Inactivated Eyedrop Influenza Vaccine Adjuvanted with Poly(I:C) Is Safe and Effective for Inducing Protective Systemic and Mucosal Immunity

• Published in: PloS one Vol. 10; no. 9; p. e0137608
• Main Authors: Kim, Eun-Do, Han, Soo Jung, Byun, Young-Ho, Yoon, Sang Chul, Choi, Kyoung Sub, Seong, Baik Lin, Seo, Kyoung Yul
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10-09-2015; Public Library of Science (PLoS)
• Subjects: Adjuvants; Adjuvants, Immunologic; Administration, Intranasal; Animals; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antibody Formation - immunology; Antigens; Antigens, Viral - immunology; Brain; Brain research; Cholera; Cholera toxin; Conjunctiva; Cytokines; Dendritic cells; Dose-Response Relationship, Immunologic; Drug delivery systems; Engineering schools; Eye; FDA approval; Female; Gene expression; Hemagglutinins; Homology; Hospitals; Humans; Immunity; Immunity, Mucosal; Immunization; Immunoglobulin A; Immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunoglobulins; Infections; Infiltration; Inflammation; Influenza; Influenza A; Influenza A Virus, H1N1 Subtype - immunology; Influenza vaccines; Influenza Vaccines - administration & dosage; Influenza Vaccines - adverse effects; Influenza Vaccines - immunology; Inoculation; Interleukin 6; Leukocytes (mononuclear); Medicine; Methods; Mice; Mucosal immunity; Mucous membrane; Olfactory bulb; Ophthalmic Solutions - administration & dosage; Ophthalmic Solutions - adverse effects; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Physiological aspects; Poly I-C; Polyinosinic:polycytidylic acid; Prevention; Public health; Rodents; Salmonella; Vaccination; Vaccines; Vaccines, Inactivated; Viral infections; Viruses; Water-borne diseases; Waterborne diseases; South Korea
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0137608

The eye route has been evaluated as an efficient vaccine delivery routes. However, in order to induce sufficient antibody production with inactivated vaccine, testing of the safety and efficacy of the use of inactivated antigen plus adjuvant is needed. Here, we assessed various types of adjuvants in eyedrop as an anti-influenza serum and mucosal Ab production-enhancer in BALB/c mice. Among the adjuvants, poly (I:C) showed as much enhancement in antigen-specific serum IgG and mucosal IgA antibody production as cholera toxin (CT) after vaccinations with trivalent hemagglutinin-subunits or split H1N1 vaccine antigen in mice. Vaccination with split H1N1 eyedrop vaccine antigen plus poly(I:C) showed a similar or slightly lower efficacy in inducing antibody production than intranasal vaccination; the eyedrop vaccine-induced immunity was enough to protect mice from lethal homologous influenza A/California/04/09 (H1N1) virus challenge. Additionally, ocular inoculation with poly(I:C) plus vaccine antigen generated no signs of inflammation within 24 hours: no increases in the mRNA expression levels of inflammatory cytokines nor in the infiltration of mononuclear cells to administration sites. In contrast, CT administration induced increased expression of IL-6 cytokine mRNA and mononuclear cell infiltration in the conjunctiva within 24 hours of vaccination. Moreover, inoculated visualizing materials by eyedrop did not contaminate the surface of the olfactory bulb in mice; meanwhile, intranasally administered materials defiled the surface of the brain. On the basis of these findings, we propose that the use of eyedrop inactivated influenza vaccine plus poly(I:C) is a safe and effective mucosal vaccine strategy for inducing protective anti-influenza immunity.