Safety and immunogenicity of INV21, an inactivated vaccine candidate for the prevention of hand, foot and mouth disease caused by enterovirus 71

Background: Hand foot and mouth disease (HFMD) is caused by enteroviral pathogens such as enterovirus 71 (EV71). Characteristically a self-limiting disease indicated by fever, mouth ulcers, and rash, HFMD caused by EV71 can lead to viral meningo-encephalitis, myocarditis or poliomyelitis-like paralysis, and may be fatal. EV71 and HFMD are endemic in Asia, causing significant morbidity, mortality and economic impact in recent years. INV21 is a purified, inactivated EV71, alum-formulated vaccine, developed to prevent HFMD caused by EV71. This study evaluated INV21 in a Phase I clinical trial in healthy adults. Methods: Thirty-six healthy males and females aged 21 to 45 years were enrolled into a randomised, double-blind, placebo-controlled study at the Investigational Medicine Unit, National University Hospital, Singapore. Subjects were enrolled to either Low Dose [12 on INV21 (0.6 μg EV71/dose); 6 on placebo] or High Dose [12 on INV21 (3 μg EV71/dose); 6 on placebo] group. Subjects received two injections (Day 0, Day 28) intramuscularly, and were followed for safety and immunogenicity assessments through Day 196. Results: Thirty-five/36 subjects completed the study through Day 56. Most common adverse events in INV21 and placebo subjects (cough: 5/36 subjects; rhinorrhea: 5/36 subjects; pyrexia: 4/36 subjects; influenza: 3/36 subjects) were mild and time-resolved. Minimal reactions were observed at the injection site, with similar profiles seen at both dose levels. Mild (Grade 1) pain, tenderness and pruritis were reported in 1 subject in each treatment group. Grade 1 erythema and induration were reported in 1 subject in High Dose group. No clinically significant changes in chemistry, haematology and urinalysis parameters were observed in either group. Highest EV71-neutralising antibody titres were detected 2 weeks post second dose (Day 42), with all subjects seroconverting (≥ 4-fold rise in titre compared to baseline) at this time point (Low Dose GMT = 323; High Dose GMT = 452). Conclusion: This trial demonstrated that INV21 is a safe and immunogenic vaccine candidate for the prevention of HFMD caused by EV71. Future clinical trials are needed to address the ongoing regional HFMD epidemic, and reduce mortality and morbidity.