Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2.

Abstract

The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG(1) and IgG(3) from putatively resistant individuals resident in S. mansoni endemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubility enhancing fusion partner. We also expressed in E. coli a chimera called Sm-TSP-2/5B, which consisted of Sm-TSP-2 fused to the immunogenic 5B region of the hookworm aspartic protease and vaccine antigen, Na-APR-1. Sm-TSP-2 formulated with alum/CpG showed significant reductions in adult worm and liver egg burdens in two separate murine schistosomiasis challenge studies. Sm-TSP-2/5B afforded significantly greater protection than Sm-TSP-2 alone when both antigens were formulated with alum/CpG. The enhanced protection obtained with the chimeric fusion protein was associated with increased production of anti-Sm-TSP-2 antibodies and IL-4, IL-10 and IFN-γ from spleen cells of vaccinated animals. Sera from 666 individuals from Brazil who were infected with S. mansoni were screened for potentially deleterious IgE responses to Sm-TSP-2. Anti-Sm-TSP-2 IgE to this protein was not detected (also shown previously for Na-APR-1), suggesting that the chimeric antigen Sm-TSP-2/5B could be used to safely and effectively vaccinate people in areas where schistosomes and hookworms are endemic.

• Authors: Mark S Pearson, Darren A Pickering, Henry J McSorley, Jeffrey M Bethony, Leon Tribolet, Annette M Dougall, Peter J Hotez, Alex Loukas
• Journal: PLoS neglected tropical diseases (PLoS Negl Trop Dis) Vol. 6 Issue 3 Pg. e1564 ( 2012) ISSN: 1935-2735 [Electronic] United States
• PMID: 22428079 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Alum Compounds
• Antibodies, Helminth
• Antigens, Helminth
• CPG-oligonucleotide
• Cytokines
• Immunoglobulin G
• Oligodeoxyribonucleotides
• Recombinant Fusion Proteins
• Tetraspanins
• Vaccines, Synthetic
• aluminum sulfate
• Aspartic Acid Proteases

Topics

• Adjuvants, Immunologic (administration & dosage)
• Adolescent
• Adult
• Aged
• Alum Compounds (administration & dosage)
• Animals
• Antibodies, Helminth (blood)
• Antigens, Helminth (administration & dosage, genetics, immunology)
• Aspartic Acid Proteases (administration & dosage, genetics, immunology)
• Brazil
• Child
• Child, Preschool
• Cytokines (metabolism)
• Disease Models, Animal
• Escherichia coli (genetics)
• Female
• Gene Expression
• Humans
• Immunoglobulin G (blood)
• Infant
• Leukocytes, Mononuclear (immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Middle Aged
• Oligodeoxyribonucleotides (administration & dosage)
• Recombinant Fusion Proteins (administration & dosage, genetics, immunology)
• Schistosomiasis (immunology, prevention & control)
• Spleen (immunology)
• Tetraspanins (administration & dosage, genetics, immunology)
• Vaccines, Synthetic (administration & dosage, immunology)
• Young Adult