Host Institution. Building Immune Defence Priority Research Programme

Transcription

1 Host Institution Building Immune Defence Priority Research Programme

2 IMMUNE SYSTEM MICROBIOTA NUTRITION

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

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

5 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

6 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 Pollution inflammation lead organisation. Roger Hurst, Odette Shaw, Greg Sawyer Sarah Elliott In consultation with the Immune Industry Reference Group; Consumers Insights and Science of Food research themes.

7 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

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

9 Building immune defence Tranche 1 timeline IRG meetings F&B candidates identified across the programme and incorporated into research design Objective 1.1 Complete exploratory study 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 Oct - Sept Oct - Sept Oct - Sept Oct - Mar

10 Building immune defence Tranche 1 timeline IRG meetings F&B candidates identified across the programme and incorporated into research design 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 Oct - Sept Oct - Sept Oct - Sept Oct - Mar

11 Building immune defence Tranche 1 timeline IRG meetings F&B candidates identified across the programme and incorporated into research design 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 Oct Oct - Sept - Sept Oct Oct - Sept - Sept Oct Oct - Sept - Sept Oct - Mar

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

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

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

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

16 Accumulating evidence indicates antibiotic use perturbs immune defence against influenza

17 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): Abt MC, Osborne LC, Monticelli LA, Doering TA, Alenghat T et al. Immunity. 2012;37(1):

18 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):

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

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

22 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

23 Immune responses vary widely from person to person Nakaya, HI et al. Nature Immunology Tsang, JS et al. Cell Non-heritable factors have the greatest contribution to immune health and wellbeing Brodin, P et al. Cell Carr, EJ et al. Nature Immunology 2016 in press Baxter, AG et al. Genome Medicine :29 Immune response to vaccination depends on baseline immune status Tsang, JS et al. Cell Carr, EJ et al. Nature Immunology 2016 in press Baseline immune status is stable over an extended sampling period Orrù, V. et al. Cell Tsang, JS et al. Cell Brodin, P et al. Cell Carr, EJ et al. Nature Immunology 2016 in press

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

26 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) HAI Microbiota + food diaries Gene expression Cell subset flow TIV-B cell ELISpot Day 0 Day 3 Day 7 Day 28 Wk 26 ELISA

27 Building immune defence against influenza exploratory study Outcomes: Intra-individual responses as compared to baseline Inter-individual diversity Stool community types in NZ cohort Association to vaccine response > High/Low responder profile > Identify low responders > Identify biomarkers that predict immune response

28 Systems Immunology approach Measures immune response in broad and unbiased fashion Cell populations Gene expression Antibody response Baseline signatures Stool community type

29 Pre-clinical models to examine food-health relationships

30 Pre-clinical model of modern-day dysbiosis Seasonal flu vaccine Poor diet Nutritional intervention Positive control/benchmark food Lead food candidates Early-life antibiotic treatment Stress Measure immune responses

31 H-VN Management Team Acknowledgements Science Leadership Team and Gut and Immune Expert Panel Building Immune Defence Team Consumer Insights and Science of Food Teams Immune Defence Industry Reference Group