Abstract
We investigated eyedrop vaccination (EDV) in pre-clinical development for immunological protection against influenza and for potential side effects involving ocular inflammation and the central nervous system (CNS). Live attenuated influenza EDV, CA07 (H1N1), PZ-4 (H1N2) and Uruguay (H3N2), induced both systemic and mucosal virus-specific antibody responses in ferrets. In addition, EDV resulted in a clinically significant protection against viral challenge, and suppression of viral replication in nasal secretion and lung tissue. Regarding safety, we found that administered EDV flow through the tear duct to reach the base of nasal cavity, and thus do not contact the olfactory bulb. All analyses for potential adverse effects due to EDV, including histological and functional examinations, did not reveal significant side effects. On the basis of these findings, we propose that EDV as effective, while being a safe administration route with minimum local side effects, CNS invasion, or visual function disturbance.
Highlights
Mucosal vaccines have considerable advantages over those delivered through parenteral routes, since they can induce both systemic and mucosal antigen-specific immune responses and can be administered [1]
Intranasal spray is considered as a new therapeutic approach for central nervous system (CNS) disorders because it can cross the blood-brain barrier [5,6,7]; this serve as a serious limitation for vaccination purposes due to the possibility of adverse neurological side effects
Serum and nasal lavage samples were collected after each immunization to assess anti-Live-Attenuated Influenza Vaccine (LAIV) Hemagglutination inhibition (HI) titer levels
Summary
Mucosal vaccines have considerable advantages over those delivered through parenteral routes, since they can induce both systemic and mucosal antigen-specific immune responses and can be administered [1]. These immunizations are often administered via oral or intranasal routes, as exemplified with the oral polio vaccine (OPV) and recently approved FluMist influenza vaccine, respectively [2]. A recent investigation in mice determined that animals immunized with an influenza eyedrop vaccine (EDV) were protected from lethal pathogen infection [13]. The clinical significance of these results is inherently compromised since mice are not natural hosts of influenza
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