Influenza immunostimulating complexes (flu-ISCOMs) and a monovalent subvirion vaccine prepared with an H1N1 strain of influenza virus were compared in mice for immunogenicity and protection against challenge with homologous and heterotypic influenza viruses. flu-ISCOMs but not subvirion vaccine fully protected mice against homologous virus challenge after one immunization as assessed by measurement of virus lung titers. The improved protection induced by flu-ISCOMs was associated with a 10-fold higher prechallenge serum hemagglutination inhibition titer. Furthermore, only flu-ISCOMs fully protected mice against mortality and reduced morbidity following challenge with an influenza virus of the serologically distinct H2N2 subtype. This cross-protection correlated with the induction of virus cross-reactive cytotoxic T lymphocytes that recognized a known major histocompatibility class I (H2-Kd)-restricted epitope within the hemagglutinin of influenza virus that is conserved among the H1 and H2 influenza virus subtypes. flu-ISCOMs may offer significant advantages over current commercial formulations as an improved influenza vaccine.
Two commercial live virus infectious bovine rhinotracheitis (IBR) vaccines for intranasal administration and an inactivated polyvalent calf pneumonia vaccine were compared for safety and efficacy in calves against experimental IBR infections. All three products were clinically safe for use in young calves; a mild, transient, febrile response was induced by one of the live vaccines. Vaccinal virus was recovered for up to 16 days after vaccination from nasal secretions of all calves given live vaccine. Both live vaccines stimulated a serum neutralising antibody response, but the inactivated vaccine failed to elicit any serological response. Following intranasal challenge four months after the first dose of vaccine, all live virus vaccinates remained systemically healthy. A slight nasal discharge and a few rapidly healing ulcers of the nasal mucosa were the only abnormalities observed. Both the group given the inactivated vaccine and the unvaccinated controls developed clinical IBR with pyrexia, ocular and nasal discharges, severe ulceration of the nasal mucosa and tracheitis and tachypnoea to varying degrees of severity. Parenteral administration of dexamethasone six months after challenge induced reactivation of virus shedding followed by a rise in humoral antibody titre irrespective of the original vaccination history.
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