期刊
FRONTIERS IN IMMUNOLOGY
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2017.01551
关键词
vaccines; clinical trials; malaria; cellular immune response; cytokines
类别
资金
- European and Developing Countries Clinical Trials Partnership (EDCTP) [SP.2011.41304.025]
- Swedish International Development Cooperation Agency (Sida)
- UK Medical Research Council
- Irish Aid, Department of Foreign Affairs and Trade, Ireland
- Bundesministerium fur Bildung und Forschung (BMBF), Germany
- Wellcome Trust
- UK National Institute of Health Research
- UK Medical Research Council (MRC)
- UK Department for International Development (DFID) under the MRC/DFID [MC_UP_A900/1122]
- Medical Research Council [MC_UP_A900_1122] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0514-10158] Funding Source: researchfish
- Wellcome Trust [104750/Z/14/Z] Funding Source: researchfish
- MRC [MC_UP_A900_1118, MC_UP_A900_1122] Funding Source: UKRI
Background: Heterologous prime-boost vaccination with chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) encoding multiple epitope string thrombospondin-related adhesion protein (ME-TRAP) has shown acceptable safety and promising immunogenicity in African adult and pediatric populations. If licensed, this vaccine could be given to infants receiving routine childhood immunizations. We therefore evaluated responses to ChAd63 MVA ME-TRAP when co-administered with routine Expanded Program on Immunization (EPI) vaccines. Methods: We enrolled 65 Gambian infants and neonates, aged 16, 8, or 1 week at first vaccination and randomized them to receive either ME-TRAP and EPI vaccines or EPI vaccines only. Safety was assessed by the description of vaccine-related adverse events (AEs). Immunogenicity was evaluated using IFN gamma enzyme-linked immunospot, whole-blood flow cytometry, and anti-TRAP IgG ELISA. Serology was performed to confirm all infants achieved protective titers to EPI vaccines. Results: The vaccines were well tolerated in all age groups with no vaccine-related serious AEs. High-level TRAP-specific IgG and T cell responses were generated after boosting with MVA. CD8(+) T cell responses, previously found to correlate with protection, were induced in all groups. Antibody responses to EPI vaccines were not altered significantly. Conclusion: Malaria vectored prime-boost vaccines co-administered with routine childhood immunizations were well tolerated. Potent humoral and cellular immunity induced by ChAd63 MVA ME-TRAP did not reduce the immunogenicity of co-administered EPI vaccines, supporting further evaluation of this regimen in infant populations.
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