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 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.
Sambhara
S
S
Department of Immunology, Research Center, Pasteur Mérieux Connaught Canada, Toronto.
Woods
S
S
Arpino
R
R
Kurichh
A
A
Tamane
A
A
Underdown
B
B
Klein
M
M
Lövgren Bengtsson
K
K
Morein
B
B
Burt
D
D
D000818:Animals; D003429:Cross Reactions; D004305:Dose-Response Relationship, Drug; D005260:Female; D016882:ISCOMs; D009980:Influenza A virus / Q000145:classification / Q000276:immunology; D007252:Influenza Vaccines; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors; D014771:Virion / Q000276:immunology
D016882:ISCOMs; D007252:Influenza Vaccines