| Autor: |
Kastenmüller, Kathrin, Espinosa, Diego A., Trager, Lauren, Stoyanov, Cristina, Salazar, Andres M., Pokalwar, Santosh, Singh, Sanjay, Dutta, Sheetij, Ockenhouse, Christian F., Zavala, Fidel, Seder, Robert A. |
| Zdroj: |
Infection and Immunity; January 2013, Vol. 81 Issue: 3 p789-800, 12p |
| Abstrakt: |
ABSTRACTThe Plasmodium falciparumcircumsporozoite (CS) protein (CSP) is a major vaccine target for preventing malaria infection. Thus, developing strong and durable antibody and T cell responses against CSP with novel immunogens and potent adjuvants may improve upon the success of current approaches. Here, we compare four distinct full-length P. falciparumCS proteins expressed in Escherichia colior Pichia pastorisfor their ability to induce immunity and protection in mice when administered with long-chain poly(I·C) [poly(I·C)LC] as an adjuvant. CS proteins expressed in E. coliinduced high-titer antibody responses against the NANP repeat region and potent CSP-specific CD4+T cell responses. Moreover, E. coli-derived CS proteins in combination with poly(I·C)LC induced potent multifunctional (interleukin 2-positive [IL-2+], tumor necrosis factor alpha-positive [TNF-a+], gamma interferon-positive [IFN-?+]) CD4+effector T cell responses in blood, in spleen, and particularly in liver. Using transgenic Plasmodium bergheiexpressing the repeat region of P. falciparumCSP [Pb-CS(Pf)], we showed that there was a 1- to 4-log decrease in malaria rRNA in the liver following a high-dose challenge and ~50% sterilizing protection with a low-dose challenge compared to control levels. Protection was directly correlated with high-level antibody titers but not CD4+T cell responses. Finally, protective immunity was also induced using the Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE) as the adjuvant, which also correlated with high antibody titers yet CD4+T cell immunity that was significantly less potent than that with poly(I·C)LC. Overall, these data suggest that full-length CS proteins and poly(I·C)LC or GLA-SE offer a simple vaccine formulation to be used alone or in combination with other vaccines for preventing malaria infection. |
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