Hvivo Plc · LSE:HVO
Hvivo — ERS International Congress 2019
18 slides from Hvivo's conference presentation, September 2019
Slide 1: Temporal relationships of cytokines, chemokines and cellular biomarkers during HRV infection in asthmatics
Temporal relationships of cytokines, chemokines and cellular biomarkers during Human Rhinovirus (HRV) infection in asthmatics Alex Mann, Alan Bell, Michael Ghebre
Slide 2: Conflict of interest disclosure
Conflict of interest disclosure qI have no real or perceived conflicts of interest that relate to this presentation. qI have the following real or perceived conflicts of interest that relate to this presentation: Affiliation / Financial interest Commercial Company Grants/research support: n/a Honora
Slide 3: Aims
Aims • Explore the clinical response to HRV infection in a population of mild intermittant Asthma • Identify baseline immunity markers to HRV induced Asthma worsening during infection • Investigate the relationship between blood cells, NELF and blood biomarkers/cytokines to clincal responses during
Slide 4: Study design
Study design 20 mild asthmatic subjects (GINA 1): • 13 given HRV and 11 became infected • 7 given diluent
Slide 5: Study design
Study design Symptoms V1 (3xdaily) V2 Clinical Data Lung function Challenge (PEF 4xdaily; Nasopharyngeal FEV1 2xdaily) swab Asthma control (ACQ Day 0 & 7) Nasosorption Virology (3xdaily) Neutralisation, Serum Cytokines / chemokines 20 mild asthmatic subjects (GINA 1): • 13 given HRV and 11 became in
Slide 6: Demographics and Baseline characteristics
Demographics and Baseline characteristics Age – 18-55 Gender – 5 Female/15 Male Atopic - skin prick test positive Sensitivity – Reversible + PC20<16 mg/ml Asthma Medication – SABA PRN Smoking history – non-smoker/< 10 pack yrs
Slide 7: Clinical Endpoint: Virology
Clinical Endpoint: Virology 11008 8 0008 88 111 0 01 01 0 11 11007 7 0007 77 111 ( lo g 1 0 c o p y n u m b e r / m L ) ( lo g 1 0 c o p y n u m b e r / m L ) 0 08 8 11 L )) L )) L) mL c o p y n u m b e r/ m L 10 10 10 100 66 1100 0006 66 e rr // m 111 m m 1 lo g g ( lo g lo g g / / e (( lo e (( lo
Slide 8: Clinical endpoints: ACQ change and intercorrelations
PEF LRT URT M a x im u m d a ily % c h a n g e in P E F D a ily S u m L o w e r R e s p ir a to r t y c a b S u m D a il y U p p e r R e s p ir a t o r t y fr o m b a s e lin e T ra c t s y m p to m s c o re (L R T ) T ra c t s y m p to m s c o re (U R T ) 0 2 4 6 8 10 12 14 16 18 20 22 24 0 .0 0 .5
Slide 9: Immune Biomarkers: Baseline Susceptibility
Immune Biomarkers: Baseline Susceptibility Higher BL blood eosinophils associated with greater LRTS for infected subjects with high (red) and low increases in ACQ (i.e. greater loss of asthma control) (blue) baseline NELF IL-5 p < 0 .0 5 0 .6 4 .0 D a ily s u m L o w e r R e s p ir a t o r y 3 .5 0
Slide 10: Immune Biomarkers: Baseline Susceptibility
Immune Biomarkers: Baseline Susceptibility Higher BL blood eosinophils associated with greater LRTS for infected subjects with high (red) increases in ACQ (i.e. greater loss of asthma control) and low (blue) baseline NELF IL-5 p < 0 .0 5 4 .0 D a ily s u m L o w e r R e s p ir a t o r y 0 .6 Type 2
Slide 11: Nasosorption biomarkers: post inoculation changes
Nasosorption biomarkers: post inoculation changes r = - 0.75 0 P E F m a x % f a ll f r o m b a s e lin e -5 Chemokines for IL-2 -1 0 Recruitment of immune cells activated T cells & NK cells -1 5 and inflammation, & allergic PEF: response • CXCL19 (MIG), r = - 0.75 -2 0 PEF: • CXCL11 (ITAC), r = - 0
Slide 12: Monocytes Neutrophils
L%:M% Neutrophils Monocytes M i n im u m L y m p h o c y t e % : M o n o c y t e % N e u t r o p h ils A b s o lu t e cc aa bb M o n o c y t e s A b s o lu t e r a t io v a lu e C h a n g e F r o m B a s e lin e C h a n g e F r o m B a s e lin e - 1 .0 - 0 .5 0 .0 0 .5 1 .5 2 .0 2 .5 3 .0 1 .0 1 .5
Slide 13: Clinical, Cellular, and Biomarker Response to Infection
Clinical, Cellular, and Biomarker Response to Infection PEF, LRT, and blood cell changes correlated with NELF chemokines/ cytokines Mono Neut L:M Recruitment of immune cells CCL8 X X and inflammation, & allergic CCL13 X X response CCL5 X CXCL10 X X X CXCL9 X X X Chemokines for IL-2 CXCL11 X X X acti
Slide 14: Blood and NELF biomarkers
NELF BLOOD CELLS S e r u m C C L 8 ( M C P - 2 ) f o ld c h a n g e B lo o d N e u t r o p h ils A b s o lu t e N E L F C C L 8 ( M C P - 2 ) f o ld c h a n g e f r o m b a s e lin e C h a n g e F r o m B a s e lin e f r o m b a s e lin e - 1 .0 - 0 .5 0 .0 0 .5 1 .5 2 .0 2 .5 3 .0 0 .5 1 2 4 8 16 0
Slide 15: Summary of findings
Summary of findings • Hypothesis generating challenge study using HRV-16 rhinovirus mild intermittent asthma • HRV infection induced asthma worsening (ACQ, LRT, PEF) • Asthma worsening was associated with: • Raised baseline type 2 immune pathway markers • Post-inoculation changes in • blood cells •
Slide 16: Clinical relevance and future direction
Clinical relevance and future direction • Within a well studied phenotype different clinical responses to infection associates with baseline characteristics and the subsequent immune response • Impacting on T2 pathways prior to viral infection may reduce exacerbation frequency, severity and duration
Slide 17: Acknowlegements
Acknowlegements Thankyou to all the volunteers hVIVO team: • Alex Mann • Alan Bell • Michael Ghebre • hVIVO delivery team, in particular: • Marco De Sa • Ganesh Balaratnam • Jane Gunter • Pawel Rucki • Olesya Rusyn To get in contact with us: • Laura Krizman Alex Mann: a.mann@hvivo.com Your trusted a
Slide 18: International Congress 2019 Madrid
INTERNATIONAL CONGRESS 2019 MADRID Spain, 28 September - 2 October