Effect of a Multi-strain Probiotic Formulation on Immune Response to Influenza Vaccination

Influenza Vaccine Clinical Trial

— FLUVAC21  

Official title:

Efficacy and Safety of a Multistrain Probiotic Formula to Boost the Immune Response to Influenza Virus Vaccination

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05157425
• Other study ID #: AB-FLUVAC21
• Status: Completed
• Phase: N/A
• Start date: October 26, 2021
• Est. completion date: May 31, 2022

Study information

• Verified date: July 2022
• Source: AB Biotics, SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Randomized clinical trial to determine whether a probiotic formulation containing 4 probiotic strains which belong to Lactiplantibacillus plantarum and Pediococcus acidilactici species can boost the immune response to influenza vaccination evaluated at 4 weeks in a population between 50 and 80 years of age. Secondary outcomes comprise evaluation of immune response at 8 weeks after vaccination, percentage of patients with seroconversion, incidence and duration of influenza-like infections and respiratory infections throughout a 4-month period and safety.

Description:

Double blind, randomized, placebo-controlled clinical trial to determine whether supplementation with a probiotic formulation containing 4 probiotic strains (L. plantarum CECT 30292, CECT7484, CECT7485 and P. acidilactici CECT7483) can improve immune response to seasonal influenza vaccination. Subjects with age comprised between 50 and 80 years who meet inclusion and exclusion criteria will be randomized 1:1 to one of the following study groups: one will receive probiotic formulation for 28 days (1 capsule/day) and the other will receive placebo, starting the same day of the influenza vaccination. Main study outcome will be immune response at 4 weeks after vaccination, which will be determined by analysis of specific IgG antibodies in serum against influenza A and B. Secondary outcomes comprise serum titers of specific IgG at 8 weeks after vaccination, percentage of patients with seroconversion at 4 and 8 weeks, evaluation of influenza-like infections or respiratory infections throughout a 4-month period and adverse events.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: May 31, 2022
• Est. primary completion date: February 28, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

Inclusion Criteria:

• Subjects 50 - 80 years old receiving seasonal Influenza vaccine in season 2021-2022
• Body mass index (BMI) 18.5-34.9 kg/m2
• Willing to provide informed consent
• Able to follow study procedures, according to the criteria of study investigator

Exclusion Criteria:

• Hypersensitivity to any of the components of influenza vaccine
• Previous influenza infection in the same season (from 01/09/2021)
• Having received influenza vaccination in the previous season less than 9 months before study entry (from 01/01/2021)
• Having received another vaccine -different from COVID19 vaccine- up to 1 month before study inclusion or planning to receive it 1 month after study inclusion
• Active infection at the moment of study entry as diagnosed by study physician
• History of severe allergic reactions (food and non-food), including severe asthma.
• Receiving immunosuppressant therapy, displaying neutropenia, lymphopenia, AIDS, immunoglobulin deficiency, active oncological disease.
• Daily ingestion of any food complement or food added with probiotics (including Actimel o similar products) 2 weeks before inclusion in the study
• Acute pancreatitis, short bowel syndrome or active inflammatory bowel disease
• Diagnosed from other pathologies that according to study physician may compromise the immunological function of the individual (such as immunodeficiencies, lupus, multiple sclerosis, among others)
• Having received antibiotic treatment in the previous month

Exclusion criteria during the study:

• Withdrawal from the study as per study investigator criteria, in case that study procedures are not followed by the participant
• In case of adverse event that prevents them from following study procedures or complying with the treatments under study.
• Failure to comply with study procedures: Complete less than 70% of the days in the patient's diary and/or take less than 80% of the days of the study products.
• Receive any of the unauthorized treatments indicated in the selection criteria, with the exception of antibiotics that will be allowed under medical prescription.

Related Conditions & MeSH terms

• Influenza Vaccine
• Influenza, Human

Intervention

Dietary Supplement:
• Food Supplement
Probiotic multistrain formulation containing Lactiplantibacillus plantarum CECT30292, CECT7484, CECT7485 and P. acidilactici CECT7483 for 28 days, starting the same day of influenza vaccination
• Placebo
One maltodextrin-containing capsule/day for 28 days, starting the same day of influenza vaccination

Locations

Country	Name	City	State
Spain	FIBAO- Fundación para la Investigación Biosanitaria de Andalucia Oriental	Granada
Spain	Hospital General de Granollers	Granollers	Barcelona
Spain	Hospital Parc Tauli	Sabadell	Barcelona
Spain	IDIAP Jordi Gol-Centro de Atención Primaria La Mina	Sant Adrià De Besòs	Barcelona
Spain	Mutua de Terrassa	Terrassa	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
AB Biotics, SA

Country where clinical trial is conducted

Spain, 

References & Publications (8)

Darbandi A, Asadi A, Ghanavati R, Afifirad R, Darb Emamie A, Kakanj M, Talebi M. The effect of probiotics on respiratory tract infection with special emphasis on COVID-19: Systemic review 2010-20. Int J Infect Dis. 2021 Apr;105:91-104. doi: 10.1016/j.ijid — View Citation

Harper A, Vijayakumar V, Ouwehand AC, Ter Haar J, Obis D, Espadaler J, Binda S, Desiraju S, Day R. Viral Infections, the Microbiome, and Probiotics. Front Cell Infect Microbiol. 2021 Feb 12;10:596166. doi: 10.3389/fcimb.2020.596166. eCollection 2020. Review. — View Citation

Lambert ND, Ovsyannikova IG, Pankratz VS, Jacobson RM, Poland GA. Understanding the immune response to seasonal influenza vaccination in older adults: a systems biology approach. Expert Rev Vaccines. 2012 Aug;11(8):985-94. Review. — View Citation

Lynn DJ, Benson SC, Lynn MA, Pulendran B. Modulation of immune responses to vaccination by the microbiota: implications and potential mechanisms. Nat Rev Immunol. 2022 Jan;22(1):33-46. doi: 10.1038/s41577-021-00554-7. Epub 2021 May 17. Review. — View Citation

Ng TWY, Cowling BJ, Gao HZ, Thompson MG. Comparative Immunogenicity of Enhanced Seasonal Influenza Vaccines in Older Adults: A Systematic Review and Meta-analysis. J Infect Dis. 2019 Apr 19;219(10):1525-1535. doi: 10.1093/infdis/jiy720. — View Citation

Trombetta CM, Remarque EJ, Mortier D, Montomoli E. Comparison of hemagglutination inhibition, single radial hemolysis, virus neutralization assays, and ELISA to detect antibody levels against seasonal influenza viruses. Influenza Other Respir Viruses. 2018 Nov;12(6):675-686. doi: 10.1111/irv.12591. Epub 2018 Aug 11. — View Citation

Yeh TL, Shih PC, Liu SJ, Lin CH, Liu JM, Lei WT, Lin CY. The influence of prebiotic or probiotic supplementation on antibody titers after influenza vaccination: a systematic review and meta-analysis of randomized controlled trials. Drug Des Devel Ther. 20 — View Citation

Zimmermann P, Curtis N. The influence of probiotics on vaccine responses - A systematic review. Vaccine. 2018 Jan 4;36(2):207-213. doi: 10.1016/j.vaccine.2017.08.069. Epub 2017 Sep 18. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	IgG antibodies against vaccine influenza antigens	Titer of specific total IgG antibodies against vaccine influenza A and B antigens at day 28	4 weeks (day 1 and day 28)
Secondary	IgG antibodies against vaccine influenza antigens	Titer of specific total IgG antibodies against vaccine influenza A and B antigens at day 56	8 weeks (day 1 and day 56)
Secondary	IgM antibodies against vaccine influenza antigens	Titer of specific total IgM antibodies against vaccine influenza A and B antigens at day 28 and 56	8 weeks (day 1 and day 56)
Secondary	Seroconversion	Percentage of patients with seroconversion (defined as 4 fold change in influenza IgG antibodies concentration compared to baseline) at day 28 and 56	8 weeks (day 1,day 28 and 56)
Secondary	Incidence of influenza like infections (ILI)	Cumulative incidence of influenza like infection (ILI), according to the European Diseases Prevention and Control Center (ECDC) criteria	16 weeks (day 1, day 56)
Secondary	Incidence of any other respiratory infections (including COVID-19)	Cumulative incidence of any other respiratory infections	16 weeks (day 1, day 56)
Secondary	Incidence of fever	Cumulative number of days with fever (> 37.5ºC)	16 weeks (day 1, day 56)
Secondary	Use of analgesics and antibiotics	Cumulative number of days using analgesics and antibiotics	16 weeks (day 1, day 56)
Secondary	Duration of vaccine-related symptoms: injection-site pain, swelling, redness	Duration (in days) of symptoms after receiving the flu vaccine.	1 week (day 1, day 7)
Secondary	Severity of vaccine-related symptoms: injection-site pain, swelling, redness	Severity of symptoms after receiving the flu vaccine. Measured on a 4-point scale: 0 = none , 1 = mild, 2 = moderate, and 3 = severe	1 week (day 1, day 7)
Secondary	Gastrointestinal symptoms	Gastrointestinal manifestations documented through questionnaire in participants diary. Measured on a 4-point scale: 0 = none , 1 = mild, 2 = moderate, and 3 = severe.	4 weeks (day 1, day 28)
Secondary	Adverse events	Frequency of adverse events reported in medical visits or patient diary	8 weeks (day 56)
Secondary	Albumin	Albumin concentration in blood	4 weeks (day 1, day 28)
Secondary	Alkaline phosphatase (ALP)	Alkaline phosphatase (ALP) concentration in blood	4 weeks (day 1, day 28)
Secondary	Gamma-glutamil transpeptidase (GGT)	Gamma-glutamil transpeptidase (GGT) concentration in blood	4 weeks (day 1, day 28)
Secondary	Aspartate aminotransferase (GOT)	Aspartate aminotransferase (AST) concentration in blood	4 weeks (day 1, day 28)
Secondary	Alanine aminotransferase (AST)	Aspartate aminotransferase (AST) concentration in blood	4 weeks (day 1, day 28)
Secondary	Basic hemogram	Blood cell count	4 weeks (day 1, day 28)