Preclinical Evaluation of the Immunogenicity and Safety of an Inactivated Enterovirus 71 Candidate Vaccine

Abstract

Human enterovirus 71 (EV71) is a significant cause of morbidity and mortality from Hand, Foot and Mouth Disease (HFMD) and neurological complications, particularly in young children in the Asia-Pacific region. There are no vaccines or antiviral therapies currently available for prevention or treatment of HFMD caused by EV71. Therefore, the development of therapeutic and preventive strategies against HFMD is of growing importance. We report the immunogenic and safety profile of inactivated, purified EV71 preparations formulated with aluminum hydroxide adjuvant in preclinical studies in mice and rabbits. In mice, the candidate vaccine formulations elicited high neutralizing antibody responses. A toxicology study of the vaccine formulations planned for human use performed in rabbits showed no vaccine-related pathological changes and all animals remained healthy. Based on these preclinical studies, Phase 1 clinical testing of the EV71 inactivated vaccine was initiated. Enterovirus 71 (EV71) is one of the major viruses causing Hand, Foot, and Mouth Disease, a highly contagious illness which primarily affects young children in the Asia-Pacific region and can sometimes be fatal. No vaccines or antivirals for Hand, Foot, and Mouth Disease are available at this time. We developed an experimental vaccine using inactivated, purified EV71 with an adjuvant to amplify the immune response. When this vaccine was tested in mice and rabbits, they produced large amounts of antibodies that could neutralize the virus. We were reasonably certain that the vaccine would be safe because rabbits given repeated high doses did not develop pathological lesions or clinical symptoms. Based on these results, we proceeded to test the safety of the vaccine in human adults.