The Interaction Between Mucosal Microbiota Colonization and the Immune Response to an Intranasal Influenza Live Attenuated Vaccine

Phase 4

Completed

• Conditions: Influenza
• Interventions: Biological: Intranasal Influenza Live Attenuated Vaccine

• Registration Number: NCT06609811
• Lead Sponsor: Jiangsu Province Centers for Disease Control and 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-09-13
• Study First Submitted QC: 2024-09-19
• Study Start: 2024-09-21
• Study First Posted: 2024-09-24
• Primary Completion: 2024-12-31
• Study Completion: 2025-01-17
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-20
• Last Update Posted: 2025-04-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
The immediate vaccination group.	Intranasal Influenza Live Attenuated Vaccine	Participants are assigned to receive one dose of 0.2 mL of intranasal live attenuated influenza vaccine immediately (Day 0)
The delayed vaccination group	Intranasal Influenza Live Attenuated Vaccine	Participants are assigned to receive one dose of 0.2 mL of intranasal live attenuated influenza vaccine after a delay (Day 28).

Primary Outcome Measures

Name	Time	Method
The level of sIgA antibodies (ng/mL) against the vaccine strain in nasal secretions at 28 days post-vaccination	Day 28 post-vaccination	Measured by Meso Scale Discovery
Changes in the density of nasal mucosal bacterial colonization (CFU/mL) compared to baseline	Day 28 post-vaccination	Measured by 16s RNA or metagenomic analysis
Changes in the abundance (α Diversity and β Diversity) of nasal mucosal bacterial colonization compared to baseline	Day 28 post-vaccination	Measured by 16s RNA or metagenomic analysis

Secondary Outcome Measures

Name	Time	Method
Changes in the abundance (α Diversity and β Diversity) of gut bacterial colonization compared to baseline	Day 28 post-vaccination	Measured by 16s RNA or metagenomic analysis
The incidence of adverse events (AEs) within 28 days post-vaccination	within 28 days post-vaccination
The level of neutralizing antibodies (NT50 and IC50, ng/mL) against the vaccine strain in serum at 28 days post-vaccination	Day 28 post-vaccination	Measured by Neutralization Assay
Changes in the density of gut bacterial colonization (CFU/mL) compared to baseline	Day 28 post-vaccination	Measured by 16s RNA or metagenomic analysis
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)	Day 28 post-vaccination	The number of IFN-γ secreting cells will be quantified using an ELISpot assay.
Frequency of activated T-cell subsets in nasal mucosal epithelial cells at Day 28 post-vaccination (Exploratory)	Day 28 post-vaccination	The phenotype and activation status of local mucosal T-cell subsets were measured by flow cytometry.

Trial Locations

Locations (1)

Haizhou District Center for Disease Control and Prevention; 🇨🇳 Lianyungang, Jiangsu, China