PROTECTIVE RESPONSES IN MICE TO VACCINATION WITH MULTIPLY ADMINISTERED COLD-ADAPTED INFLUENZA VACCINE REASSORTANTS AND WILD-TYPE VIRUSES

Protective responses to influenza vaccine reassortants derived from th e 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 mu l containing 10(6) EI D50 per 200 mu l (10(5.4) EID50 per mouse), interference between strai ns did not occur. However, interference with the growth of the influen za reassortant B/60/32/R took place if its concentration in the mixtur e was reduced to 10(5) (10(4.4) per mouse) or if it was inoculated at 10(6) EID50 (10(5.4) per mouse) in the presence of the influenza reass ortant R/34 and two other influenza A epidemic strains, interference w as unrelated to serological responses to infection with B/60/32/R. Des pite evidence of interference, mice inoculated with the same mixtures in two identical doses, three weeks apart, were able to clear a challe nge front each of seven homotypic and heterotypic influenza A and B st rains. Heterotypic clearance of influenza A challenge viruses was grea ter following mixed infection, indicating that common determinants wit hin the surface antigen glycoproteins contributed to immune responses which were broader than could be expected to be induced by parenteral vaccination. (C) 1997 Elsevier Science Ltd.