Canine distemper virus (CDV)
infection of ferrets is clinically and immunologically similar to
measles, making this a useful model for the human disease. The model was used to determine if parenteral or mucosal immunization of infant ferrets at 3 and 6 weeks of age with attenuated vaccinia virus (NYVAC) or canarypox virus (
ALVAC) vaccine strains expressing the CDV
hemagglutinin (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 parenterally with NYVAC-HF (n = 5) or ALVAC-HF (n = 4) developed significant neutralizing titers (log(10) inverse mean titer +/- standard deviation of 2.30 +/- 0.12 and 2.20 +/- 0.34, respectively) by the day of challenge, and all survived 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) developed 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 glycoprotein (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
vaccines protected against the development of some clinical signs of
infection, although survival in each of the three
vaccine groups was low (one of seven) and not significantly different from the RG controls (none of eight). Combined i.n.-parenteral immunization of ferrets with maternal antibody using NYVAC-HF (n = 9) produced higher titers (1.63 +/- 0. 25) than did i.n. immunization 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 HF-vaccinated animals (none of 18) or in controls immunized with RG (none of 5) (P = 0.0374). Multiple routes were not tested with the
ALVAC vaccine. The results suggest that infant ferrets are less responsive to i.n. vaccination than are older ferrets and raises questions about the appropriateness of this route of immunization in infant ferrets or infants of other species.