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Vaccine. 2015 Sep 11;33(38):4782-9. doi: 10.1016/j.vaccine.2015.07.096. Epub 2015 Aug 7.

Delayed BCG vaccination results in minimal alterations in T cell immunogenicity of acellular pertussis and tetanus immunizations in HIV-exposed infants.

Author information

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.

KEYWORDS:

BCG vaccine; HIV; Infants; Pertussis; T cell; Tetanus

PMID:
26259542
PMCID:
PMC4562895
DOI:
10.1016/j.vaccine.2015.07.096
[Indexed for MEDLINE]
Free PMC Article

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