Induction of Mucosal Immunity against Herpes Simplex Virus Type 1 in the Mouse Protects against Ocular Infection and Establishment of Latency

• Published in: The Journal of infectious diseases Vol. 177; no. 6; pp. 1451 - 1457
• Main Authors: Richards, C.M., Shimeld, C., Williams, N. A., Hill, T. J.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.06.1998; University of Chicago Press
• Subjects: Adjuvants, Immunologic - administration & dosage; Animals; Antibodies, Viral - blood; Antigens; Biological and medical sciences; Cercopithecus aethiops; Cholera Toxin - administration & dosage; Cytokines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Fundamental and applied biological sciences. Psychology; Glycoproteins; Herpesvirus 1, Human - immunology; Herpesvirus 1, Human - physiology; Human herpesvirus 1; Humans; Immunity, Mucosal; Immunization; Infections; Keratitis, Herpetic - immunology; Keratitis, Herpetic - prevention & control; Keratitis, Herpetic - virology; Lymph nodes; Major Articles; Male; Mice; Microbiology; Neutralization Tests; T lymphocytes; T-Lymphocytes - immunology; Tumor Cells, Cultured; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vero Cells; Viral Envelope Proteins - administration & dosage; Viral Envelope Proteins - immunology; Virology; Virus Latency; Viruses; Immunization; Herpesviridae; Alphaherpesvirinae; Rodentia; Vaccine; Intranasal administration; Latency; Virus; Vertebrata; Eye disease; Mammalia; Herpesvirus hominis 1; Mouse; Animal; T-Lymphocyte; Humoral immunity
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/515302

Immune responses were assessed after intranasal immunization of mice with a mixture of herpes simplex virus type 1 (HSV-1) glycoproteins with cholera toxin and its B subunit as adjuvant. Antigen-specific serum antibodies, which were largely IgG with IgG1 the major subclass, neutralized virus in vitro with a titer equivalent to that elicited by active infection. Significant levels of antigen-specific IgA were found in mucosal fluids of the eye as well as the vagina. Lymphocytes from draining lymph nodes showed secondary proliferative responses when cultured with HSV-1 in vitro, in immunized mice only, with the production of interleukin-2, interferon-γ, interleukin-4, and interleukin-5. After ocular challenge, immunized mice were protected against the development of severe eye disease, zosteriform spread, or encephalitis, whereas the incidence of clinical symptoms in mock-immunized mice was 83%, 74%, and 52%, respectively. Finally, the incidence of latency was reduced from 88% to 13% after intranasal immunization.