Imperial College London

Peter Openshaw - Professor of Experimental Medicine

Faculty of MedicineNational Heart & Lung Institute

Clinical Consul for the Faculty of Medicine
 
 
 
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Contact

 

+44 (0)20 7594 3854p.openshaw Website CV

 
 
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Assistant

 

Ms Gale Lewis +44 (0)20 7594 0944

 
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Location

 

353Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

284 results found

Shi T, Denouel A, Tietjen AK, Campbell I, Moran E, Li X, Campbell H, Demont C, Nyawanda BO, Chu HY, Stoszek SK, Krishnan A, Openshaw P, Falsey AR, Nair H, RESCEU Investigatorset al., 2019, Global Disease Burden Estimates of Respiratory Syncytial Virus-Associated Acute Respiratory Infection in Older Adults in 2015: A Systematic Review and Meta-Analysis., J Infect Dis

Respiratory syncytial virus-associated acute respiratory infection (RSV-ARI) constitutes a substantial disease burden in older adults aged ≥65 years. We aimed to identify all studies worldwide investigating the disease burden of RSV-ARI in this population. We estimated the community incidence, hospitalization rate, and in-hospital case-fatality ratio (hCFR) of RSV-ARI in older adults, stratified by industrialized and developing regions, using data from a systematic review of studies published between January 1996 and April 2018 and 8 unpublished population-based studies. We applied these rate estimates to population estimates for 2015 to calculate the global and regional burdens in older adults with RSV-ARI in the community and in hospitals for that year. We estimated the number of in-hospital deaths due to RSV-ARI by combining hCFR data with hospital admission estimates from hospital-based studies. In 2015, there were about 1.5 million episodes (95% confidence interval [CI], .3 million-6.9 million) of RSV-ARI in older adults in industrialized countries (data for developing countries were missing), and of these, approximately 14.5% (214 000 episodes; 95% CI, 100 000-459 000) were admitted to hospitals. The global number of hospital admissions for RSV-ARI in older adults was estimated at 336 000 hospitalizations (uncertainty range [UR], 186 000-614 000). We further estimated about 14 000 in-hospital deaths (UR, 5000-50 000) related to RSV-ARI globally. The hospital admission rate and hCFR were higher for those aged ≥65 years than for those aged 50-64 years. The disease burden of RSV-ARI among older adults is substantial, with limited data from developing countries. Appropriate prevention and management strategies are needed to reduce this burden.

JOURNAL ARTICLE

Shi T, Arnott A, Semogas I, Falsey AR, Openshaw P, Wedzicha JA, Campbell H, Nair H, RESCEU Investigatorset al., 2019, The Etiological Role of Common Respiratory Viruses in Acute Respiratory Infections in Older Adults: A Systematic Review and Meta-analysis., J Infect Dis

Acute respiratory tract infections (ARI) constitute a substantial disease burden in adults and elderly individuals. We aimed to identify all case-control studies investigating the potential role of respiratory viruses in the etiology of ARI in older adults aged ≥65 years. We conducted a systematic literature review (across 7 databases) of case-control studies published from 1996 to 2017 that investigated the viral profile of older adults with and those without ARI. We then computed a pooled odds ratio (OR) with a 95% confidence interval and virus-specific attributable fraction among the exposed (AFE) for 8 common viruses: respiratory syncytial virus (RSV), influenza virus (Flu), parainfluenza virus (PIV), human metapneumovirus (HMPV), adenovirus (AdV), rhinovirus (RV), bocavirus (BoV), and coronavirus (CoV). From the 16 studies included, there was strong evidence of possible causal attribution for RSV (OR, 8.5 [95% CI, 3.9-18.5]; AFE, 88%), Flu (OR, 8.3 [95% CI, 4.4-15.9]; AFE, 88%), PIV (OR, not available; AFE, approximately 100%), HMPV (OR, 9.8 [95% CI, 2.3-41.0]; AFE, 90%), AdV (OR, not available; AFE, approximately 100%), RV (OR, 7.1 [95% CI, 3.7-13.6]; AFE, 86%) and CoV (OR, 2.8 [95% CI, 2.0-4.1]; AFE, 65%) in older adults presenting with ARI, compared with those without respiratory symptoms (ie, asymptomatic individuals) or healthy older adults. However, there was no significant difference in the detection of BoV in cases and controls. This review supports RSV, Flu, PIV, HMPV, AdV, RV, and CoV as important causes of ARI in older adults and provides quantitative estimates of the absolute proportion of virus-associated ARI cases to which a viral cause can be attributed. Disease burden estimates should take into account the appropriate AFE estimates (for older adults) that we report.

