Vaccination against canine distemper virus infection in infant ferrets with and without maternal antibody protection, using recombinant attenuated poxvirus vaccines

Canine distemper virus (CDV) infection of ferrets is clinically and immunol ogically similar to measles, making this a useful model for the human disea se. The model was used to determine if parenteral or mucosal immunization o f infant ferrets at 3 and 6 weeks of age with attenuated vaccinia virus (NY VAC) or canarypox virus (ALVAC) vaccine strains expressing the CDV hemagglu tinin (H) and fusion (F) protein genes (NYVAC-HF and ALVAC-HF) would induce serum neutralizing antibody and protect against challenge infection at 12 weeks of age. Ferrets without maternal antibody that were vaccinated parent erally with NYVAC-HF (n = 5) or ALVAC-HF (n = 4) developed significant neut ralizing titers (log(10) inverse mean titer a standard deviation of 2.30 +/ - 0.12 and 2.20 +/- 0.34, respectively) by the day of challenge, and all su rvived with no clinical or virologic evidence of infection. Ferrets without maternal antibody that were vaccinated intranasally (i.n.) developed lower neutralizing titers, with NYVAC-HF producing higher titers at challenge (1 .11 +/- 0.57 versus 0.40 +/- 0.37, P = 0.02) and a better survival rate (6/ 7 versus 0/5, P = 0.008) than ALVAC-HF. Ferrets with maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 7) and ALVAC-HF (n = 7) de veloped significantly higher antibody titers (1.64 +/- 0.54 and 1.28 +/- 0. 40, respectively) than did ferrets immunized with an attenuated CDV vaccine (0.46 +/- 0.59; n = 7) or the recombinant vectors expressing rabies glycop rotein (RG) (0.19 +/- 0.32; n = 8, P = 7 x 10(-6)). The NYVAC vaccine also protected against weight loss, and both the NYVAC and attenuated CDV vaccin es protected against the development of some clinical signs of infection, a lthough survival in each of the three vaccine groups was low (one of seven) and not significantly different from the RG controls (none of eight). Comb ined i.n.-parenteral immunization of ferrets with maternal antibody using N YVAC-HF (n = 9) produced higher titers (1.63 +/- 0.25) than did i.n. immuni zation with NYVAC-HF (0.88 +/- 0.36; n = 9) and ALVAC-HF (0.61 +/- 0.43; n = 9, P = 3 x 10(-7)), and survival was also significantly better in the i.n .-parenteral group (3 of 9) than in the other HP-vaccinated animals (none o f 18) or in controls immunized with RG (none of 5) (P = 0.0374). Multiple r outes were not tested with the ALVAC vaccine. The results suggest that infa nt ferrets are less responsive to i.n, vaccination than are older ferrets a nd raises questions about the appropriateness of this route of immunization in infant ferrets or infants of other species.