Immunization against influenza by the ocular route

The immunogenicity of influenza A strain A/Northern Territory/60/68 for CSL mice when delivered by the ocular, nasal and subcutaneous routes was determined according to the median protective dose, PD50, i.e. the dose of infectious virus required to induce inhibition of multiplication of a standard intranasal challenge dose of 10(4.5) median tissue-culture-infectious doses (TCID50) of homologous virus three weeks after vaccination (PD50). For mice inoculated by the ocular route, an immunizing dose of 10(2.89) TCID50 per animal was required. For anaesthetized mice vaccinated intranasally and unanaesthetized mice vaccinated subcutaneously these figures are less than 10(2.00) and greater than 10(6.00) TCID50 per animal, respectively. The lower immunogenicity of virus delivered by the ocular route compared with the intranasal route can be correlated with a lowered capacity of ocularly administered virus to replicate in the murine respiratory tract. The immunogenicity of A/Ann Arbor/6/60-ca administered in two identical doses, was also determined for (a) the intraocular route, (b) the intranasal route with anaesthetized animals and (c) the intranasal route with unanaesthetized animals, using the parental A/Ann Arbor/6/60 as the challenge virus. Two doses were required because ca viruses have been shown to be poor immunogens in the same animal model. The PD50 for the ocular route was 10(2.83) TCID50 per animal compared with 10(2.71) for the intranasal route using unanaesthetized animals and 10(1.36) for the intranasal route using anaesthetized animals. Administration of living attenuated vaccine viruses by the ocular route is thus an effective means of inducing immunity to influenza viruses in the respiratory tract of mice.