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Title: The influence of maternal HIV and Mycobacterium tuberculosis infection on infant immune responses to childhood vaccinations
Author: Jones, Christine Elizabeth
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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Background: Altered immune responses might contribute to the high morbidity and mortality observed amongst uninfected infants exposed to human immunodeficiency virus-1 (HIV) in utero. This study examined the influence of maternal HIV and Mycobacterium tuberculosis (Mtb) infection on infant immune responses to immunisation. Methods: 109 mother-infant pairs were enrolled from Khayelitsha, Cape Town, South Africa, and were followed for four months. Peripheral blood samples were collected from mother-infant pairs at delivery and from infants at 16 weeks of age, following routine immunisations. Responses to BCG antigens were measured using multi-parameter flow cytometry and multiplex enzyme-linked immunosorbent assays (ELISAs). Specific antibody levels to Haemophilus influenzae type B (Hib), pneumococcus, Bordetella pertussis, tetanus toxoid and hepatitis B surface antigen were determined by ELISA. Results: At birth, HIV-exposed, uninfected infants had increased frequencies of proliferating T cells expressing TNF-α and increased levels of TNF-α protein in cell culture supernatants; levels were highest amongst HIV-exposed infants born to Mtb sensitised mothers. IFN-γ levels were lower amongst HIV-exposed, uninfected infants compared to unexposed infants. Maternal Mtb sensitisation was associated with increased infant IFN-γ levels at birth; infants born to HIV-infected, Mtb-sensitised mothers had similar levels IFN-γ compared to unexposed infants. Following BCG vaccination at 6 weeks of age, the immune response to infant BCG vaccination was unaffected by maternal HIV infection of Mtb sensitisation. Amongst mothers, Mtb sensitisation significantly influenced the response to BCG-antigens in HIV-infected but not in HIV-uninfected mothers. HIV-exposed, uninfected infants had lower specific antibody responses compared with unexposed infants at birth, but had robust responses following immunisation. Deficits in humoral protection against vaccine-preventable diseases were observed amongst HIV infected and HIV-uninfected women. Conclusions: Antenatal HIV exposure was associated with alterations in immune response to vaccine antigens at birth, however HIV-exposed infants had comparable potentical to respond to immunisation.
Supervisor: Kampmann, Beate ; Wilkinson, Robert Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available