A neonatal oralMycobacterium tuberculosis-SIV prime / intramuscular MVA-SIV boost combination vaccine induces both SIV andMtb-specific immune responses in infant macaques.
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 attenuatedMycobacterium tuberculosisvaccine engineered to express simian immunodeficiency (SIV) antigens followed by heterologous MVA-SIV boosting in the infant macaque model. A single oral dose of the attenuatedMtb-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 andMtbchallenge studies will be needed to determine the protective efficacy of theMtb-SIV / MVA-SIV vaccine, infants at high risk for oral HIV acquisition by breast-feedingandTB infection could profoundly benefit from an effective combination vaccine.
Department of Microbiology and Immunology, and Center for AIDS Research, School of Medicine, University of North Carolina at Chapel Hill, NC, United States.
Kara
K
Jensen
Department of Microbiology and Immunology, and Center for AIDS Research, School of Medicine, University of North Carolina at Chapel Hill, NC, United States.
Myra Grace Dela
MG
Pena
Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA.
Robert L
RL
Wilson
Albert Einstein College of Medicine, New York, United States.
Uma Devi K
UD
Ranganathan
Albert Einstein College of Medicine, New York, United States.
William R
WR
Jacobs
Albert Einstein College of Medicine, New York, United States.
Glenn
G
Fennelly
Albert Einstein College of Medicine, New York, United States.
Michelle
M
Larsen
California National Primate Research Center, University of California at Davis, CA, United States.
Koen K A
KK
Van Rompay
Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA.
Pamela A
PA
Kozlowski
Department of Microbiology and Immunology, and Center for AIDS Research, School of Medicine, University of North Carolina at Chapel Hill, NC, United States.
Kristina
K
Abel