Oral immunization with a shiga toxin B subunit:: rotavirus NSP490 fusion protein protects mice against gastroenteritis

NW Choi, MK Estes, WHR Langridge - Vaccine, 2005 - Elsevier
NW Choi, MK Estes, WHR Langridge
Vaccine, 2005Elsevier
A fusion protein containing the shiga toxin-1 B subunit (STB) linked to a 90 amino acid
peptide (aa residues 86–175) from simian rotavirus (SA-11) nonstructural protein NSP4 was
synthesized in Escherichia coli. Mice orally inoculated with 60μg of STB:: NSP490 fusion
protein per dose generated higher humoral and intestinal antibody titers than mice
inoculated with 30μg of NSP4 alone. Serum anti-NSP4 IgG2a isotype titers were
substantially greater than IgG1 titers, suggesting a dominant Th1 immune response. ELISA …
A fusion protein containing the shiga toxin-1 B subunit (STB) linked to a 90 amino acid peptide (aa residues 86–175) from simian rotavirus (SA-11) nonstructural protein NSP4 was synthesized in Escherichia coli. Mice orally inoculated with 60μg of STB::NSP490 fusion protein per dose generated higher humoral and intestinal antibody titers than mice inoculated with 30μg of NSP4 alone. Serum anti-NSP4 IgG2a isotype titers were substantially greater than IgG1 titers, suggesting a dominant Th1 immune response. ELISA measurement of cytokines secreted from splenocytes isolated from immunized mice confirmed the STB::NSP490 fusion protein stimulation of a strong Th1 cell mediated immune response. Diarrhea in SA-11 rotavirus challenged neonates suckling from STB::NSP4 immunized dams was significantly reduced in severity and duration in comparison with virus challenged neonates from unimmunized mice. Together, our experiments demonstrate for the first time that the shiga toxin B subunit provides ligand mediated delivery of virus antigens to the gut-associated lymphoid tissues for enhanced stimulation of humoral and cellular responses against rotavirus gastroenteritis.
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