Ignite Creation Date:
2025-12-24 @ 6:37 PM
Ignite Modification Date:
2026-01-24 @ 10:58 PM
Study NCT ID:
NCT02972957
Status:
COMPLETED
Last Update Posted:
2020-02-21
First Post:
2016-11-17
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Study of Intranasal Live Attenuated Influenza Vaccine Immunogenicity and Associations With the Nasopharyngeal Microbiome Among Children in the Gambia
Sponsor:
London School of Hygiene and Tropical Medicine
Organization:
Study Overview
Official Title:
A Study of Intranasal Live Attenuated Influenza Vaccine Immunogenicity and Associations With the Nasopharyngeal Microbiome Among Children in the Gambia - The NASIMMUNE Study
Status:
COMPLETED
Status Verified Date:
2020-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NASIMMUNE
Brief Summary:
The live attenuated influenza vaccine (LAIV) is made up of weakened influenza viruses given into the nose and in early studies was shown to be better than the standard influenza vaccine at preventing infections in children. However, more recently, it has performed less well and it may also work less well in Sub-Saharan Africa. Not only do the investigators not know why this is, but the investigators also do not fully understand why LAIV produces stronger nasal antibody responses in some individuals but not others. Usually harmless bacteria that are present in participants noses can influence how our immune system works and variations in these may explain differences in how LAIV works. The project will recruit children given LAIV in the Gambia to gain further understanding of these issues.
The investigators will measure a variety of responses to LAIV, including genes that can change their expression early after vaccination and use advanced computational techniques to identify new relationships between these genes and other LAIV responses. The investigators will also see whether nasal bacterial profiles in children who respond to LAIV are different from those who do not. In addition, the investigators will alter these bacteria in a subset of children with antibiotics and see whether this affects both nasal gene expression and later responses to LAIV.
The investigators will measure a variety of responses to LAIV, including genes that can change their expression early after vaccination and use advanced computational techniques to identify new relationships between these genes and other LAIV responses. The investigators will also see whether nasal bacterial profiles in children who respond to LAIV are different from those who do not. In addition, the investigators will alter these bacteria in a subset of children with antibiotics and see whether this affects both nasal gene expression and later responses to LAIV.
Detailed Description:
Purpose The overall goal of this study is to conduct at detailed immunogenicity study of intranasal live attenuated influenza vaccine (LAIV; Nasovac-S, Serum Institute of India Pvt. Ltd.), including identification of early molecular signatures associated with a robust mucosal immune response. In addition, the study team will explore whether the nasopharyngeal microbiome influences this immune response and whether LAIV has an impact on the microbiome.
A total of 365 healthy children aged 24 - 59 months will be recruited in The Gambia for this study.
Background Both the burden of infection and use of influenza vaccines in children from sub-Saharan Africa (SSA) have been neglected. There are limited immunogenicity or efficacy data from SSA of the widely used Ann Arbor strain-derived LAIV. This LAIV was shown to have greater relative efficacy compared to inactivated influenza vaccine in children in early randomized-controlled trials. There has, however, been concern regarding lower vaccine effectiveness in the US in recent years.
The Serum Institute of India Pvt. Ltd. has recently developed a trivalent LAIV (Nasovac-S) via a WHO facilitated donation of a Russian-derived LAIV, with the intention of scaling up provision of LAIV to resource-limited settings. Based on initial safety and immunogenicity data, Nasovac-S was licensed in India and granted a WHO prequalification certificate in 2015. Two placebo-controlled efficacy studies using Nasovac-S were recently undertaken in Bangladesh and Senegal (in children aged 24 - 59 months and 24 - 71 months respectively), providing mixed and contrasting results. In Senegal, no efficacy was found against the circulating pandemic H1N1 influenza strain (-9.7%, 95% CI -62.6, 26.1). In Bangladesh the overall vaccine efficacy to vaccine-matched strains, in a study of identical design, was 57.5% (95% CI 43.6, 68.0), with efficacy against H1N1 and H3N2, 50.0% (95% CI 9.2, 72.5) and 60.4% (95% CI 44.8, 71.6) respectively. The reason for the discrepancy in these studies or the poorer performance of the H1N1 component is not clear and emphasizes the need to undertake detailed immunogenicity studies of this vaccine in SSA. On a wider note, the exact immunological mechanisms of action of LAIV are also under-explored.
Study type:
Interventional
Design:
All primary objectives will be addressed through the conduct of a phase 4, randomized, controlled clinical vaccine trial. A total of 330 healthy children aged 24 - 59 months will be enrolled into one of three groups of equal size (3 x 110 children):
(i) LAIV-vaccinated (Group A - blood sample at day 0, 2, 21) (ii) LAIV-vaccinated (Group B - blood sample at day 0, 7, 21) (iii) Control group (Group C)
The study is not blinded, but group allocation will be concealed from the investigator team and block randomization stratified by sex will be undertaken.
Two LAIV-vaccinated groups are included in order to achieve several exploratory objectives, which require blood sampling at different times following vaccination, whilst minimizing the number of times children are bled. The unvaccinated subjects will serve as a control group for the primary objective of assessing the impact of LAIV on the nasopharyngeal microbiome.
