Enterovirus 71 ( EV71 ) outbreaks are a socioeconomic burden, especially in the western Pacific region. Results of phase 1 clinical trials suggest an EV71 vaccine has a clinically acceptable safety profile and immunogenicity.
A study has assessed the best possible dose and formulation, immunogenicity, and safety profile of this EV71 vaccine in healthy Chinese children.
This randomised, double-blind, placebo-controlled, phase 2 trial was undertaken at one site in Donghai County, Jiangsu Province, China.
Eligible participants were healthy boys or girls aged 6-36 months. Participants were randomly assigned ( 1:1:1:1:1 ) to receive either 160 U, 320 U, or 640 U alum-adjuvant EV71 vaccine, 640 U adjuvant-free EV71 vaccine, or a placebo ( containing alum adjuvant only ).
Participants and investigators were masked to the assignment.
The primary endpoint was anti-EV71 neutralising antibody geometric mean titres ( GMTs ) at day 56, analysed according to protocol.
Researchers have randomly assigned 1200 participants, 240 ( 120 aged 6-11 months [ infants ] and 120 aged 12-36 months [ children ] ) of whom were assigned to each dose.
1106 participants completed the study and were included in the according-to-protocol analysis.
The main reasons for dropout were withdrawal of consent and refusal to donate a blood sample. Infants who received the 640 U adjuvant vaccine had the highest GMTs on day 56 ( 742.2 ), followed by those who received the 320 U formulation ( 497.9 ).
For children, those who received the 320 U formulation had the highest GMTs on day 56 ( 1383.2 ).
Participants who received the vaccine had significantly higher GMTs than did who received placebo ( p less than 0.0001 ).
For the subgroup of participants who were seronegative at baseline, both infants and children who received the 640 U adjuvant vaccine had the highest GMTs on day 56 ( 522.8 in infants and 708.4 in children ), followed by those who received the 320 U adjuvant vaccine ( 358.2 in infants and 498.0 in children ).
549 ( 45.8% ) of 1200 participants reported at least one injection-site or systemic adverse reaction, but the incidence of adverse reactions did not differ significantly between groups ( p=0•36 ).
The 640 U alum-adjuvant vaccine group had a significantly higher incidence of induration than did the 640 U adjuvant-free group ( p=0•001 ).
Taking immunogenicity, safety, and production capacity into account, the 320 U alum-adjuvant formulation of the EV71 vaccine is probably the best possible formulation for phase 3 trials. ( Xagena )
Zhu F-C et al, The Lancet 2013; 381: 1037-1045