Clinical trial NCT06609811: The Interaction Between Mucosal Microbiota Colonization and the Immune Response to an Intranasal Influenza Live Attenuated Vaccine
Official title: The Interaction Between Mucosal Microbiota Colonization in the Nasal Cavity and Gut and the Immune Response to an Intranasal Influenza Live Attenuated Vaccine in Children and Adolescents Aged 6 to 17 Years: A Single-Center, Randomized, Open-Label Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Influenza
Keywords: Intranasal Influenza Live Attenuated Vaccine
Nasal Microbiota
Gut Microbiota
Colonization
Mucosal Immunity
Lead sponsor: Jiangsu Province Centers for Disease Control and Prevention
Sponsor class: NETWORK
First posted: 2024-09-24
Enrollment: 200
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a single-center, randomized, open-label trial designed to explore the interaction between mucosal microbiota colonization in the nasal cavity and gut and the immune response to an intranasal live attenuated influenza vaccine (LAIV). The study plans to enroll 200 children and adolescents aged 6-17 years, with approximately 50% in the 6-11 years age group and 50% in the 12-17 years age group. Participants and their guardians must be able and willing to comply with the clinical trial protocol and provide informed consent. Eligible participants will be randomly assigned in a 1:1 ratio, stratified by age groups, to either the immediate vaccination group or the delayed vaccination group. Nasal swabs will be collected for all participants of both the immediate vaccination group or the delayed vaccination group after randomization for the detection of nasal and gut microbiota. Then, the immediate vaccination group will receive one dose of 0.2 mL of LAIV 28 days after randomization, while the delayed vaccination group will receive one dose of 0.2 mL of LAIV 56 days after randomization. Blood and mucosal samples (nasal stool) will be collected on the day before vaccination and on 28 days after vaccination for humoral and mucosal immunogenicity analysis. Moreover, the occurrence of adverse events within 28 days after vaccination will be collected.


Eligibility criteria: Inclusion Criteria:

1. Individuals aged 6-17 years.
2. Volunteers and their guardians are able and willing to comply with the requirements of the clinical trial protocol and sign the informed consent form.

Exclusion Criteria:

1. Allergy to any component of the vaccine product, including eggs, excipients, or gentamicin sulfate.
2. Individuals with acute illnesses, severe chronic illnesses, acute exacerbations of chronic illnesses, or fever.
3. Pregnant or lactating women.
4. Individuals with Leigh syndrome who are receiving treatment with aspirin or aspirin-containing medications.
5. Individuals with immunodeficiency, immunosuppression, or those undergoing immunosuppressive therapy.
6. Individuals with uncontrolled epilepsy, other progressive neurological disorders, or a history of Guillain-Barré syndrome.
7. Individuals with rhinitis or asthma.
8. Individuals with a personal or family history of seizures, chronic diseases, epilepsy, or allergic tendencies.
9. Individuals who have received immunoglobulin injections within the last 3 months prior to vaccination.
10. Individuals who have used other live attenuated vaccines within 1 month prior to vaccination.
11. Individuals planning to use antiviral drugs for influenza within 48 hours before or 2 weeks after vaccination.
12. Individuals planning to use any other intranasal medication within 2 days after vaccination.

Primary outcomes:
measure: The level of sIgA antibodies (ng/mL) against the vaccine strain in nasal secretions at 28 days post-vaccination
timeFrame: Day 28 post-vaccination
measure: Changes in the density of nasal mucosal bacterial colonization (CFU/mL) compared to baseline
timeFrame: Day 28 post-vaccination
measure: Changes in the abundance (α Diversity and β Diversity) of nasal mucosal bacterial colonization compared to baseline
timeFrame: Day 28 post-vaccination
Secondary outcomes:
measure: The level of neutralizing antibodies (NT50 and IC50, ng/mL) against the vaccine strain in serum at 28 days post-vaccination
timeFrame: Day 28 post-vaccination
measure: Changes in the density of gut bacterial colonization (CFU/mL) compared to baseline
timeFrame: Day 28 post-vaccination
measure: Changes in the abundance (α Diversity and β Diversity) of gut bacterial colonization compared to baseline
timeFrame: Day 28 post-vaccination
measure: The incidence of adverse events (AEs) within 28 days post-vaccination
timeFrame: within 28 days post-vaccination
measure: Number of IFN-γ secreting cells in nasal mucosal epithelial cells in response to influenza virus-based synthetic peptide pools at Day 28 post-vaccination (Exploratory)
timeFrame: Day 28 post-vaccination
measure: Frequency of activated T-cell subsets in nasal mucosal epithelial cells at Day 28 post-vaccination (Exploratory)
timeFrame: Day 28 post-vaccination
Other outcomes:
Locations:
city: Lianyungang
country: China
facility: Haizhou District Center for Disease Control and Prevention
state: Jiangsu
Study officials:
affiliation: Jiangsu Provincial Center for Diseases Control and Prevention
name: Jing-Xin Li, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Jiangsu Provincial Center for Diseases Control and Prevention
name: Jiangsu Provincial Center for Diseases Control and Prevention
role: STUDY_DIRECTOR
References: