Building Immune Defence Priority Research Programme Host - PowerPoint PPT Presentation

Building Immune Defence Priority Research Programme Host Institution

IMMUNE SYSTEM MICROBIOTA NUTRITION

When it is obvious that the goals cannot be reached don’t adjust the goals; adjust the action steps Confucius

Food-health relationships for respiratory immune defence against infection and pollution driven inflammation

 77% of Chinese consumers ranked ‘immune enhancement’ as important  The outbreak of severe acute respiratory syndrome (SARS), bird and swine flu coupled with Asia’s ageing population is driving the growth of the immune health F&B market  Air pollution crisis across Asia presents a threat to human health These perspectives suggest a potential high adoption rate for F&B solutions targeting respiratory immune defence

Building Immune Defence Team Immune defence against infection lead organisation. Elizabeth Forbes-Blom, Hazel Poyntz, Aurélie Gestin, Anna Mooney Irene Braithwaite, Nick Shortt, Jenny Sparks, Darmiga Thayabaran, Tess Ostapowicz Wayne Young Sally Poppitt, Amy Liu, Audrey Tay Amber Parry-Strong Sarah Elliott Pollution inflammation lead organisation. Roger Hurst, Odette Shaw, Greg Sawyer In consultation with the Immune Industry Reference Group; Consumers Insights and Science of Food research themes.

Building Immune Defence Overall goal: Fast-track opportunities for NZ companies to develop foods and beverages with scientifically validated immune defence benefits  Provide a causal relationship for the beneficial modulation of immune defence  Identify associated nutrition responsive biomarkers (established and new) of the physiological and immunological processes  Examine the efficacy of these biomarkers to respond to food interventions in mouse models

Building immune defence – Tranche 1 timeline F&B candidates identified across the programme and incorporated into research design IRG meetings Objective 3 Collaboration with the Consumer Insights and Science of Food programmes will support the design, development and testing of potential product solutions 2015-16 2016-17 2017-18 2018-19 Oct - Sept Oct - Sept Oct - Sept Oct - Mar

Building immune defence – Tranche 1 timeline F&B candidates identified across the programme and incorporated into research design IRG meetings Complete exploratory study Objective 1.1 Association of gut microbiota community types to antibody responses following seasonal flu vaccine. Objective 3 Collaboration with the Consumer Insights and Science of Food programmes will support the design, development and testing of potential product solutions 2015-16 2016-17 2017-18 2018-19 Oct - Sept Oct - Sept Oct - Sept Oct - Mar

Building immune defence – Tranche 1 timeline F&B candidates identified across the programme and incorporated into research design IRG meetings Objective 1.2 Systems immunology approach to predict magnitude of the human immune response integrated with data from Objective 1.1 (including biomarker identification) Objective 3 Collaboration with the Consumer Insights and Science of Food programmes will support the design, development and testing of potential product solutions 2015-16 2016-17 2017-18 2018-19 Oct - Sept Oct - Sept Oct - Sept Oct - Mar

Building immune defence – Tranche 1 timeline F&B candidates identified across the programme and incorporated into research design IRG meetings Objective 1.3 Pre-clinical mouse model of altered gut microbiota to examine the impact on immune defence following seasonal flu vaccination Lead food candidates examined in pre-clinical mouse model for efficacy to beneficially modulate immune defence following seasonal flu vaccine Objective 3 Collaboration with the Consumer Insights and Science of Food programmes will support the design, development and testing of potential product solutions 2015-16 2015-16 2016-17 2016-17 2017-18 2017-18 2018-19 Oct - Sept Oct - Sept Oct - Sept Oct - Sept Oct - Sept Oct - Sept Oct - Mar

Building immune defence – Tranche 1 timeline F&B candidates identified across the programme and incorporated into research design IRG meetings Objective 2 Two pre-clinical models of pollution exacerbated respiratory inflammation developed to enable the measurement of food-health relationships Lead food candidates examined in pre- clinical models for efficacy to beneficially modulate immune defence following pollution exposure Objective 3 Collaboration with the Consumer Insights and Science of Food programmes will support the design, development and testing of potential product solutions 2015-16 2016-17 2017-18 2018-19 Oct - Sept Oct - Sept Oct - Sept Oct - Mar

