Immunogenicity of a thermally inactivated rotavirus vaccine in mice

Abstract

Current approaches to the prevention of severe rotavirus diarrhea and deaths in children have all been through the use of live oral vaccines. To develop a safe and effective inactivated rotavirus vaccine (IRV), a new simple, rapid and robust method for the inactivation is critical and essential because chemical inactivation commonly used for a number of killed vaccines has been a challenge and problematic for rotavirus. We have examined an array of thermal conditions and demonstrated that purified YK-1 rotavirus in diluent buffer can be completely inactivated by heat treatment, as evidenced by the lack of virus growth in 2 successive passages in cell culture. Unlike chemical treatment that often causes physical and biochemical damages to viruses, thermally inactivated rotavirus particles maintained their structural, biochemical and antigenic integrity. A two-dose intramuscular administration of thermally inactivated YK-1 rotavirus without adjuvant resulted in high titers of total and neutralizing antibody in serum of mice. Adjuvant Al(OH)3 further led to enhanced antibody titers and also dramatically lowered the amount of antigens in the vaccine formulation. Our results demonstrate the potential of heat inactivation as a novel approach to the manufacture of a safe and efficacious parenteral rotavirus vaccine, which should serve as an important addition to and back up for live oral rotavirus vaccine in children.