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

PLoS One. 2009 Dec 23;4(12):e8434. doi: 10.1371/journal.pone.0008434.

Abstract

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Protozoan / immunology
  • Child
  • Child, Preschool
  • Clone Cells
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Dosage / genetics
  • Gene Expression Regulation
  • Humans
  • Hypoxanthine Phosphoribosyltransferase / genetics
  • Immunity / genetics*
  • Infant
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Kenya
  • Malaria Vaccines / immunology*
  • Polymerase Chain Reaction*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rabies Vaccines / immunology
  • Receptors, Thrombin / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Time Factors
  • Vaccination*

Substances

  • Antigens, Protozoan
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Malaria Vaccines
  • RNA, Messenger
  • Rabies Vaccines
  • Receptors, Thrombin
  • Interferon-gamma
  • Hypoxanthine Phosphoribosyltransferase