Systems Biology of Vaccination for EV71 Vaccine in Humans

Study Overview
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Brief Summary
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Recently, an inactivated vaccine (vero cell) against EV71 has been investigated in Phase 1 and Phase 2 clinical trials. Data from these trials showed that the EV71 vaccine has good safety profile and was immunogenic. 320 U alum-adjuvant vaccine has been chosen as the candidate vaccine for the phase 3 clinical trial. This clinical trial is a supplementary phase 2 trial, which is designed to study the gene expression patterns induced by EV71 vaccine in Chinese healthy children aged from 2 to 5 years old use a systems biology approach combined with microarray analysis，RT-PCR and neutralizing antibody testing for PBMC and serum collected form the studied children population, to predict immunogenicity, and explore mechanistic insights about the EV71 vaccine.

Official Title
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Systems Biology of Vaccination for EV71 Vaccine in Chinese Healthy Children Aged From 2 to 5 Years Old

Conditions
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Systems Biology, Early Gene, EV71 Vaccine

Intervention / Treatment
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* Biological: 320U /0.5ml
* Biological: 0/0.5ml placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects aged from 2 to 5 years old as established by medical history and clinical examination The pre-vaccination neutralizing antibody against EV71 <1:8 which is determined by ELISA The subjects' guardians are able to understand and sign the informed consent Had never received the vaccine against EV71 Subjects who can and will comply with the requirements of the protocol Subjects with temperature <37.1°C on axillary setting Exclusion Criteria: Subject who has a medical history of HFMD <= 37 weeks gestation Subjects with a birth weight <2.5 kg Subject that has a medical history of any of the following: allergic history, or allergic to any ingredient of vaccine Family history of seizures or progressive neurological disease Family history of congenital or hereditary immunodeficiency Severe malnutrition or dysgenopathy Major congenital defects or serious chronic illness, including perinatal brain damage Autoimmune disease Bleeding disorder diagnosed by a doctor or significant bruising or bleeding difficulties with IM injections or blood draws Any acute infections in last 7 days Any prior administration of immunodepressant or corticosteroids in last 6month Any prior administration of blood products in last 3 month Any prior administration of other research medicines in last 1month Any prior administration of attenuated live vaccine in last 28 days Any prior administration of inactivated vaccines in last 14 days, such as pneumococcal vaccine Under the anti - TB prevention or therapy Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 320U /0.5ml in children (from 2 to 5 years old)<br>inactivated vaccine(vero cell) against EV71 of 320U /0.5ml in 48 children aged 2-5 years old on day 0,28 | Biological: 320U /0.5ml<br>* inactivated vaccine(vero cell) against EV71 of 320U /0.5ml, two doses, 4 weeks interval<br>|
| Placebo Comparator: 0/0.5ml placebo in children (from 2 to 5 years old)<br>0/0.5ml placebo in 24 children aged 2-5 years old on day 0, 28 | Biological: 0/0.5ml placebo<br>* 0/0.5ml placebo, two doses, 4 weeks interval<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genomic signatures that predicted immune responses in infants vaccinated with EV71 vaccine | Identifying genomic signatures that predicted immune responses in infants vaccinated with EV71 vaccine at day 3 in children aged 2-5 years | Frame: 3 days after first dose | 
| Genomic signatures that predicted immune responses in infants vaccinated with EV71 vaccine | Identifying genomic signatures that predicted immune responses in infants vaccinated with EV71 vaccine at day 7 in children aged 2-5 years | 7 days after first dose | 
| Genomic signatures that predicted immune responses in infants vaccinated with EV71 vaccine | Identifying genomic signatures that predicted immune responses in infants vaccinated with EV71 vaccine at day 28 in children aged 2-5 years | 28 days after first dose | 
| Genomic signatures that predicted immune responses in infants vaccinated with EV71 vaccine | Identifying genomic signatures that predicted immune responses in infants vaccinated with EV71 vaccine at day 56 in children aged 2-5 years | 28 days after second dose | 
| Genomic signatures that predicted immune responses in infants vaccinated with EV71 vaccine | Identifying genomic signatures that predicted immune responses in infants vaccinated with EV71 vaccine at month 6 in children aged 2-5 years | 6 months after first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GMT, seroconversion rate of anti-EV71 antibodies in serum after first vaccination | GMT, seroconversion rate of anti-EV71 antibodies in serum 28 days after first vaccination | 28 days after the first vaccination | 
| GMT, seroconversion rate of anti-EV71 antibodies in serum after second vaccination | GMT, seroconversion rate of anti-EV71 antibodies in serum 28 days after second vaccination | 28 days after second vaccination | 
| the safety of EV71 vaccine in healthy children aged 2-5 years | Frequency of systemic and local adverse reactions within 28 days after the first dose of EV71 vaccine in healthy children aged 2-5 years | 28 days after the first dose | 
| the safety of EV71 vaccine in healthy children aged 2-5 years | Frequency of systemic and local adverse reactions within 28 days after the second dose of EV71 vaccine in healthy children aged 2-5 years | 28 days after the second dose |