Journal
VACCINE
Volume 26, Issue 48, Pages 6132-6142Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2008.08.070
Keywords
P vivax; Vaccine; Flagellin; FliC; TLR5; CpG ODN; TLR9
Categories
Funding
- Fundacao de Amparo A Pesquisa do Estado de Sao Paulo
- Fundacao de Amparo A Pesquisa do Estado do Rio de Janeiro
- The Millennium Institute for Vaccine Development and Technology [CNPq-420067/2005-1]
- DYB
- DSR
- CJMB
- BOC
- NME
- FAPESR
- FTMC
- AJV
- LCSF
- ISS
- MMR
- CNPq
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The present study evaluated the immunogenicity of new malaria vaccine formulations based on the 19 kDa C-terminal fragment of Plasmodium vivax Merozoite Surface Protein-1 (MSP1(19)) and the Salmonella enterica serovar Typhimurium flagellin (FIiC), a Toll-like receptor 5 (TLR5) agonist. FHC was used as an adjuvant either admixed or genetically linked to the P. vivax MSP1(19) and administered to C57BL/6 mice via parenteral (s.c.) or mucosal (i.n.) routes. The recombinant fusion protein preserved MSP1(19) epitopes recognized by Sera collected from P. vivax infected humans and TLR5 agonist activity. Mice parenterally immunized with recombinant P vivax MSPI 19 in the presence of FliC, either admixed or genetically linked, elicited strong and long-lasting MSP1 (19)-specific systemic antibody responses with a prevailing IgG1 subclass response. Incorporation of another TLR agonist, CpG ODN 1826, resulted in a more balanced response, as evaluated by the IgG1/IgG2c ratio, and higher cell-mediated immune response measured by interferon-gamma secretion. Finally, we show that MSPI 19-specific antibodies recognized the native protein expressed on the surface of P. vivax parasites harvested from infected humans. The present report proposes a new class of malaria vaccine formulation based on the use of malaria antigens and the innate immunity agonist FliC. it contains intrinsic adjuvant properties and enhanced ability to induce specific humoral and cellular immune responses when administered alone or in combination with other adjuvants. (C) 2008 Elsevier Ltd. All rights reserved.
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