A recombinant attenuated Mycobacterium tuberculosis vaccine strain is safe in immunosuppressed simian immunodeficiency virus-infected infant macaques

Kara Jensen, Uma Devi K. Ranganathan, Koen K.A. Van Rompay, Don R. Canfield, Imran Khan, Resmi Ravindran, Paul A. Luciw, William R. Jacobs, Glenn Fennelly, Michelle H. Larsen, Kristina Abel

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Many resource-poor countries are faced with concurrent epidemics of AIDS and tuberculosis (TB) caused by human immunodeficiency virus (HIV) and Mycobacterium tuberculosis, respectively. Dual infections with HIV andM. tuberculosis are especially severe in infants. There is, however, no effective HIV vaccine, and the only licensed TB vaccine, the Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine, can cause disseminated mycobacterial disease in HIV-infected children. Thus, a pediatric vaccine to prevent HIV andM. tuberculosis infections is urgently needed. We hypothesized that a highly attenuatedM. tuberculosis 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 immuno-compromised hosts. Of three vaccine candidates tested, the recombinant attenuatedM. tuberculosis strain mc 26435 carrying a simian immunodeficiency virus (SIV) Gag expression plasmid and harboring attenuations of genes critical for replication (panCD and leuCD) and immune evasion (secA2), 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 ofM. tuberculosis 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 attenuatedM. tuberculosis-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.

Original languageEnglish (US)
Pages (from-to)1170-1181
Number of pages12
JournalClinical and Vaccine Immunology
Volume19
Issue number8
DOIs
StatePublished - Aug 1 2012

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

Cite this

Jensen, K., Ranganathan, U. D. K., Van Rompay, K. K. A., Canfield, D. R., Khan, I., Ravindran, R., Luciw, P. A., Jacobs, W. R., Fennelly, G., Larsen, M. H., & Abel, K. (2012). A recombinant attenuated Mycobacterium tuberculosis vaccine strain is safe in immunosuppressed simian immunodeficiency virus-infected infant macaques. Clinical and Vaccine Immunology, 19(8), 1170-1181. https://doi.org/10.1128/CVI.00184-12