Building immune defence against respiratory tract infection  Influenza epidemics occur virtually every year

Building immune defence against respiratory tract infection  Influenza epidemics occur Psychological Systemic - Lethargy virtually every year -Fever - Reduced cognitive function  Link between reduced Nasopharynx -Runny nose productivity and cognitive -Sore Throat Respiratory impairment well recognised - Coughing Gastric - Nausea - Vomiting Intestinal - Diarrhoea

Building immune defence against respiratory tract infection  Influenza epidemics occur virtually every year China antibiotic consumption US antibiotic consumption  Link between reduced per person annually per person annually productivity and cognitive impairment well recognised  As a consequence, 75% of Chinese patients with seasonal influenza are prescribed antibiotics despite a lack of efficacy

Accumulating evidence indicates antibiotic use perturbs immune defence against influenza

Microbiota regulates immune defence against influenza virus infection Ichinohe T, Pang IK, Kumamoto Y, Peaper DR, Ho JH, Murray TS, Iwasaki A. PNAS 2011; 108(13):5354-5359 Abt MC, Osborne LC, Monticelli LA, Doering TA, Alenghat T et al . Immunity. 2012;37(1):158-170.

Gut microbiota is necessary for antibody responses to seasonal influenza vaccination Oh JZ, Ravindran R, Chassaing B, Carvalho FA, Maddur MS, Bower M, et al. Immunity 2014; 41(3):478-492

Commercial opportunity  Influenza epidemics occurring virtually every year  Link between reduced productivity China antibiotic consumption US antibiotic consumption and cognitive impairment well per person annually per person annually recognised Change the “antibiotic panacea” to F&B solutions that build  As a consequence, 75% of Chinese immune defence against respiratory tract infection patients with seasonal influenza are prescribed antibiotics despite a lack of efficacy  Accumulating evidence now indicates that antibiotic use perturbs immune defence against influenza

Foodstuff Metabolites Receptor Main role in immunity Gut homeostasis, GPR43 Acetate regulation of inflammation Propionate GPR41 Macrophage/DC biology Metabolic control Butyrate Fibre Gut homeostasis GPR109A Regulation of some Nicotinic inflammatory acid conditions Anti-inflammatory properties, Kynurenic GPR35 Tryptophan/ acid Role still unclear tyrosine metabolites GPR84 ? Pro-inflammatory Role unclear Medium chain fatty acids GPR40 Type 2 diabetes related receptor GPR120 Anti-inflammatory properties, Inhibition of TNF, IL-6 Omega-3 fatty acids GPR91 ? Pro-inflammatory Citric acid cycle succinate Slide courtesy of Charles Mackay

 Vaccination responses provide insight into the overall efficacy of the co-ordinated function of a wide range of immune processes  Increased numbers of individuals attaining acceptable antibody titres is an appropriate nutrition responsive biomarker

 Immune responses vary widely from person to person Nakaya, HI et al. Nature Immunology 2011 12 786-795. Tsang, JS et al. Cell 2014 157 499-513  Non-heritable factors have the greatest contribution to immune health and wellbeing Brodin, P et al . Cell 2015 160 37–47 Carr, EJ et al. Nature Immunology 2016 in press Baxter, AG et al. Genome Medicine 2015 7:29  Immune response to vaccination depends on baseline immune status Tsang, JS et al. Cell 2014 157 499-513 Carr, EJ et al. Nature Immunology 2016 in press  Baseline immune status is stable over an extended sampling period Orrù, V. et al. Cell 2013 155 242-256 Tsang, JS et al. Cell 2014 157 499-513 Brodin, P et al . Cell 2015 160 37–47 Carr, EJ et al. Nature Immunology 2016 in press

Building immune defence against influenza exploratory study Day 3 Day 7 125 participants 18-64yrs Day 28 Wk 26 Day 0 Day 24 – Day 28 Day -4 – Day 0 Day 21 – Day 27 Day -7 – Day -1

Building immune defence against influenza exploratory study  Started 01/04/16; as at 11 am today ~40 participants will have completed day 0  24/06/16: 500 visits and 750 samples (~26L blood and 250 faecal samples) Day 0 Day 3 Day 7 Day 28 Wk 26    HAI   Microbiota + food diaries    Gene expression   Cell subset flow    TIV-B cell ELISpot   ELISA