New malaria vaccine candidates based on thePlasmodium vivaxMerozoite Surface Protein-1 and the TLR-5 agonistSalmonellaTyphimurium FliC flagellin

• Published in: Vaccine Vol. 26; no. 48; p. 6132
• Main Authors: Bargieri, Daniel Y, Rosa, Daniela S, Braga, Catarina JM, Carvalho, Bruna O, Costa, Fabio TM, Espíndola, Noeli Maria, Vaz, Adelaide José, Soares, Irene S, Ferreira, Luis CS, Rodrigues, Mauricio M
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Limited 11-11-2008
• Subjects: Immune response; Immunization; Immunogenicity; Malaria; Medical research; Rodents; Salmonella; Vaccines; Vector-borne diseases
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2008.08.070

The present study evaluated the immunogenicity of new malaria vaccine formulations based on the 19kDa C-terminal fragment ofPlasmodium vivaxMerozoite Surface Protein-1 (MSP119) and theSalmonella entericaserovar Typhimurium flagellin (FliC), a Toll-like receptor 5 (TLR5) agonist. FliC was used as an adjuvant either admixed or genetically linked to theP. vivaxMSP119and administered to C57BL/6 mice via parenteral (s.c.) or mucosal (i.n.) routes. The recombinant fusion protein preserved MSP119epitopes recognized by sera collected fromP. vivaxinfected humans and TLR5 agonist activity. Mice parenterally immunized with recombinantP. vivaxMSP119in the presence of FliC, either admixed or genetically linked, elicited strong and long-lasting MSP119-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-γ secretion. Finally, we show that MSP119-specific antibodies recognized the native protein expressed on the surface ofP. vivaxparasites harvested from infected humans. The present report proposes a new class of malaria vaccine formulation based on the use of malarial 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.