WP8

Immunological studies based on RCTs in Guinea-Bissau, The Gambia and Denmark

 Within RCTs we will explore the systemic immunological effects of MV, BCG and VAS.

Immunological effect of MV

 A 1 ml venous blood sample will be obtained at 4, 5, 9, 10, and 18 months from 600 participants in WP1 (n=400 early MV; n=200 controls) and thymus size will be assessed at 4, 5, 9 and 10 months of age. We will explore the immunological effects of early MV at 4 months and of a booster dose of MV at 9 months, and the influence of the presence of MatAb on the response to MV. We will study the in vitro cytokine response to mitogens and antigens, C-Reactive Protein (CRP), White Blood Cell differential count (WBC diff), and thymus size. We measure measles-specific antibody levels for all children in WP1. In this sub-study, we will also measure antibodies to a large range of common pathogens such as pertussis and pneumococcus using a newly developed multiplex method, to examine whether early MV raises cross-reactive antibodies and whether this relates to the presence of MatAb. Plasma and DNA will be stored for future biomarker, transcriptomic and proteomic studies.

Immunological effect of BCG

 A capillary blood sample will be collected at 3 months of age from 300 participants in WP3 (n=150 BCG; n=150 no BCG). We will examine in vitro cytokine response to mitogens and antigens (in particular stimulators of the innate immune system such as LPS, Pam3Cys, and Poly I:C), CRP, WBC diff, and thymus size. A capillary blood sample will be collected at 13 months in order to measure antibodies to common pathogens as described above to examine whether BCG raises cross-reactive antibodies. Plasma and DNA will be stored for future biomarker, transcriptomic and proteomic studies.

Immunological effect of VAS

 An RCT in The Gambia is exploring the detailed immunological effects of neonatal VAS including analyses of thymus size, tuberculin skin test reactivity, cytokine profile, regulatory T cell function, intestinal mucosal integrity, B cell and dendritic cell function. Ongoing studies in The Gambia are using whole human genome transcriptome analysis to study the NSEs of vaccines, and subsequent bioinformatic biological pathway analysis is being used to determine the wider immunological effects of vaccination. We will continue these state-of-the-art studies and extend to planned proteomic studies.

PhD students

 The first PhD student will study the immunological effects of MV. The student will be placed in Guinea-Bissau and at the Center. The PhD student will be supervised by Katie Flanagan and Christine Stabell Benn. The specific project of the second PhD student to start in 2015 will be defined according to the priorities of the Center at that time. The PhD students’ academic focus will continuously be evaluated by CVIVA's steering committee. Research results will be published in leading international journals and in conference proceedings, and in all cases, the Center and the Danish National Research Foundation be thanked for support. The PhD students will participate in all key meetings and activities of the Center and contribute to the Center's general activities.