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: C M Richards, A T Aman, T R Hirst, T J Hill, N A Williams
• Journal: Journal of virology (J Virol) Vol. 75 Issue 4 Pg. 1664-71 (Feb 2001) ISSN: 0022-538X [Print] United States
• PMID: 11160664 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Antibodies, Viral
• Bacterial Toxins
• Enterotoxins
• Escherichia coli Proteins
• Recombinant Proteins
• Viral Envelope Proteins
• Cholera Toxin
• heat-labile enterotoxin, E coli

Topics

• Adjuvants, Immunologic
• Administration, Intranasal
• Animals
• Antibodies, Viral (blood)
• Bacterial Toxins (genetics, immunology)
• Cholera Toxin (genetics, immunology)
• Enterotoxins (genetics, immunology)
• Escherichia coli (metabolism)
• Escherichia coli Proteins
• Female
• Herpesvirus 1, Human (immunology)
• Immunity, Mucosal
• Immunization
• Keratitis, Herpetic (immunology)
• Mice
• Recombinant Proteins (immunology)
• Viral Envelope Proteins (immunology)