Intranasal live attenuated influenza vaccine (LAIV; trade name FluMist/Fluenz-Tetra, manufactured by AstraZeneca/Medimmune) is the standard influenza vaccine given to children aged 2-17 years of age in the UK. It is also licensed to be given to adults up to the age of 49 years in the USA. The systems biology of the human blood response to influenza vaccines has been studied in great detail, but there is a paramount need to study innate and specific, soluble and cellular immune responses at the nasal mucosal site of influenza infection. In this way this study aims to determine correlates of efficacy and vaccine take in serum and nasal mucosal lining fluid (MLF).

This study will collect serial samples prior to vaccination and at intervals up to day 28 post-vaccination to establish the kinetics of the nasal mucosal and blood systemic response to LAIV in young adults aged 18-30 years (n=40). In the nose the investigators will measure viral load, soluble mediators of inflammation and antibodies (humoral immunity) in mucosal lining fluid; while cellular immune responses and serology will be assessed in blood samples. Investigators at Imperial College London (ICL) have been involved in the development of novel methods of non-invasive precision mucosal sampling, including absorption of MLF from the nose by nasosorption. The investigators have also developed assays for influenza-specific IgA by ELISA, and aim to compare this assay against a repertoire of serological assays in patients after LAIV administration.

The study will precisely assess mucosal and systemic immune responses to the LAIV nasal vaccine.

The primary endpoint will be based on nasal mucosal levels of IgA and IgG antibodies to the 4 constituent viral subtypes in LAIV: measured by ELISA and multiplex immunoassay (Mesoscale Diagnostics) and expressed as seroconversion rates, geometric mean titre (GMT) changes, and geometric mean fold rises (GMFR). The secondary endpoints will be: (1) haemagglutination inhibition (HAI) assay titres measured in serum and the nose, (2) influenza pseudotype neutralisation by antibodies in serum and the nose, (3) nasal cytokine and chemokine levels as measured by immunoassay and (4) nasal viral load quantified by qPCR.

It is thought that the immune response to LAIV in an individual is mediated by a combination of mucosal and systemic factors, involving innate and specific mechanisms that have different kinetics, and various cell types. By understanding the molecular and cellular basis of the nasal mucosal response to LAIV, the investigators hope to identify key molecular signatures and biomarkers associated with LAIV responses, and to assess protective pathways that could be stimulated by novel vaccines. The nasal vaccine challenge model could be used to test other new vaccines, and proceed to rational development of improved vaccines for influenza and other diseases. Furthermore nasal mucosal methods could be used in the clinic to identify subjects who have responded poorly to vaccines, or to assess vaccine efficacy in large populations.

Inclusion Criteria:

• Capacity to provide written informed consent
• Aged 18-30 years (inclusive)
• Fluent English speaker

Exclusion Criteria:

• Current involvement in another study unless observational or in follow-up phase (non-interventional)
• Received any influenza vaccine over the last 2 years
• Egg allergy
• Previous significant adverse reaction to any vaccination/immunisation
• Current regular (daily) smoker
• Pregnant
• Any medication that may affect the immune system (e.g. steroids)
• Taking regular acetylsalicylic acid (aspirin)
• Unable to give informed consent
• Current acute severe febrile illness
• Taking long term antibiotics
• Clinically diagnosed influenza in the last 2 years
• Any long-term health problem with heart disease, lung disease (including asthma), kidney disease, neurologic disease, liver disease, metabolic disease (e.g. diabetes) or anemia or another blood disorder
• Use of drugs for the treatment of rheumatoid arthritis, Crohn's disease, or psoriasis or anticancer drugs; or radiation treatments
• History of Guillain-Barre syndrome
• Live with or expect to have close contact with a person whose immune system is severely compromised and who must be in protective isolation (e.g., an isolation room of a bone marrow transplant unit)
• Received any other vaccinations in the past 4 weeks

IPD sharing is available upon request to the study PI; but access is offered at the discretion of the PI and requests are not guaranteed access. All access will require ethical approval.

From June 2020 onward, no set end date

PI discretion

The baseline population does not differ from the Participant Flow.

1 month study duration for vaccine arm, 1 day for placebo control arm.