title: Protective mucosal immunity to ocular herpes simplex virus type 1 infection in mice by using Escherichia coli heat-labile enterotoxin B subunit as an adjuvant.
abstract: The potential of nontoxic recombinant B subunits of cholera toxin (rCtxB) and its close relative Escherichia coli heat-labile enterotoxin (rEtxB) to act as mucosal adjuvants for intranasal immunization with herpes simplex virus type 1 (HSV-1) glycoproteins was assessed. Doses of 10 microg of rEtxB or above with 10 microg of HSV-1 glycoproteins elicited high serum and mucosal anti-HSV-1 titers comparable with that obtained using CtxB (10 microg) with a trace (0.5 microg) of whole toxin (Ctx-CtxB). By contrast, doses of rCtxB up to 100 microg elicited only meager anti-HSV-1 responses. As for Ctx-CtxB, rEtxB resulted in a Th2-biased immune response with high immunoglobulin G1 (IgG1)/IgG2a antibody ratios and production of interleukin 4 (IL-4) and IL-10 as well as gamma interferon by proliferating T cells. The protective efficacy of the immune response induced using rEtxB as an adjuvant was assessed following ocular challenge of immunized and mock-immunized mice. Epithelial disease was observed in both groups, but the immunized mice recovered by day 6 whereas mock-immunized mice developed more severe corneal disease leading to stromal keratitis. In addition, a significant reduction in the incidence of lid disease and zosteriform spread was observed in immunized animals and there was no encephalitis compared with 95% encephalitis in mock-immunized mice. The potential of such mucosal adjuvants for use in human vaccines against pathogens such as HSV-1 is discussed.
authors.affiliation: Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom. Claire.M.Richards@bristol.ac.uk
authors.forename: C M
authors.initials: CM
authors.lastname: Richards
authors.forename: A T
authors.initials: AT
authors.lastname: Aman
authors.forename: T R
authors.initials: TR
authors.lastname: Hirst
authors.forename: T J
authors.initials: TJ
authors.lastname: Hill
authors.forename: N A
authors.initials: NA
authors.lastname: Williams
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D002772:Cholera Toxin / Q000235:genetics / Q000276:immunology*; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology*; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology*; D018928:Immunity, Mucosal; D007114:Immunization; D016849:Keratitis, Herpetic / Q000276:immunology*; D051379:Mice; D011994:Recombinant Proteins / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli