An inactivated enterovirus 71 vaccine is safe and immunogenic in healthy adults: A phase I,double blind,randomized, placebo-controlled,study of two dosages |
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Institution: | 1. Department of Medicine, NUH Investigational Medicine Unit, Yong Loo Lin School of Medicine, National University of Singapore, 1E, Kent Ridge Road, NUHS Tower Block, Level 10, Singapore 119228, Singapore;2. Vaccine Business Unit, Takeda Pharmaceuticals Asia Pacific Pte Ltd, 21 Biopolis Road, Nucleos South Tower Level 4, Singapore 138567, Singapore;3. Takeda Vaccines, Inc., Takeda Pharmaceuticals USA, Fort Collins, CO, USA;4. Vaccine Business Unit, Takeda Pharmaceuticals USA, 40 Landsdowne Street, Cambridge, MA 02139, USA |
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Abstract: | BackgroundHand, foot and mouth disease (HFMD), especially that caused by enterovirus 71 (EV71) infection, is a public health concern in the Asia-Pacific region. We report a phase I clinical trial of an EV71 candidate vaccine (INV21) based on a binary ethylenimine inactivated B2 sub-genotype formulated with aluminum hydroxide.MethodsIn this double-blind, placebo-controlled, randomized, dose escalation study adult volunteers received two vaccinations 28 days apart of low or high dose formulations of the candidate vaccine and were then monitored for safety and reactogenicity for four weeks after each dose, and for their immune responses up to 28 weeks.ResultsOf 36 adults enrolled, 35 completed the study as planned. Either no or mild adverse events were observed, mainly injection site pain and tiredness. Seroconversion was 100% after two vaccinations. High geometric mean neutralizing antibody titers (GMT) were observed 14 days post first dose, peaking 14 days post second dose (at Day 42) in both high and low dose groups; GMTs on days 14, 28, 42, and 56 were 128, 81, 323, 203 and 144, 100, 451, 351 in low- and high-dose groups, respectively. Titers for both doses declined gradually to Day 196 but remained higher than baseline and the placebo groups, which had low GMTs throughout the duration of the study. Cross-neutralizing antibody activity against heterologous sub-genotypes was demonstrated.ConclusionThese data show that the EV71 candidate vaccine is safe and immunogenic in adults and supports further clinical development as a potential pediatric vaccine by initiating a dose-escalation study for determining the dose-dependent safety and immunogenicity of the vaccine in young naïve children. |
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Keywords: | Enterovirus 71 vaccine B2 sub-genotype Phase I clinical trial Immunogenicity Seroconversion Cross-neutralization |
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