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


RESULTS
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.


CONCLUSIONS
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.
Mwacharo
Jedidah
J
Centre for Geographical Medical Research, Kenya Medical Research Institute, Kilifi, Kenya. JMwacharo@kilifi.kemri-wellcome.org
Dunachie
Susanna J
SJ
Kai
Oscar
O
Hill
Adrian V S
AV
Bejon
Philip
P
Fletcher
Helen A
HA
D000953:Antigens, Protozoan / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D018628:Gene Dosage / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007109:Immunity / Q000235:genetics*; D007223:Infant; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007630:Kenya; D017780:Malaria Vaccines / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011819:Rabies Vaccines / Q000276:immunology; D018179:Receptors, Thrombin / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D014611:Vaccination
D000953:Antigens, Protozoan; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D017780:Malaria Vaccines; D012333:RNA, Messenger; D011819:Rabies Vaccines; D018179:Receptors, Thrombin; D007371:Interferon-gamma; D007041:Hypoxanthine Phosphoribosyltransferase