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Immunogenicity of recombinant proteins consisting of Plasmodium vivax circumsporozoite protein allelic variant-derived epitopes fused with Salmonella enterica Serovar Typhimurium flagellin.
- Source :
-
Clinical and vaccine immunology : CVI [Clin Vaccine Immunol] 2013 Sep; Vol. 20 (9), pp. 1418-25. Date of Electronic Publication: 2013 Jul 17. - Publication Year :
- 2013
-
Abstract
- A Plasmodium falciparum circumsporozoite protein (CSP)-based recombinant fusion vaccine is the first malaria vaccine to reach phase III clinical trials. Resistance to infection correlated with the production of antibodies to the immunodominant central repeat region of the CSP. In contrast to P. falciparum, vaccine development against the CSP of Plasmodium vivax malaria is far behind. Based on this gap in our knowledge, we generated a recombinant chimeric protein containing the immunodominant central repeat regions of the P. vivax CSP fused to Salmonella enterica serovar Typhimurium-derived flagellin (FliC) to activate the innate immune system. The recombinant proteins that were generated contained repeat regions derived from each of the 3 different allelic variants of the P. vivax CSP or a fusion of regions derived from each of the 3 allelic forms. Mice were subcutaneously immunized with the fusion proteins alone or in combination with the Toll-like receptor 3 (TLR-3) agonist poly(I·C), and the anti-CSP serum IgG response was measured. Immunization with a mixture of the 3 recombinant proteins, each containing immunodominant epitopes derived from a single allelic variant, rather than a single recombinant protein carrying a fusion of regions derived from each of 3 allelic forms elicited a stronger immune response. This response was independent of TLR-4 but required TLR-5/MyD88 activation. Antibody titers significantly increased when poly(I·C) was used as an adjuvant with a mixture of the 3 recombinant proteins. These recombinant fusion proteins are novel candidates for the development of an effective malaria vaccine against P. vivax.
- Subjects :
- Adjuvants, Immunologic administration & dosage
Adjuvants, Immunologic genetics
Animals
Antibodies, Protozoan blood
Epitopes genetics
Epitopes immunology
Female
Flagellin genetics
Injections, Subcutaneous
Malaria Vaccines genetics
Mice
Plasmodium vivax genetics
Poly I-C administration & dosage
Poly I-C pharmacology
Protozoan Proteins genetics
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins immunology
Salmonella typhimurium genetics
Vaccines, Synthetic administration & dosage
Vaccines, Synthetic genetics
Vaccines, Synthetic immunology
Adjuvants, Immunologic pharmacology
Flagellin pharmacology
Malaria Vaccines administration & dosage
Malaria Vaccines immunology
Plasmodium vivax immunology
Protozoan Proteins immunology
Salmonella typhimurium immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1556-679X
- Volume :
- 20
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Clinical and vaccine immunology : CVI
- Publication Type :
- Academic Journal
- Accession number :
- 23863502
- Full Text :
- https://doi.org/10.1128/CVI.00312-13