JOURNAL ARTICLE

Shi T, Denouel A, Tietjen AK, Lee JW, Falsey AR, Demont C, Nyawanda BO, Cai B, Fuentes R, Stoszek SK, Openshaw P, Campbell H, Nair H, RESCEU Investigatorset al., 2019, Global and Regional Burden of Hospital Admissions for Pneumonia in Older Adults: A Systematic Review and Meta-Analysis., J Infect Dis

Pneumonia constitutes a substantial disease burden among adults overall and those who are elderly. We aimed to identify all studies investigating the disease burden among older adults (age, ≥65 years) admitted to the hospital with pneumonia. We estimated the hospital admission rate and in-hospital case-fatality ratio (CFR) of pneumonia in older adults, stratified by age and economic status (industrialized vs developing), with data from a systematic review of studies published from 1996 through 2017 and from 8 unpublished population-based studies. We applied these rate estimates to population estimates for 2015 to calculate the global and regional burden in older adults who would have been admitted to the hospital with pneumonia that year. We estimated the number of in-hospital pneumonia deaths by combining in-hospital CFRs with hospital admission estimates from hospital-based studies. We identified 109 eligible studies; 73 used clinical pneumonia as the case definition, and 36 used radiologically confirmed pneumonia as the case definition. We estimated that, in 2015, 6.8 million episodes (uncertainty range [UR], 5.8-8.0 episodes) of clinical pneumonia resulted in hospital admissions of older adults worldwide. The hospital admission rate increased with advancing age and was higher in men. The total disease burden was likely underestimated when using the definition of radiologically confirmed pneumonia. Based on data from 52 hospital studies reporting data on pneumonia mortality, we estimated that about 1.1 million in-hospital deaths (UR, 0.9-1.4 in-hospital deaths) occurred among older adults. The burden of pneumonia requiring hospitalization among older adults is substantial. Appropriate prevention and management strategies should be developed to reduce its impact.

JOURNAL ARTICLE

Dunning J, Blankley S, Hoang LT, Cox M, Graham CM, James PL, Bloom CI, Chaussabel D, Banchereau J, Brett SJ, Moffatt MF, O'Garra A, Openshaw PJM, Habibi MS, Johnston SL, Hansel TT, Levin M, Thwaites RS, Warner JO, Cookson WO, Gazzard BG, Hay A, McCauley J, Aylin P, Ashby D, Barclay WS, Elderfield RA, Nadel S, Herberg JA, Drumright LN, Garcia-Alvarez L, Holmes AH, Kon OM, Aston SJ, Gordon SB, Hussell T, Thompson C, Zambon MC, Baillie KJ, Hume DA, Simmonds P, Hayward A, Smyth RL, McNamara PS, Semple MG, Nguyen-Van-Tam JS, Ho L-P, McMichael AJ, Kellam P, Adamson WE, Carman WF, Griffiths MJet al., 2019, Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza (vol 19, pg 625, 2018), NATURE IMMUNOLOGY, Vol: 20, Pages: 373-373, ISSN: 1529-2908

JOURNAL ARTICLE

Ascough S, Vlachantoni I, Kalyan M, Haijema B-J, Wallin-Weber S, Dijkstra-Tiekstra M, Ahmed MS, van Roosmalen M, Grimaldi R, Zhang Q, Leenhouts K, Openshaw PJ, Chiu Cet al., 2019, Local and Systemic Immunity Against RSV Induced by a Novel Intranasal Vaccine: A Randomised, Double- Blind, Placebo-Controlled Trial., Am J Respir Crit Care Med

RATIONALE: Needle-free intranasal vaccines offer major potential advantages, especially against pathogens entering via mucosal surfaces. As yet, there is no effective vaccine against respiratory syncytial virus (RSV), a ubiquitous pathogen of global importance that preferentially infects respiratory epithelial cells; new strategies are urgently required. OBJECTIVES: Here, we report the safety and immunogenicity of a novel mucosal RSV F protein vaccine linked to an immunostimulatory bacterium-like particle (BLP). METHODS: In this phase I, randomised, double-blind placebo-controlled trial, 48 healthy volunteers aged 18-49 years were randomly assigned to receive placebo or SynGEM (low- or high-dose) intranasally by prime-boost administration. The primary outcome was safety and tolerability, with secondary objectives assessing virus-specific immunogenicity. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in adverse events between placebo and vaccinated groups. SynGEM induced systemic plasmablast responses and significant, durable increases in RSV-specific serum antibody in healthy seropositive adults. Volunteers given low-dose SynGEM (140 µg F, 2mg BLP) required a boost at day 28 to achieve plateau responses with a maximum fold-change of 2.4, whereas high-dose recipients (350 µg F, 5mg BLP) achieved plateau responses with a fold-change of 1.5 after first vaccination that remained elevated up to 180 days post-vaccination irrespective of further boosting. Palivizumab-like antibodies were consistently induced, but F protein site Ø-specific antibodies were not detected and virus-specific nasal IgA responses were heterogeneous, with strongest responses in individuals with lower pre-existing antibody levels. CONCLUSIONS: SynGEM is thus the first non-replicating intranasal RSV subunit vaccine to induce persistent antibody responses in human volunteers. Clinical trial registration available at www.clinicaltrials.gov, ID NCT02958540.

