A Study of Intranasal Live Attenuated Influenza Vaccine Immunogenicity and Associations With the Nasopharyngeal Microbiome Among Children in the Gambia

• Status: Completed
• Trial end date: 2019-05-23
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: London School of Hygiene and Tropical Medicine; Medical Research Council Unit, The Gambia
• Collaborators: National Institute for Public Health and the Environment (RIVM); Public Health England; University of Edinburgh; University of Oxford
• Treatments: Azithromycin; Vaccines

Criteria

Inclusion Criteria:

• • Healthy male or female child at least 24 months of age and less than 60 months of age at the time of study entry.

• Resident in the study area and with no plans to travel outside the study area during the period of subject participation.

• Informed consent for the study participation obtained from a parent (or guardian only if neither parent is alive or if guardianship has been legally transferred (see section 11.2).

• Willingness and capacity to comply with the study protocol as judged by a member of the clinical trial team.

Exclusion Criteria:

• • Serious, active, medical condition, including but not limited to:

• chronic disease of any body system

• severe protein-energy malnutrition (weight-for-height Z-score of less than -3)

• known genetic disorders, such as Down's syndrome or other cytogenetic disorder

• Active wheezing

• History of documented hypersensitivity to eggs or other components of the vaccine (including gelatin, sorbitol, lactalbumin and chicken protein), or with life-threatening reactions to previous influenza vaccinations.

• History of documented hypersensitivity to macrolide antibiotics

• History of Guillain-Barré syndrome.

• Receipt of aspirin therapy or aspirin-containing therapy within the two weeks before planned study vaccination.

• Any suspected or confirmed congenital or acquired state of immune deficiency including but not limited to primary immunodeficiencies including thymus disorders, HIV/AIDS, hematological or lymphoid malignancies (blood tests will not be routinely undertaken with this regard as part of the study).

• Any current immunosuppressive/immunomodulatory treatment or receipt of any such treatment within the six months preceding trial enrolment (for corticosteroids this is defined as a dose of prednisolone (or equivalent) of greater than 2mg/kg/day for one week or 1mg/kg/day for one month. The use of topical corticosteroids is not an exclusion criterion.

• The use of inhaled corticosteroids within the last one month.

• Receipt of an influenza vaccine within the past 12 months.

• Has any condition determined by investigator as likely to interfere with evaluation of the vaccine or be a significant potential health risk to the child or make it unlikely that the child would complete the study.

• Any significant signs or symptoms of an acute illness or infection including:

• an axillary temperature of 38.0°C or above or documented fever of 38°C or above in the preceding 14 days.

• Any acute respiratory infection within 14 days of enrollment visit. If the reason for ineligibility is likely to be temporary (e.g. a fever of 38°C or above or acute respiratory infection) and either will or may resolve before the infant reaches 60 months, they will not be recorded as a screening failure but instead will be re-screened within an appropriate future time-window (e.g. at least 14 days after the last documented fever of 38°C or above or resolution of respiratory illness) and a decision made regarding eligibility at that point.