Anna K Blakney1, Christophe Toukam Tchakoute2, Anneke C Hesseling3, Elvis B Kidzeru2, Christine E Jones4, Jo-Ann S Passmore5, Donald L Sodora6, Clive M Gray7, Heather B Jaspan8. 1. Department of Bioengineering, University of Washington, United States; Division of Immunology, Institute of Infectious Disease and Molecular Medicine and Clinical Laboratory Sciences, University of Cape Town, South Africa. 2. Division of Immunology, Institute of Infectious Disease and Molecular Medicine and Clinical Laboratory Sciences, University of Cape Town, South Africa. 3. Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. 4. Division of Immunology, Institute of Infectious Disease and Molecular Medicine and Clinical Laboratory Sciences, University of Cape Town, South Africa; Paediatric Infectious Diseases Research Group, St George's, University of London, UK. 5. Division of Medical Virology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town and National Health Laboratory Services, South Africa. 6. Center for Infectious Disease Research (Formerly Seattle Biomed), Seattle, WA, United States. 7. Division of Immunology, Institute of Infectious Disease and Molecular Medicine and Clinical Laboratory Sciences, University of Cape Town, South Africa; National Health Laboratory Services, Groote Schuur Hospital, Cape Town, South Africa. 8. Division of Immunology, Institute of Infectious Disease and Molecular Medicine and Clinical Laboratory Sciences, University of Cape Town, South Africa; Seattle Children's Research Institute and Departments of Pediatrics and Global Health, University of WA, Seattle, WA, United States. Electronic address: hbjaspan@gmail.com.
Abstract
BACKGROUND:Bacille Calmette-Guerin (BCG) is effective in preventing disseminated tuberculosis (TB) in children but may also have non-specific benefits, and is thought to improve immunity to unrelated antigens through trained innate immunity. In HIV-infected infants, there is a risk of BCG-associated adverse events. We aimed to explore whether delaying BCG vaccination by 8 weeks, in utero or perinatal HIV infection is excluded, affected T-cell responses to B. pertussis (BP) and tetanus toxoid (TT), in HIV-exposed, uninfected infants. METHODS: Infants were randomized to receive BCG vaccination at birth or 8 weeks of age. At 8 and 14 weeks, T cell proliferation and intracellular cytokine (IL-2, IL-13, IL-17, and IFN-γ) expression was analyzed in response to BP, TT and Staphylococcal enterotoxin B (SEB) antigens. RESULTS: Delaying BCG vaccination did not alter T-cell proliferation to BP or TT antigens. Infants immunized with BCG at birth had higher CD4+ T cell proliferation to SEB at 14 weeks of age (p=0.018). Birth-vaccinated infants had increased CD8+ IL-2 expression in response to BP, but not TT or SEB, at 8 weeks. Infants vaccinated with BCG at 8 weeks had significantly lower IL-13 expression by BP-specific CD4+ and CD8+ T cells at 14 weeks (p=0.032 and p=0.0035, respectively). There were no observed differences in multifunctional cytokine response to TT, BP or SEB between infants vaccinated with BCG at birth versus 8 weeks of age. CONCLUSION: Delaying BCG vaccination until 8 weeks of age results in robust T-cellular responses to BP and TT in HIV-exposed infants. CLINICAL TRIAL REGISTRY: NCT02062580.
RCT Entities:
BACKGROUND: Bacille Calmette-Guerin (BCG) is effective in preventing disseminated tuberculosis (TB) in children but may also have non-specific benefits, and is thought to improve immunity to unrelated antigens through trained innate immunity. In HIV-infectedinfants, there is a risk of BCG-associated adverse events. We aimed to explore whether delaying BCG vaccination by 8 weeks, in utero or perinatal HIV infection is excluded, affected T-cell responses to B. pertussis (BP) and tetanus toxoid (TT), in HIV-exposed, uninfected infants. METHODS:Infants were randomized to receive BCG vaccination at birth or 8 weeks of age. At 8 and 14 weeks, T cell proliferation and intracellular cytokine (IL-2, IL-13, IL-17, and IFN-γ) expression was analyzed in response to BP, TT and Staphylococcal enterotoxin B (SEB) antigens. RESULTS: Delaying BCG vaccination did not alter T-cell proliferation to BP or TT antigens. Infants immunized with BCG at birth had higher CD4+ T cell proliferation to SEB at 14 weeks of age (p=0.018). Birth-vaccinated infants had increased CD8+ IL-2 expression in response to BP, but not TT or SEB, at 8 weeks. Infants vaccinated with BCG at 8 weeks had significantly lower IL-13 expression by BP-specific CD4+ and CD8+ T cells at 14 weeks (p=0.032 and p=0.0035, respectively). There were no observed differences in multifunctional cytokine response to TT, BP or SEB between infants vaccinated with BCG at birth versus 8 weeks of age. CONCLUSION: Delaying BCG vaccination until 8 weeks of age results in robust T-cellular responses to BP and TT in HIV-exposed infants. CLINICAL TRIAL REGISTRY: NCT02062580.
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