The Impact of Immune Activation on Infant BCG Vaccine Response 公开
Patterson, Naomi (Spring 2018)
Published
Abstract
BACKGROUND:
Tuberculosis (TB) is a major cause of morbidity and mortality in children. Bacillus Calmette Guérin (BCG) is the only vaccine currently available to prevent TB, but limited vaccine efficacy has not curbed the TB epidemic. Immune activation has been linked to decreased immune responses to live vaccines. However, the relationship between immune activation and BCG response is unknown. Using an existing cohort of Kenyan human immunodeficiency virus (HIV)-uninfected mothers and their infants, we aim to determine how immune activation among mothers and infants at birth relates to infant BCG vaccine response at 10 weeks of age.
METHODS:
Pregnant women were enrolled at Kisumu County Hospital, Kisumu, Kenya, and mother-infant pairs were followed for 10 weeks from January through December 2014. Socio-demographic and clinical data were collected from mothers upon enrollment. Whole blood samples were collected from mothers and infants at delivery and stimulated in vitro with BCG or un-stimulated for 12 hours and then cryopreserved. Later, flow cytometry was used to count and type T lymphocyte cells as CD4+, CD8+, and/or KI67+. We assessed Pearson’s correlations and performed multivariable linear regression to evaluate the relationship between infant immune activation and infant BCG vaccine response at 10 weeks.
RESULTS AND DISCUSSION:
Of 395 mother-infant pairs enrolled, 46 mothers and infants had samples collected to evaluate for immune activation at delivery. Infant immune activation at birth was associated with maternal immune activation at delivery (r=0.357, p= 0.015). Maternal number of doses of sulfadoxine-pyrimethamine (SP) for malaria intermittent preventive therapy (IPT) was associated with lower infant immune activation at birth (r=-0.323, p= 0.029) and a trend toward higher BCG vaccine response at 10 weeks of life (r=0.256, p=0.086). Maternal de-worming with mebendazole or the number of tetanus boosters during pregnancy were not associated with infant immune activation at birth. After adjusting for the number of antimalarial IPT doses, infant immune activation was not associated with BCG vaccine response at 10 weeks of life.
CONCLUSION:
We found that infant immune activation detected by the frequency of KI67+CD4+ T cells was not associated with BCG vaccine response. Maternal malaria preventive therapy was associated with infant immune activation.
Table of Contents
➢ Abstract
➢ Chapter 1 – Introduction ………………………………………………………………… 1
➢ Chapter 2 – Literature Review ………………………………………………………… 7
➢ Chapter 3 – Methods and Results …………………………………………………….. 15
oMethods ……………………….……………………………………………………... 15
oResults ……………………….……………………………………………………….. 20
➢ Chapter 4 – Discussion, Conclusion and Recommendations ………........... 24
oDiscussion……………………………………………………………………………. 24
oConclusion…………………………………………………………………………… 29
oRecommendations……………………………………………………………….. 30
➢ References …………………………………………………………………………………….. 32
➢ Figures ………………………………………………………………………………………….. 35
➢ Tables……………………………………………………………………………………………. 40
➢ Appendices ……………………………………………………………………………….…... 45
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