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

Abstract

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.

Large‐scale comparison of experimental adjuvants with herpes simplex virus vaccine reveals a correlation of protection with IgG2a and IgG2b responses

“…Mortality and weight loss in mice were only observed following administration of the ISCOM TM preparation and such effects have been described by others [Kersten et al, 1988;Pyle et al, 1989;Verheul et al, 1989;Leenaars et al, 1995;Stieneker et al, 1995;Coulter et al, 1998;Sambhara et al, 1998]. Although associated with the hemolytic properties of the Quil A component of the ISCOM TM preparation [Bangham and Horne, 1962], this toxicity is manifested only in mice, and both ISCOMs TM and free Quil A are well tolerated in other animal species including rats, guinea pigs and rabbits [Tschesche and Wulff, 1973;Trudel et al, 1987;Speijers et al, 1988;Ertü rk et al, 1991].…”

Pandemic Influenza Vaccines

“…Yet another group reported that a vaccinia virus vector which expressed a sequence of NP that induced a sturdy CD8 + T cell response in mice, including in their lungs, completely failed to induce protective immunity as assessed by peak viral loads, morbidity or mortality (Lawson et al 1994). Heterotypic T cell-mediated protection was also reported after immunization of mice with an adjuvanted influenza virus vaccine (Sambhara et al 1998) or with DNA vaccines expressing internal proteins of influenza virus (Saha et al 2006;Fu et al 1997). Another group reported that protection upon intranasal immunization with an adjuvanted nucleoprotein vaccine was mediated by T helper cells of the Th1 type rather than by CD8 + T cells (Tamura et al 1996).…”

Influenza virosomes supplemented with GPI-0100 adjuvant: a potent vaccine formulation for antigen dose sparing

“…In an attempt to further improve the immunogenicity of influenza vaccines we compared in this study the effects of GPI-0100 adjuvantion on a subunit and a virosomal influenza were required to provide complete lung protection against homologous challenge [27].…”