Delayed BCG immunization does not alter antibody responses to EPI vaccines in HIV-exposed and -unexposed South African infants

Anneke C Hesseling; Anna K Blakney; Christine E Jones; Monika M Esser; Corena de Beer; Louise Kuhn; Mark F Cotton; Heather B Jaspan

doi:10.1016/j.vaccine.2016.03.081

Delayed BCG immunization does not alter antibody responses to EPI vaccines in HIV-exposed and -unexposed South African infants

Vaccine. 2016 Jul 12;34(32):3702-9. doi: 10.1016/j.vaccine.2016.03.081. Epub 2016 Apr 4.

Authors

Anneke C Hesseling¹, Anna K Blakney², Christine E Jones³, Monika M Esser⁴, Corena de Beer⁵, Louise Kuhn⁶, Mark F Cotton⁷, Heather B Jaspan⁸

Affiliations

¹ Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa. Electronic address: annekeh@sun.ac.za.
² Division of Immunology, Institute of Infectious Disease and Molecular Medicine and Clinical Laboratory Sciences, University of Cape Town, South Africa; Department of Bioengineering, University of Washington, Seattle, WA, USA.
³ 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, Institute for Infection and Immunity, St. George's, University of London, Cranmer Terrace, London SW17 0RE, UK; Department of Academic Paediatrics, Imperial College London, Norfolk Place, London W2 1NY, UK.
⁴ Immunology Unit, Division of Medical Microbiology, Department of Pathology, National Health Laboratory Service, University of Stellenbosch, Cape Town, South Africa.
⁵ Division of Medical Virology, Department of Pathology, National Health Laboratory Service, Stellenbosch University, South Africa.
⁶ Gertrude H. Sergievsky Center, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, New York, NY, USA.
⁷ Children's Infectious Diseases Clinical Research Unit, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, 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 Washington, Seattle, WA, USA.

PMID: 27055019
DOI: 10.1016/j.vaccine.2016.03.081

Abstract

Background: Bacille Calmette-Guérin (BCG) is routinely given at birth in tuberculosis-endemic settings due to its protective effect against disseminated tuberculosis in infants. BCG is however contraindicated in HIV-infected infants. We investigated whether delaying BCG vaccination to 14 weeks of age affected vaccine-induced antibody responses to Haemophilus influenzae type b (Hib)-conjugate, pertussis, tetanus and Hepatitis B (HBV) vaccines, in HIV-exposed uninfected (HEU) and -unexposed uninfected (HUU) infants.

Methods: Infants were randomized to receive BCG at birth or at 14 weeks of age. Blood was taken at 14, 24, and 52 weeks of age and analyzed for Hib, pertussis, tetanus and HBV specific antibodies.

Results: BCG was given either at birth (106 infants, 51 HEU) or at 14 weeks of age (74 infants, 50 HEU). The timing of BCG vaccination did not influence the antibody response to any antigen studied. However, in a non-randomized comparison, HEU infants had higher Hib antibody concentrations at weeks 14 and 24 (p=0.001 and <0.001, respectively) and pertussis at week 24 (p=0.003). Conversely, HEU infants had lower antibody concentrations to HBV at 14 and 52 weeks (p=0.032 and p=0.031) with no differences in tetanus titres.

Conclusions: HIV exposure, but not the timing of BCG vaccination, was associated with antibody concentrations to Hib, pertussis, HBV and tetanus primary immunization.

Clinical trial registration: DOH-27-1106-1520.

Keywords: BCG; HIV-exposed; Humoral immunity; Infants; South Africa.

Publication types

Clinical Trial, Phase II
Randomized Controlled Trial
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Bacterial / blood
Antibodies, Viral / blood
Antibody Formation
BCG Vaccine / administration & dosage*
BCG Vaccine / therapeutic use
Diphtheria-Tetanus-Pertussis Vaccine / therapeutic use*
Female
HIV Infections*
Haemophilus Vaccines / therapeutic use*
Humans
Immunization Schedule*
Infant
Infant, Newborn
Infectious Disease Transmission, Vertical
Male
Poliovirus Vaccine, Oral / therapeutic use*
Pregnancy
Single-Blind Method
South Africa
Tetanus Toxoid / therapeutic use*
Time Factors

Substances

Antibodies, Bacterial
Antibodies, Viral
BCG Vaccine
Diphtheria-Tetanus-Pertussis Vaccine
Haemophilus Vaccines
Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate
Poliovirus Vaccine, Oral
Tetanus Toxoid
diphtheria-tetanus-pertussis-haemophilus b conjugate vaccine