Use of Syntex Adjuvant Formulation to Augment Humoral Responses to Hepatitis B Virus Surface Antigen and to Influenza Virus Hemagglutinin

Abstract

The need for a safe, efficacious, widely applicable adjuvant formulation for use in vaccines has long been apparent. Living viruses can produce severe infections in persons with immunodeficiency, and possible undesirable long-term effects of viral nucleic acids are being recognized. For these reasons there is a trend towards use of subunit vaccines extracted from viruses or produced by recombinant DNA technology and synthetic antigens. Many of these antigens are relatively weak immunogens so the requirement for an effective formulation is even more critical. For some bacterial and viral diseases, humoral responses provide adequate protection. However, in the case of a number of viruses, parasites, fungi and tumors, cell-mediated immunity is the major protective mechanism of the host response. The only adjuvants currently approved in the United States for use in human vaccines are aluminium salts (alum). While these compounds often induce adequate antibody responses to antigens, they are ineffective with some antigens, e.g. influenza virus hemagglutinin: furthermore, alum does not consistently augment cell-mediated immune responses. Syntex adjuvant formulation (SAF) has been shown to be efficacious with several antigens in various animal species (Byars and Allison, 1987; Byars et al, 1989; Robey et al, 1986; Marx et al, 1986; Letvin et al, 1987). Both humoral and cell-mediated responses are increased when vaccines are formulated with SAF. To provide experimental evidence justifying the use of SAF in humans, our first objective was to show that the adjuvant formulation can increase the efficacy of established vaccines. A second goal is the use of SAF for novel vaccines.