A Clinical Trial of an Quadrivalent Inactivated Influenza Vaccine in Healthy Children Aged 6 to 35 Months

A Single-center, Randomized, Blinded, Positive Controlled Clinical Trial to Assess the Reactogenicity and Immunogenicity of a Quadrivalent Inactivated Influenza Vaccine in Healthy Participants Aged 6-35 Months

In this single-center, randomized, blinded, positive-controlled design, the investigators will assess the safety and immunogenicity of 2 doses of an inactivated quadrivalent influenza vaccine in children aged 6 to 35 months.

About 120 healthy participants are planned to be enrolled, of who 60 participants were enrolled in the low-dose group and 60 participants were enrolled in the high-dose group. In the low-dose group, participants were randomly (2:1:1) assigned to receive a quadrivalent inactivated influenza vaccine (IIV4) at 0.25 mL including A/H1N1, A/H3N2, B/Victoria, and B/Yamagata, and a trivalent inactivated influenza vaccine (IIV3) at 0.25 mL including A/H1N1, A/H3N2 and B/Victoria, and IIV3 at 0.25 mL including A/H1N1, A/H3N2, and B/Yamagata. In the high-dose group, participants were randomly (2:1:1) assigned to receive IIV4 at 0.5 mL, and IIV3 at 0.25 mL including A/H1N1, A/H3N2, and B/Victoria, and IV3 at 0.25 mL including A/H1N1, A/H3N2, and B/Yamagata. Subjects receive 2 doses of influenza vaccine 4 weeks apart.

The occurrence of adverse reactions within 30 minutes, the occurrence of adverse reactions within 28 days, and serious adverse events within 6 months after vaccination will be observed in all participants. For participants aged 24-35 months in each dose group, laboratory safety tests were measured before enrollment and on day 4 post each dose to assess any toxic effects. In addition, all subjects will be required to collect blood for HI antibody testing before the first dose of vaccination and 30 days after the second dose of vaccination.

Inclusion Criteria:

• Healthy infants and young children aged 6-35 months, provide vaccination certificate and birth medical certificate.
• The subject or legal guardian can provide with informed consent and sign the informed consent form.
• The subjects or legal guardians are able to and willing to use a thermometer, a scale and fill in a diary card/contact card as required, and be able to comply with the requirements of the clinical trial protocol to complete clinical research.

Exclusion Criteria:

1. st dose:

   • Axillary temperature>37.0℃
   • Participants aged 24-35 months, with abnormal blood routine, blood biochemical and urine routine indexes and judged by the researchers as having clinical significance.
   • Influenza within the past 3 months (confirmed clinically, serologically or microbiological).
   • Have previously received any influenza vaccine (registered or experimental) or planned to receive any influenza vaccine during the study.
   • Allergy to any component of the study vaccine, history of allergic reaction to eating eggs or using gentamicin sulfate.
   • History of severe allergies to any vaccines or drugs.
   • Preterm (delivered before 37 weeks of gestation), low birth weight (birth weight <2500g) infants (only for volunteers aged 6 months to 12 months).
   • Dystocia, suffocation rescue, nervous system damage history.
   • Congenital malformations or developmental disorders affecting organ function, genetic defects, severe malnutrition, etc..
   • Acute illness, severe chronic illness, or acute exacerbation of chronic illness on the day of vaccination.
   • History of vaccination with the live attenuated vaccine within 14 days prior to vaccination and other vaccination within 7 days.
   • Those receiving immune enhancement or inhibitor therapy within 3 months (continuous oral or infusion for more than 14 days).
   • Have congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia, or other autoimmune diseases.
   • History of asthma, unstable in the past two years requiring urgent treatment, hospitalization, intubation, oral or intravenous corticosteroids.
   • Receive blood or blood-related products within 3 months.
   • Have a medical history or family history of convulsion, epilepsy, encephalopathy and psychosis.
   • History of coagulation abnormalities (eg, coagulation factor deficiency, coagulation disorder)
   • Plan to relocate before the end of the study or to be away from home for an extended period of time during scheduled study visits
   • Participating in or planning to participate in other clinical trials in the near future
   • Abnormal laboratory test indicators, except for minor abnormalities that have no clinical significance as judged by the doctor.
   • The investigator judges any situation that is inappropriate to participate in this clinical trial

2. nd dose:

   • Severe allergic reaction after the first dose of the vaccine.
   • Serious adverse reactions causally related to the first dose of the vaccine.
   • After the first vaccination, newly discovered or newly occurred do not meet the first-dose inclusion criteria or meet the first-dose exclusion criteria will be determined by the investigator whether to continue participating in the study.
   • Other reasons for exclusion in the opinion of the investigator.