Protective responses in mice to vaccination with multiply administered cold-adapted influenza vaccine reassortants and wild-type viruses

Abstract

Protective responses to influenza vaccine reassortants derived from the cold-adapted ( ca) donor strains A/Leningrad/134/17/57 and B/USSR/60/69 and wild-type epidemic viruses were studied in two strains of mice. Preliminary experiments revealed that, when mixtures of three viruses were inoculated intranasally to mice with 50 μl containing 10 6 EID 50 per 200 μl (10 5.4 EID 50 per mouse), interference between strains did not occur. However, interference with the growth of the influenza reassortant B/60/32/R took place if its concentration in the mixture was reduced to 10 5 (10 4.4 per mouse) or if it was inoculated at 10 6 EID 50 (10 5.4 per mouse) in the presence of the influenza reassortant R 34 and two other influenza A epidemic strains; interference was unrelated to serological responses to infection with B/60/32/R. Despite evidence of interference, mice inoculated with the same mixtures in two identical doses, three weeks apart, were able to clear a challenge from each of seven homotypic and heterotypic influenza A and B strains. Heterotypic clearance of influenza A challenge viruses was greater following mixed infection, indicating that common determinants within the surface antigen glycoproteins contributed to immune responses which were broader than could be expected to be induced by parenteral vaccination.