An additional 35 healthy children aged 24 - 59 months will be recruited in the 2nd phase of recruitment (approximately Jan - June 2018) to assess how modulation of the nasopharyngeal microbiome with antibiotics impacts the mucosal immunogenicity to LAIV. These subjects will be matched as closely as possible by pre-antibiotic nasopharyngeal microbiome profile, age and sex (in that order of preference), in an exploratory nested case-control study, to n = 35 children recruited in the main clinical trial.
Official title A Study of Intranasal Live Attenuated Influenza Vaccine Immunogenicity and Associations with the Nasopharyngeal Microbiome Among Children in the Gambia (The NASIMMUNE study)
Primary outcome measures
* To identify novel early systemic and mucosal molecular signatures following LAIV that are associated with subsequent robust nasal and oral influenza-specific immunoglobulin A (IgA) responses, in order to provide insight into the mechanisms of successful mucosal immunization
* To identify associations between nasopharyngeal microbiota and nasal and oral influenza-specific IgA responses post-LAIV in Gambian children, to explore whether microbiome variability can explain suboptimal immune responses in some individuals to live intranasal mucosal vaccines in Sub-Saharan Africa
* To establish whether LAIV impacts the nasopharyngeal microbiome, with a specific focus on the burden of S. pneumoniae
A total of 365 healthy children aged 24 - 59 months will be recruited in The Gambia for this study.
Background Both the burden of infection and use of influenza vaccines in children from sub-Saharan Africa (SSA) have been neglected. There are limited immunogenicity or efficacy data from SSA of the widely used Ann Arbor strain-derived LAIV. This LAIV was shown to have greater relative efficacy compared to inactivated influenza vaccine in children in early randomized-controlled trials. There has, however, been concern regarding lower vaccine effectiveness in the US in recent years.
The Serum Institute of India Pvt. Ltd. has recently developed a trivalent LAIV (Nasovac-S) via a WHO facilitated donation of a Russian-derived LAIV, with the intention of scaling up provision of LAIV to resource-limited settings. Based on initial safety and immunogenicity data, Nasovac-S was licensed in India and granted a WHO prequalification certificate in 2015. Two placebo-controlled efficacy studies using Nasovac-S were recently undertaken in Bangladesh and Senegal (in children aged 24 - 59 months and 24 - 71 months respectively), providing mixed and contrasting results. In Senegal, no efficacy was found against the circulating pandemic H1N1 influenza strain (-9.7%, 95% CI -62.6, 26.1). In Bangladesh the overall vaccine efficacy to vaccine-matched strains, in a study of identical design, was 57.5% (95% CI 43.6, 68.0), with efficacy against H1N1 and H3N2, 50.0% (95% CI 9.2, 72.5) and 60.4% (95% CI 44.8, 71.6) respectively. The reason for the discrepancy in these studies or the poorer performance of the H1N1 component is not clear and emphasizes the need to undertake detailed immunogenicity studies of this vaccine in SSA. On a wider note, the exact immunological mechanisms of action of LAIV are also under-explored.
Study type:
Interventional
Design:
All primary objectives will be addressed through the conduct of a phase 4, randomized, controlled clinical vaccine trial. A total of 330 healthy children aged 24 - 59 months will be enrolled into one of three groups of equal size (3 x 110 children):
(i) LAIV-vaccinated (Group A - blood sample at day 0, 2, 21) (ii) LAIV-vaccinated (Group B - blood sample at day 0, 7, 21) (iii) Control group (Group C)
The study is not blinded, but group allocation will be concealed from the investigator team and block randomization stratified by sex will be undertaken.
Two LAIV-vaccinated groups are included in order to achieve several exploratory objectives, which require blood sampling at different times following vaccination, whilst minimizing the number of times children are bled. The unvaccinated subjects will serve as a control group for the primary objective of assessing the impact of LAIV on the nasopharyngeal microbiome.
An additional 35 healthy children aged 24 - 59 months will be recruited in the 2nd phase of recruitment (approximately Jan - June 2018) to assess how modulation of the nasopharyngeal microbiome with antibiotics impacts the mucosal immunogenicity to LAIV. These subjects will be matched as closely as possible by pre-antibiotic nasopharyngeal microbiome profile, age and sex (in that order of preference), in an exploratory nested case-control study, to n = 35 children recruited in the main clinical trial.
Official title A Study of Intranasal Live Attenuated Influenza Vaccine Immunogenicity and Associations with the Nasopharyngeal Microbiome Among Children in the Gambia (The NASIMMUNE study)
Primary outcome measures
* To identify novel early systemic and mucosal molecular signatures following LAIV that are associated with subsequent robust nasal and oral influenza-specific immunoglobulin A (IgA) responses, in order to provide insight into the mechanisms of successful mucosal immunization
* To identify associations between nasopharyngeal microbiota and nasal and oral influenza-specific IgA responses post-LAIV in Gambian children, to explore whether microbiome variability can explain suboptimal immune responses in some individuals to live intranasal mucosal vaccines in Sub-Saharan Africa
* To establish whether LAIV impacts the nasopharyngeal microbiome, with a specific focus on the burden of S. pneumoniae
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: