Abstract
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.
Highlights
For immunization against influenza, there are two major routes of vaccination: muscular injection and intranasal (IN) administration
To evaluate the efficacy of various adjuvants in regards to whether they can enhance systemic and mucosal antibody production when used with protein antigen by eye-route vaccination, BALB/c mice were immunized with OVA (100 μg/head) protein plus several conventionally used adjuvants, including cholera toxin (CT) (2 μg/head), poly(I:C) (10 μg/head), MPLA (10 μg/head), or Imject Alum (1 mg/head), which is a commercially used alum adjuvant, three times at one-week intervals
To examine whether the Ab production-enhancing effect adjuvanted by CT or poly(I:C) was retained in influenza subunit-vaccine immunized mice, as shown in Fig 1A, BALB/c mice were immunized with 1 μg of the seasonal influenza vaccine, consisting of trivalent HAs of A/ New Caledonia/20/99 (H1N1), A/Panama/2007/97 (H3N2), and B/Shandong/7/97 influenza (B) viruses, with the same adjuvants that were previously used with OVA protein
Summary
There are two major routes of vaccination: muscular injection and intranasal (IN) administration. Intranasal administration induces both systemic IgG and mucosal secretory-IgA (S-IgA) production, initiating mucosal immunity; intranasal vaccination is more potent than parenteral injection for the prevention of influenza [1, 2]. LAIV can cause some side effects such as sore throat, coryza, and febrile reactions [3] As a result, it is not allowed for use in pregnant woman and immunodeficient patients, as well as in children under the age of 12 months [4] or adults over 50 [5]. Many studies have attempted to devise alternative ways of inducing mucosal immunity to circumvent the side effects of the intranasal influenza vaccines
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