Journal Article

Heterotypic Protection against Influenza by Immunostimulating Complexes Is Associated with the Induction of Cross-Reactive Cytotoxic T Lymphocytes

Suryaprakash Sambhara, Samantha Woods, Rita Arpino, Anjna Kurichh, Alan Tamane, Brian Underdown, Michel Klein, Karin Lövgren Bengtsson, Bror Morein and David Burt

in The Journal of Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 177, issue 5, pages 1266-1274
Published in print May 1998 | ISSN: 0022-1899
Published online May 1998 | e-ISSN: 1537-6613 | DOI: http://dx.doi.org/10.1086/515285
Heterotypic Protection against Influenza by Immunostimulating Complexes Is Associated with the Induction of Cross-Reactive Cytotoxic T Lymphocytes

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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.

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Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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