Enhanced immunological assessment of influenza vaccine efficacy in immunocompromised patients

Our understanding of vaccine-induced immune responses that protect immunocompromised individuals from infection is poor. I hypothesise that an individual’s T cell response to influenza is a critical correlate of protection against future infection and/or disease severity. As such, this project will develop an immunity test that effectively measures both an individual’s T cell and antibody response generated to seasonal influenza viruses for implementation into both clinical trials / research studies of vaccine efficacy and clinical care to identify high-risk patients. This will be performed through the following key objectives:

Objective 1) Internal laboratory validation of blood test
This objective will validate and establish the T cell and serological assays for further development, ensuring they conform to in-vitro diagnostic standards. In addition, it will assess novel capillary blood draw devices for larger scale immunity assessments. 

Key outputs: Blood test that can accurately measure seasonal influenza-specific IFN--positive T cell and IgG responses to each individual strain of seasonal influenza virus. Alternative capillary blood draw device assessed for acceptability.                                                                                                        

Objective 2) Clinical validation study in patients with secondary immunodeficiency
In collaboration with Prof Alex Richter (University of Birmingham), blood samples obtained from the national STRAVINSKY and ‘Time-of-Day’ longitudinal cohort studies will be assessed for T cell responses and associated with patient influenza vaccine / infection status and outcome.

Key output: T cell assay validated for use on cryopreserved PBMC samples. Publication detailing initial assessment of influenza-specific T cell responses as a correlate of protection in vaccinated immunocompromised patients.                        

Objective 3) Clinical validation study in patients with multiple sclerosis (MS)
In collaboration with Dr Emma Tallantyre, the Wales Neuroscience Research Tissue Bank and neurologists at Cardiff & Vale UHB, people with MS receiving either ocrelizumab (anti-CD20) or natalizumab (anti-4 integrin) will be assessed for T cell and antibody responses generated following seasonal influenza vaccination and assessed over 2 years for durability of immune responses and infection status.                                                                                

Key output: Publication detailing efficacy of blood test at measuring influenza-specific T cell and IgG responses in immunocompromised MS patients receiving common disease-modifying treatments. Publication to include initial assessment of correlates of protection from influenza infection in this cohort.                            

Objective 4) Large scale clinical validation study in Welsh population
500 individuals who have previously consented to being involved on HealthWise Wales research studies will be offered an at-home capillary blood T cell and antibody test to assess responses generated following seasonal influenza vaccination and/or infection. These individuals will be followed-up for 12 months to associate immune responses with infection status and demographic parameters.                                                                                

Objective 5) Implementation of blood test into clinical practice and vaccine efficacy studies
The blood test will be commercialised through ImmunoServ, who will establish the necessary regulatory framework and laboratory staff / infrastructure to offer and perform the test across external research studies, clinical trials and within the NHS. ImmunoServ will leverage its pre-existing relationship with Cardiff & Vale UHB and NHS Innovation Labs, alongside its connections with MHRA and pharma developing influenza vaccines, offering a credible route to market.