Immunogenicity and Safety of Butantan Quadrivalent Influenza Vaccine (Split Virion, Inactivated) in Infants and Children .

A Blind Randomized Clinical Trial, With Active Controls, to Evaluate the Immunogenicity and Safety of the Quadrivalent Influenza Vaccine (Split Virion, Inactivated) From Instituto Butantan, in Infants and Children Aged 6 to 35 Months.

This is a Phase III Randomized Clinical Trial, blind, multicenter, with active controls, to evaluate the immunogenicity and safety of the Quadrivalent Influenza Vaccine (split virion, inactivated) from Instituto Butantan, in two dose scheme (0.25ml and 0.50ml), in infants and children under 3 years of age.

The study will be carried out in multiple sites in Brazil, using a community-based recruitment strategy.

The study interventions are the Butantan Quadrivalent Influenza Vaccine (split virion, inactivated) in two dose scheme (QIV-IB/0.25ml and QIV-IB/0.50ml) and the active controls Butantan Trivalent Influenza Vaccine (split virion, inactivated) containing Influenza B virus - Victoria or Yamagata lineage (TIVV-IB and TIVY-IB), in a ratio 1:1:1:1.

The study population is healthy infants and children aged 6 to 35 months and all participants will be followed up 6 months after the last vaccination.

Inclusion Criteria:

1. Healthy infant and child of either sex aged between 6 and 35 months on the day of the first study vaccination.
2. Born at term (≥ 37 weeks of gestational age) and birth weight ≥ 2.5 kg.
3. Parents/legal guardians of the infant or child able and willing to attend all scheduled visits and comply with all study procedures, including blood draws.
4. Parents/legal guardians of the infant or child have provided informed consent.

Exclusion Criteria:

1. Having received any influenza vaccine from the current season and/or 6 months before the first study vaccination.
2. History of allergy to egg, chicken proteins, or other components of the influenza vaccine.
3. History of serious adverse reaction to any influenza vaccine.
4. Have any clinically significant condition or situation that, in the Investigator's opinion, would interfere with study evaluations or participation.
5. History of Guillain-Barré or other demyelinating diseases.
6. History of neurological disease and/or clinically significant developmental delay (at the discretion of the Investigator), or seizure (except for an isolated febrile seizure episode).
7. Having received immune globulin, blood, or any blood product 3 months before the planned date of the first study vaccination or planned administration during the study period.
8. Any confirmed or suspected immunosuppressive condition, congenital or acquired immunodeficiency (including human immunodeficiency virus - HIV) based on medical history and physical examination.
9. Immediate personal or family history of congenital immunodeficiency.
10. Having received or are using radiation therapy, chemotherapy, immunosuppressive drugs, or other immunomodulatory drugs within three months before the planned date of the first study vaccination or planned use during the study.
11. Be a solid organ or bone marrow/stem cell transplant recipient.
12. Thrombocytopenia, bleeding disorder, use of anticoagulants, or any condition that contraindicates intramuscular injection.
13. Significant chronic disease (cancer, autoimmune disease, diabetes mellitus, acute or progressive liver disease, acute or progressive kidney disease, severe heart or lung disease) or which in the Investigator's opinion poses a risk to the health of the infant or child participating in the study or which may interfere with the conduct or conclusion of the study.
14. History of seropositivity for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
15. Major surgery or surgery using general anesthesia planned to occur during the period between the first vaccination and 28 days after full vaccination in the study.
16. Any condition that, in the opinion of the Investigator, may interfere with the conduct or completion of the study (such as travelling or planned moving of residence, among others).
17. Participation in another clinical trial involving another experimental or unregistered product 1 year before the planned date of the study's first vaccination, or plans to entering a clinical trial during the study.
18. Infant and institutionalized child.
19. Be related to the Investigator, research site staff member, or employee directly involved in the study.

Postponement Criteria:

1. Have received any vaccine (including routine childhood vaccines) within 28 days of the first study vaccination (delay until the 28-day deadline from the date of the last vaccination).
2. Moderate or severe (as judged by the Investigator) acute illness/infection or febrile illness (temperature ≥ 37.8°C) 48 hours before the planned date of the first study vaccination.
3. Acute respiratory illness within 14 days preceding the planned date of the first study vaccination.