title: BCG vaccination induces HIV target cell activation in HIV-exposed infants in a randomized trial.
abstract: BACKGROUND.Bacillus Calmette-Guérin (BCG) vaccine is administered at birth to protect infants against tuberculosis throughout Africa, where most perinatal HIV-1 transmission occurs. We examined whether BCG vaccination alters the levels of activated HIV target T cells in HIV-exposed South African infants.METHODS.HIV-exposed infants were randomized to receive routine (at birth) or delayed (at 8 weeks) BCG vaccination. Activated and CCR5-expressing peripheral blood CD4+T cell, monocyte, and NK cell frequencies were evaluated by flow cytometry and immune gene expression via PCR using Biomark (Fluidigm).RESULTS.Of 149 infants randomized, 92% (n= 137) were retained at 6 weeks: 71 in the routine BCG arm and 66 in the delayed arm. Routine BCG vaccination led to a 3-fold increase in systemic activation of HIV target CD4+CCR5+T cells (HLA-DR+CD38+) at 6 weeks (0.25% at birth versus 0.08% in delayed vaccination groups;P= 0.029), which persisted until 8 weeks of age when the delayed arm was vaccinated. Vaccination of the infants in the delayed arm at 8 weeks resulted in a similar increase in activated CD4+CCR5+T cells. The increase in activated T cells was associated with increased levels of MHC class II transactivator (CIITA), IL12RB1, and IFN-α1 transcripts within peripheral blood mononuclear cells but minimal changes in innate cells.CONCLUSION.BCG vaccination induces immune changes in HIV-exposed infants, including an increase in the proportion of activated CCR5+CD4+HIV target cells. These findings provide insight into optimal BCG vaccine timing to minimize the risks of HIV transmissions to exposed infants while preserving potential benefits conferred by BCG vaccination.TRIAL REGISTRATION.ClinicalTrials.gov NCT02062580.FUNDING.This trial was sponsored by the Elizabeth Glaser Pediatric AIDS Foundation (MV-00-9-900-01871-0-00) and the Thrasher Foundation (NR-0095); for details, see Acknowledgments.
authors.affiliation: University of Washington, Seattle, Washington, USA.|Center for Infectious Disease Research, Seattle, Washington, USA.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Gasper
authors.affiliation: Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
authors.forename: Anneke C
authors.initials: AC
authors.lastname: Hesseling
authors.affiliation: Center for Infectious Disease Research, Seattle, Washington, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Mohar
authors.affiliation: Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, and.
authors.forename: Landon
authors.initials: L
authors.lastname: Myer
authors.affiliation: Center for Infectious Disease Research, Seattle, Washington, USA.
authors.forename: Tali
authors.initials: T
authors.lastname: Azenkot
authors.affiliation: Department of Pathology, University of Cape Town, Cape Town, South Africa.|National Health Laboratory Service, Cape Town, South Africa.
authors.forename: Jo-Ann S
authors.initials: JS
authors.lastname: Passmore
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Willem
authors.initials: W
authors.lastname: Hanekom
authors.affiliation: Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Cotton
authors.affiliation: University of Washington, Seattle, Washington, USA.|Center for Infectious Disease Research, Seattle, Washington, USA.
authors.forename: I Nicholas
authors.initials: IN
authors.lastname: Crispe
authors.affiliation: University of Washington, Seattle, Washington, USA.|Center for Infectious Disease Research, Seattle, Washington, USA.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Sodora
authors.affiliation: University of Washington, Seattle, Washington, USA.|Center for Infectious Disease Research, Seattle, Washington, USA.|Department of Pathology, University of Cape Town, Cape Town, South Africa.
authors.forename: Heather B
authors.initials: HB
authors.lastname: Jaspan
mesh_terms: D001500:BCG Vaccine / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D005260:Female; D006678:HIV; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D007231:Infant, Newborn; D008213:Lymphocyte Activation; D008297:Male; D013019:South Africa; D014376:Tuberculosis / Q000517:prevention & control
chemical_list: D001500:BCG Vaccine; D016207:Cytokines