A single oral dose of inactivated rotavirus and ISCOM matrices induces partial protection in lambs.

Rotavirus is a major cause of diarrhoea1 disease in young children and animals. Worldwide, it is responsible for 870,000 human deaths per year, primarily in the developing countries and causes significant economic losses in agriculture [ I ,2]. Natural infections in infancy prevent severe diarrhoea when subsequently challenged [3]. The current goal of rotavirus vaccination is to induce immunity which is at least as efficient as that elicited by natural infections [4]. To date all candidate rotavirus vaccines have failed in one or more aspects relating to safety, immunogenicity, or efficacy [ 1,2]. Vaccine development is preceding detailed characterisation of the mucosal humoral and cellular immune responses to rotavirus. Antibodies at the intestinal mucosa rather than in circulation are a prime protective factor and can mediate passive protection [ 5 ] . However, other protective immune mechanisms may be involved also and both cytotoxic lymphocytes and T helper cells have been demonstrated [6,7]. The aim of these experiments was to induce mucosal priming which would result in protection against subsequent challenge with rotavirus and to characterise the kinetics of both humoral and cellular aspects of this response. Since rotaviruses are ubiquitous, gnotobiotic lambs were used as a model for mucosal priming of immunologically naive subjects. Immune stimulating complexes or ISCOMs have been demonstrated as potent and effective antigen delivery systems for mucosal immunisation and were used in this study as an adjuvant for inactivated rotavirus [8].