Title: Influenza Immunology
Funder: Department of Health and Social Care

Abstract: The proposed work in this theme contributes to PHE’s mission of supporting the national strategy for the control of seasonal and pandemic influenza. We propose to address a key PHE priority area of determining effectiveness of newly licensed live attenuated influenza vaccines (LAIV). This builds on an existing collaboration between IC and PHE started in 2009 that brings together complementary strengths in establishing sample biobanks (IC) and technological knowhow of functional antibody assays (PHE) and cellular immunological expertise (IC) to develop improved approaches for national influenza surveillance. Aim 1: To develop and validate new methods for population based serology Specific objectives: Short term (1-2 years) 1. To develop a novel assay to detect anti-Neuraminidase antibody (NAI) and compare against existing functional (Haemagglutination Inhibition and Microneutralisation) serological assays 2. Establishment of a biobank of oral and nasal wash samples for future work. Medium term (2-3 years) 1. To assess the newly developed NAI assay (developed in Objective 1.1. above) as a correlate of LAIV-induced protection. 2. To validate our NAI assay through the International Consortium for the Standardization of Influenza SeroEpidemiology (CONSISE) 3. To assess the suitability of alternative specimen types such as oral fluids and nasal wash for analysis using these and traditional influenza serological assays (HI, MN, NAI) 4. To develop assays to determine LAIV-induced serum or oral fluid IgA levels. Long term (4-5 years) 1. To validate correlates of vaccine-induced protective immunity (developed in Objectives A&B) during routine national surveillance Aim 2: To develop assays to distinguish infection from vaccination Specific objectives: Medium term (2-3 years) 1. To develop assays using a variety of platforms (ELISAs, peptide microarrays) and targets (internal viral proteins) that can distinguish vaccination from infection Aim 3: To develop and validate novel cellular immune correlates of protective immunity against symptomatic influenza Specific objectives: Short term (1-2 years) 1. To validate a novel cellular immune correlate of protection in the setting of natural infection 2. To assess cellular immune responses (from A.1.) as correlates of LAIV-induced protection Long term (4-5 years) 1. To validate cellular correlates (identified in Objectives A.1. and A.2.) of protective immunity during routine national surveillance Aim 4: To develop a pathway for preparation of therapeutic monoclonal antibodies (MAbs) as a national resource Specific objectives: Short term (1-2 years) 1. Development of a protocol with ethical approval to obtain biological samples from individuals Medium term (2-3 years) 1. Collection of samples from vaccinated individuals to generate high-titre MAbs Long term (4-5 years) 1. To generate and characterise MAbs for therapeutic use in humans.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION);3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: INFECTION;INFLAMMATORY AND IMMUNE SYSTEM