Tolerability, Safety, and Immunogenicity of Tetravalent Inactivated Enterovirus Vaccine (Vero Cell).

Overview

The trial aims to assess the tolerability, safety, and immunogenicity of the tetravalent inactivated enterovirus vaccine in adults and children aged 6 months to 12 years. The main questions it aims to answer are: * Phase Ⅰ: The safety of the investigational vaccine in the target population based on adverse events (AEs); * Phase Ⅱ: The immunogenicity of the investigational vaccine in the target population. In Phase I, researchers will compare the safety of the investigational vaccine at low, medium, and high doses with the control vaccine; in Phase II, they will compare the safety and immunogenicity (including immune persistence) of the investigational vaccine at medium and high doses with the control vaccine. Procedure: * In Phase I, will be vaccinated with the investigational vaccine (at low, medium, and high doses) or the control EV71 vaccine/placebo in a 3:1 ratio, following a vaccination schedule of 0 and 1 month. Within each age group, and under the premise of ensuring safety, a dose-escalation trial will be conducted in reverse order of age. * In Phase II, participants in each age group will be randomly assigned to the medium-dose, high-dose investigational vaccine groups, and the control group in a 1:1:1 ratio, receiving two doses of the investigational vaccine or the EV71 vaccine (for ages 6-71 months)/placebo (for ages 6-12 years), with a one-month interval between the two doses. * For all participants in both Phase I and Phase II, immediate reactions within 30 minutes after each dose will be observed. Diary cards/contact cards will be used to collect solicited local and systemic adverse events (AEs) for 0-7 days and unsolicited AEs for 0-30 days after vaccination. Additionally, serious adverse events (SAEs) will be monitored from the start of vaccination until 6 months post-completion of the vaccination schedule. Furthermore, for participants of reproductive age in Phase I, pregnancy events will be collected.

Both Phase I and Phase II clinical trials adopt a randomized, double-blind, controlled design. For Phase I, 192 healthy participants are planned to be enrolled, including 48 adults aged 18-59, 48 children aged 6-12, 48 children aged 24-71 months, and 48 children aged 6-23 months. They will receive two doses of the experimental vaccine or EV71 vaccine (for those aged 6-71 months) / placebo (for those aged 6-12 and 18-59) in the order of low-dose, medium-dose, and high-dose. The interval between the two doses is one month. Enrollment will follow the sequence of adults aged 18-59, children aged 6-12, children aged 24-71 months, and children aged 6-23 months. Within each dosage stage, there will be 16 participants from each age group, and they will receive the experimental vaccine or control EV71 vaccine / placebo in a 3:1 ratio. The dose escalation principle within each age group is low-dose, medium-dose, and high-dose. Based on the occurrence of AEs and clinical laboratory indicators, the next higher dose stage can only be initiated after a 0-7 day safety observation period following the first dose of the lower dose stage and confirmation of safety. The sequential enrollment principle across age groups is adults aged 18-59, children aged 6-12, children aged 24-71 months, and children aged 6-23 months. For each dose, after completing the 0-7 day safety observation period following the first dose and confirming safety, the next age group can proceed with enrollment for that dose. For adults aged 18-59 and children aged 6-12, venous blood and urine samples will be collected before each dose and on the 3rd day after vaccination for blood routine tests (about 2.0 ml of venous blood), blood biochemistry tests (about 2.0-3.0 ml of venous blood), and urine routine tests (about 2.0-10.0 ml of urine) to evaluate vaccine safety. For children aged 24-71 months, only about 2.0-3.0 ml of venous blood will be collected at the corresponding time points for blood biochemistry tests. If more than 10% of participants in each dose stage of the 24-71 month age group experience abnormal laboratory test results related to the investigational vaccine and of clinical significance after the first dose, then for the corresponding dose stage in the 6-23 month age group, blood routine tests (about 1.0 ml of venous blood), blood biochemistry tests (about 2.0-3.0 ml of venous blood), and urine routine tests (about 2.0-10.0 ml of urine) will be conducted on the 3rd day after the first dose, before the second dose, and on the 3rd day after the second dose. After obtaining safety data for all participants in Phase I for 30 days after the completion of vaccination, the data will be analyzed, and a safety analysis report will be submitted to the Data Monitoring Committee (DMC) and Ethical Committee (EC) for review. Only after confirming safety can the Phase II clinical trial be initiated. For Phase II, 360 healthy participants aged 6 months to 12 years are planned to be enrolled, including 120 children aged 6-23 months, 120 children aged 24-71 months, and 120 children aged 6-12. Participants in each age group will be randomly assigned to the medium-dose and high-dose groups of the investigational vaccine and the control group in a 1:1:1 ratio, receiving two doses of the investigational vaccine or EV71 vaccine (for those aged 6-71 months) / placebo (for those aged 6-12) with a one-month interval. With the day of the first dose as Day 0, all participants in Phase II will have about 3.0 ml of venous blood collected on Days 0, 60, and 210 to separate serum for EV71, CA16, CA10, and CA6 neutralizing antibody tests, evaluating the vaccine's immunogenicity and immune persistence. All participants in both Phase I and Phase II will be observed for immediate reactions within 30 minutes after each dose, and solicited local and systemic AEs will be collected for 0-7 days, while unsolicited AEs will be collected for 0-30 days. Additionally, SAE monitoring will be conducted from the start of vaccination until 6 months after the completion of the vaccination schedule. Furthermore, for fertile participants in the Phase I clinical trial, during the trial and after the first dose, pregnancy events of female participants themselves or the partners of male participants will be collected through a combination of active follow-up by researchers and self-reporting by participants.