HETEROTYPIC PROTECTION AGAINST INFLUENZA BY IMMUNOSTIMULATING COMPLEXES IS ASSOCIATED WITH THE INDUCTION OF CROSS-REACTIVE CYTOTOXIC T-LYMPHOCYTES

Influenza immunostimulating complexes (flu-ISCOMs) and a monovalent su bvirion vaccine prepared with an H1N1 strain of influenza virus were c ompared in mice for immunogenicity and protection against challenge wi th homologous and heterotypic influenza viruses. flu-ISCOMs but not su bvirion vaccine fully protected mice against homologous virus challeng e after one immunization as assessed by measurement of virus lung tite rs, 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 a nd reduced morbidity following challenge with an influenza virus of th e serologically distinct H2N2 subtype. This cross-protection correlate d with the induction of virus cross-reactive cytotoxic T lymphocytes t hat recognized a known major histocompatibility class I (H2-K-d)-restr icted epitope within the hemagglutinin of influenza virus that is cons erved among the H1 and H2 influenza virus subtypes. flu-ISCOMs may off er significant advantages over current commercial formulations as an i mproved influenza vaccine.