Analysis of the B cell responsiveness to the TLR9 agonist CPG in malaria semi-immune versus malaria naïve individuals
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1
Malaria Research and Craining Center(MRTC)/USTTB, Laboratory of Immunogenetics, Mali
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2
NIH, Malaria Infection Biology, Laboratory of Immunogenetics, United States
In the context of Phase 1 clinical trials of the malaria vaccine candidate AMA1 we found that the novel vaccine adjuvant CPG, TLR9 agonist that activates memory B cells, enhanced the antibody and memory B cell response to AMA1 in malaria-naïve U.S. adults, but not in malaria-immune Malian adults, suggesting that chronic P. falciparum exposure leads to TLR9 refractoriness. To follow up on this clinical observation we are conducting a systematic ex vivo analysis in which we compare the phenotype and function of memory B cells obtained from malaria-experienced and naïve individuals. In response to CPG stimulation we measure B cell proliferation, immunoglobulin class switching, cytokine production, antibodies secretion and the expression of co- stimulatory molecules. Male and female at age of 18 or greater from malaria endemic village are equally enrolled. Adult from malaria free area are used as control. Our preliminary results showed that both naïve and memory B cells from malaria semi-immune individuals respond less to CPG stimulation compared to malaria naïve individuals. Also malaria semi-immune individuals have a greater expression of the costimulatory molecule CD86. The next step will consist of comparing the above variables among 30 infected individuals, 30 uninfected individuals from Mali and 30 naïve individuals from the USA.
The results from this study may highlight the importance of testing the efficacy of novel vaccine adjuvants in the target population and may also provide fundamental insights into how chronic P. falciparum exposure modulates the innate immune response.
Acknowledgements
Volonteers from Kambila (Mali)
Volunteers from USA
National Institute of Health (NIH)
Malaria Reseach and Training Center (MRTC)
Keywords:
Malaria,
innate immunity,
TLR9,
B cells,
Vaccines
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Kone
Y,
Niare
D,
Doumtabe
D,
Kayentao
K,
Ongoiba
A,
Portugal
S,
Moebius
J,
Pierce
S,
Doumbo
O,
Crompton
P and
Traore
B
(2013). Analysis of the B cell responsiveness to the TLR9 agonist CPG in malaria semi-immune versus malaria naïve individuals.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00837
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Received:
19 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Younoussou Kone, Malaria Research and Craining Center(MRTC)/USTTB, Laboratory of Immunogenetics, Bamako, 1805, Mali, ykone@icermali.org