Quantitative PCR evaluation of cellular immune responses in Kenyan children vaccinated with a candidate malaria vaccine.

Journal article

BACKGROUND: The T-cell mediated immune response plays a central role in the control of malaria after natural infection or vaccination. There is increasing evidence that T-cell responses are heterogeneous and that both the quality of the immune response and the balance between pro-inflammatory and regulatory T-cells determines the outcome of an infection. As Malaria parasites have been shown to induce immunosuppressive responses to the parasite and non-related antigens this study examined T-cell mediated pro-inflammatory and regulatory immune responses induced by malaria vaccination in children in an endemic area to determine if these responses were associated with vaccine immunogenicity. METHODS: Using real-time RT- PCR we profiled the expression of a panel of key markers of immunogenecity at different time points after vaccination with two viral vector vaccines expressing the malaria TRAP antigen (FP9-TRAP and MVA-TRAP) or following rabies vaccination as a control. PRINCIPAL FINDINGS: The vaccine induced modest levels of IFN-gamma mRNA one week after vaccination. There was also an increase in FoxP3 mRNA expression in both TRAP stimulated and media stimulated cells in the FFM ME-TRAP vaccine group; however, this may have been driven by natural exposure to parasite rather than by vaccination. CONCLUSION: Quantitative PCR is a useful method for evaluating vaccine induced cell mediated immune responses in frozen PBMC from children in a malaria endemic country. Future studies should seek to use vaccine vectors that increase the magnitude and quality of the IFN-gamma immune response in naturally exposed populations and should monitor the induction of a regulatory T cell response.

Authors: Mwacharo, J; Dunachie, S; Kai, O; Hill, A; Bejon, P

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Public Library of Science
• Journal: PloS one
• Volume: 4
• Issue: 12
• Article number: e8434
• Publication date: 2009-01-01
• DOI: 10.1371/journal.pone.0008434
• EISSN: 1932-6203
• ISSN: 1932-6203
• Language: English
• Keywords: T-Lymphocytes; Kenya; Time Factors; Vaccination; Immunity; Gene Dosage; Infant; Rabies Vaccines; Antigens, Protozoan; Polymerase Chain Reaction; Forkhead Transcription Factors; Humans; Hypoxanthine Phosphoribosyltransferase; Gene Expression Regulation; Child; Clone Cells; Child, Preschool; Interferon-gamma; Receptors, Thrombin; Malaria Vaccines; RNA, Messenger