Inactivated Eyedrop Influenza Vaccine Adjuvanted with Poly(I:C) Is Safe and Effective for Inducing Protective Systemic and Mucosal Immunity.
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.
Department of Ophthalmology, Eye and Ear Hospital, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Korea 21 Project for Medical Science, Yonsei University, Seoul, Republic of Korea.
Eun-Do
ED
Kim
Department of Ophthalmology, Eye and Ear Hospital, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
Soo Jung
SJ
Han
Department of Biotechnology, College of Engineering, Yonsei University, Seoul, Republic of Korea; Vaccine Translational Research Center, Yonsei University, Seoul, Republic of Korea.
Young-Ho
YH
Byun
Department of Ophthalmology, Eye and Ear Hospital, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
Sang Chul
SC
Yoon
The Graduate School of Yonsei University, Seoul, Republic of Korea; Department of Ophthalmology, National Health Insurance Corporation Ilsan Hospital, Gyounggi-do, Republic of Korea.
Kyoung Sub
KS
Choi
Department of Biotechnology, College of Engineering, Yonsei University, Seoul, Republic of Korea; Vaccine Translational Research Center, Yonsei University, Seoul, Republic of Korea.
Baik Lin
BL
Seong
Department of Ophthalmology, Eye and Ear Hospital, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
Kyoung Yul
KY
Seo
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007109:Immunity; D018928:Immunity, Mucosal; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D051379:Mice; D009883:Ophthalmic Solutions / Q000008:administration & dosage* / Q000009:adverse effects; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D011070:Poly I-C; D015164:Vaccines, Inactivated
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D009883:Ophthalmic Solutions; D015164:Vaccines, Inactivated; D011070:Poly I-C