S. Sambhara et al., HETEROTYPIC PROTECTION AGAINST INFLUENZA BY IMMUNOSTIMULATING COMPLEXES IS ASSOCIATED WITH THE INDUCTION OF CROSS-REACTIVE CYTOTOXIC T-LYMPHOCYTES, The Journal of infectious diseases, 177(5), 1998, pp. 1266-1274
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.