TY - JOUR
T1 - A neonatal oral Mycobacterium tuberculosis-SIV prime/intramuscular MVA-SIV boost combination vaccine induces both SIV and Mtb-specific immune responses in infant macaques
AU - Jensen, Kara
AU - Dela Pena, Myra Grace
AU - Wilson, Robert L.
AU - Ranganathan, Uma Devi K.
AU - Jacobs, William R.
AU - Fennelly, Glenn
AU - Larsen, Michelle
AU - Van Rompay, Koen K.A.
AU - Kozlowski, Pamela A.
AU - Abel, Kristina
N1 - Funding Information:
The studies were supported by NIH Grants 1R01 DE019064 (to K.A., M.L., and G.F.), T32 AI007419 and T32 AI007001-36 (to K.J.), and by the Louisiana Vaccine Center funded by the Louisiana Board of Regents (PAK) . The animal studies at the CNPRC were supported by NIH Grants RR00169 from the National Center for Research Resources (NCRR; NIH) and the Office of Research Infrastructure Programs / OD P51 OD011107 . Studies at UNC Chapel Hill were supported by the Center for AIDS Research (CFAR; NIH Grant 2 P30 AI050410 ), and by the UNC Flow Cytometry Core that receives support from the Department of Microbiology and Immunology and the NCI Center Core Support Grant P30 CA06086 to the UNC Chapel Hill Lineberger Cancer Center . We are especially grateful to Dr. B. Moss and Dr. P. Earl for providing us with the MVA-SIV vaccine vectors and to Jeffrey Americo for growth and quality control of the vaccine stocks (Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD). The SIV Gag and Env peptide pools were provided by the NIH AIDS Research and Reference Reagent Program (Division of AIDS, NIAID, NIH). Mtb antigens were provided by BEI Resources. In addition, we thank the staff of Colony Research Services, Pathology, Primate Medicine, and Clinical Laboratory at the CNPRC, and Yongzhi Geng for technical assistance in the studies.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - HIV
KW - Immunogenicity
KW - Neonatal macaque model
KW - TB
KW - Vaccine
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UR - http://www.scopus.com/inward/citedby.url?scp=84889084961&partnerID=8YFLogxK
U2 - 10.1016/j.trivac.2013.09.005
DO - 10.1016/j.trivac.2013.09.005
M3 - Article
AN - SCOPUS:84889084961
SN - 1879-4378
VL - 2
SP - 53
EP - 63
JO - Trials in Vaccinology
JF - Trials in Vaccinology
IS - 1
ER -
