Development of an Influenza-Iscom™ Vaccine

Abstract

Annual immunisation of the elderly with trivalent influenza vaccines is an important public health measure (Mullooly et al, 1994). The efficacy of currently available vaccines ranges from 60 to 80% in young healthy adults, but is usually lower in the elderly (Fedson et al, 1993; Govaert et al. 1994). Vaccine uptake is less than optimal (CDC 1995; Nguyen-Van-Tarn and Nicholson, 1993) especially in this target group. Various ways have been investigated to increase vaccine efficacy including the use of adjuvants (Salk et al. 1952; Salk et al. 1953; Davenport et al. 1968; Glück et al. 1994; Martin, 1996), increased antigen dose (Arden et al. 1986; Palache et al. 1993), use of cell-culture rather than egg-grown viral antigen (Cox et al. 1995; Burnet, 1935) and temperature-sensitive (Subbarao et al. 1995) and cold-adapted (Khan et al. 1996) live virus vaccines. Of these approaches, adjuvants have been the only one to show increased protective efficacy, the most outstanding being the water-in-oil formulations of Salk et al. (1951), which clearly established the feasibility of this approach even though the reactivity of these vaccines was considered unacceptable (Beebe et al. 1964). This paper will describe our rationale for the choice of certain adjuvants with the potential to improve the efficacy of a human influenza vaccine, then give an overview of the initial evaluative studies in mice, and the optimisation steps for Immunostimulating Complexes (Iscom™ and Iscomatrix™, Iscotec AB, Sweden), our chosen adjuvant formulations for progress into clinical trial.