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

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

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.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Intranasal Influenza Live Attenuated Vaccine

• Study Type: Interventional
• Enrollment (Actual): 201
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Lianyungang, Jiangsu, China
      • Haizhou District Center for Disease Control and Prevention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: The immediate vaccination group.; Participants are assigned to receive one dose of 0.2 mL of intranasal live attenuated influenza vaccine immediately (Day 0)	Biological: Intranasal Influenza Live Attenuated Vaccine; This vaccine is produced by Changchun BCHT Biotechnology Co.
Experimental: The delayed vaccination group; Participants are assigned to receive one dose of 0.2 mL of intranasal live attenuated influenza vaccine after a delay (Day 28).	Biological: Intranasal Influenza Live Attenuated Vaccine; This vaccine is produced by Changchun BCHT Biotechnology Co.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Jiangsu Province Centers for Disease Control and Prevention
• Investigators: Principal Investigator: Jing-Xin Li, PhD, Jiangsu Provincial Center for Diseases Control and Prevention; Study Director: Jiangsu Provincial Center for Diseases Control and Prevention, Jiangsu Provincial Center for Diseases Control and Prevention

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2024
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): January 17, 2025

Study Registration Dates

• First Submitted: September 13, 2024
• First Submitted That Met QC Criteria: September 19, 2024
• First Posted (Actual): September 24, 2024

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 11, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Colonization; Gut Microbiota; Mucosal Immunity; Intranasal Influenza Live Attenuated Vaccine; Nasal Microbiota
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human; Biological Products; Complex Mixtures; Vaccines; Viral Vaccines; Influenza Vaccines
• Other Study ID Numbers: JSJKYMS001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No