dual infections with HIV and<jats:named-content content-type="genus-species">M. tuberculosis</jats:named-content>are especially severe in infants. There is, however, no effective HIV vaccine, and the only licensed TB vaccine, the<jats:named-content content-type="genus-species">Mycobacterium bovis</jats:named-content>bacillus Calmette-Guérin (BCG) vaccine, can cause disseminated mycobacterial disease in HIV-infected children. Thus, a pediatric vaccine to prevent HIV and<jats:named-content content-type="genus-species">M. tuberculosis</jats:named-content>infections is urgently needed. We hypothesized that a highly attenuated<jats:named-content content-type="genus-species">M. tuberculosis</jats:named-content>strain containing HIV antigens could be safely administered at birth and induce mucosal and systemic immune responses to protect against HIV and TB infections, and we rationalized that vaccine safety could be most rigorously assessed in immunocompromised hosts. Of three vaccine candidates tested, the recombinant attenuated<jats:named-content content-type="genus-species">M. tuberculosis</jats:named-content>strain mc<jats:sup>2</jats:sup>6435 carrying a simian immunodeficiency virus (SIV) Gag expression plasmid and harboring attenuations of genes critical for replication (<jats:italic>panCD</jats:italic>and<jats:italic>leuCD</jats:italic>) and immune evasion (<jats:italic>secA2</jats:italic>), was found to be safe for oral or intradermal administration to non-SIV-infected and SIV-infected infant macaques. Safety was defined as the absence of clinical symptoms, a lack of histopathological changes indicative of<jats:named-content content-type="genus-species">M. tuberculosis</jats:named-content>infection, and a lack of mycobacterial dissemination. These data represent an important step in the development of novel TB vaccines and suggest that a combination recombinant attenuated<jats:named-content content-type="genus-species">M. tuberculosis</jats:named-content>-HIV vaccine could be a safe alternative to BCG for the pediatric population as a whole and, more importantly, for the extreme at-risk group of HIV-infected infants.</jats:p>