A neonatal oral Mycobacterium tuberculosis-SIV prime/intramuscular MVA-SIV boost combination vaccine induces both SIV and Mtb-specific immune responses in infant macaques

Kara Jensen, Myra Grace Dela Pena, Robert L. Wilson, Uma Devi K. Ranganathan, William R. Jacobs, Glenn Fennelly, Michelle Larsen, Koen K.A. Van Rompay, Pamela A. Kozlowski, Kristina Abel

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Mother-to-child-transmission of HIV by breast-feeding remains a major obstacle in the eradication of HIV infection. Compared to adults, HIV-infected infants have more rapid disease and show higher susceptibility to co-infections like tuberculosis (TB). Although the Bacille Calmette-Guérin vaccine can be administered at birth to protect against TB, BCG can disseminate in HIV-infected infants and increase mortality. Thus, a pediatric combination vaccine to stop both HIV and TB infection in infants is urgently needed. Towards the goal of developing a pediatric combination HIV-TB vaccine to prevent both oral HIV acquisition by breast-feeding and TB infection, we tested and optimized an immunization regimen using a novel live attenuated Mycobacterium tuberculosis vaccine engineered to express simian immunodeficiency (SIV) antigens followed by heterologous MVA-SIV boosting in the infant macaque model. A single oral dose of the attenuated Mtb-SIV vaccine strain mc26435 during the first week of life was sufficient to induce persistent TB-specific immune responses. SIV-specific immunity was induced at low but comparable magnitudes after oral or intradermal priming, and was enhanced following MVA-SIV boosts. T cell responses were most pronounced in intestinal tissues and oral lymph nodes. Importantly, in addition to plasma SIV-specific IgG and IgA antibodies, infant macaques developed mucosal SIV-specific IgA in saliva and intestinal IgA and IgG. While future SIV and Mtb challenge studies will be needed to determine the protective efficacy of the Mtb-SIV/MVA-SIV vaccine, infants at high risk for oral HIV acquisition by breast-feeding and TB infection could profoundly benefit from an effective combination vaccine.

Original languageEnglish (US)
Pages (from-to)53-63
Number of pages11
JournalTrials in Vaccinology
Volume2
Issue number1
DOIs
StatePublished - Nov 7 2013

Keywords

  • HIV
  • Immunogenicity
  • Neonatal macaque model
  • TB
  • Vaccine

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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