JOURNAL ARTICLE

Ascough S, Vlachantoni I, Kalyan M, Haijema BJ, Wallin-Weber S, Dijkstra-Tiekstra M, Ahmed MS, van Roosmalen M, Grimaldi R, Zhang Q, Leenhouts K, Openshaw P, Chiu Cet al., Local and systemic immunity against RSV induced by a novel intranasal vaccine (SynGEM), American Journal of Respiratory and Critical Care Medicine, ISSN: 1073-449X

Rationale:Needle-free intranasal vaccines offer major potential advantages, especially against pathogens entering via mucosal surfaces. As yet, there is no effective vaccine against respiratory syncytial virus (RSV), a ubiquitous pathogen of global importance that preferentially infects respiratory epithelial cells; new strategies are urgently required.Objectives:Here, we report the safety and immunogenicity of a novel mucosal RSV F protein vaccine linked to an immunostimulatory bacterium-like particle (BLP).Methods:In this phase I, randomised, double-blind placebo-controlled trial, 48 healthy volunteers aged 18-49 years were randomly assigned to receive placebo or SynGEM (low- or high-dose) intranasally by prime-boost administration. The primary outcome was safety and tolerability, with secondary objectives assessing virus-specific immunogenicity. Measurements and Main Results:There were no significant differences in adverse events between placebo and vaccinated groups. SynGEM induced systemic plasmablast responses and significant, durable increases in RSV-specific serum antibody in healthy seropositive adults. Volunteers given low-dose SynGEM (140 µg F, 2mg BLP) required a boost at day 28 to achieve plateau responses with a maximum fold-change of 2.4, whereas high-dose recipients (350 µg F, 5mg BLP) achieved plateau responses with a fold-change of 1.5 after first vaccination that remained elevated up to 180 days post-vaccination irrespective of further boosting. Palivizumab-like antibodies were consistently induced, but F protein site -specific antibodies were not detected and virus-specific nasal IgA responses were heterogeneous, with strongest responses in individuals with lower pre-existing antibody levels. Conclusions:SynGEM is thus the first non-replicating intranasal RSV subunit vaccine to induce persistent antibody responses in human volunteers.

JOURNAL ARTICLE

Helbig C, Williamson C, Fundberg J, Openshaw PJM, Fogdell-Hahn Aet al., 2018, Men and Women in Immunology: Closing the gap on gender parity?, EUROPEAN JOURNAL OF IMMUNOLOGY, Vol: 48, Pages: 1776-1779, ISSN: 0014-2980

JOURNAL ARTICLE

Thwaites RS, Coates M, Ito K, Ghazaly M, Feather C, Abdulla F, Tunstall T, Jain P, Cass L, Rapeport G, Hansel TT, Nadel S, Openshaw Pet al., 2018, Reduced Nasal Viral Load and IFN Responses in Infants with Respiratory Syncytial Virus Bronchiolitis and Respiratory Failure, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 198, Pages: 1074-1084, ISSN: 1073-449X

JOURNAL ARTICLE

Mazur NI, Higgins D, Nunes MC, Melero JA, Langedijk AC, Horsley N, Buchholz UJ, Openshaw PJ, McLellan JS, Englund JA, Mejias A, Karron RA, Simoes EAF, Knezevic I, Ramilo O, Piedra PA, Chu HY, Falsey AR, Nair H, Kragten-Tabatabaie L, Greenough A, Baraldi E, Papadopoulos NG, Vekemans J, Polack FP, Powell M, Satav A, Walsh EE, Stein RT, Graham BS, Bont LJet al., 2018, The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates, LANCET INFECTIOUS DISEASES, Vol: 18, Pages: E295-E311, ISSN: 1473-3099

JOURNAL ARTICLE

Swieboda D, Thwaites R, Nadel S, Hansel T, Openshaw P, Culley Fet al., 2018, The role of innate lymphoid cells in early life lung infection, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

CONFERENCE PAPER

Barclay W, Openshaw P, 2018, The 1918 Influenza Pandemic: one hundred years of progress, but where now?, LANCET RESPIRATORY MEDICINE, Vol: 6, Pages: 588-589, ISSN: 2213-2600

JOURNAL ARTICLE

Dunning J, Blankley S, Hoang LT, Cox M, Graham CM, James PL, Bloom CI, Chaussabel D, Banchereau J, Brett SJ, Moffatt MF, O'Garra A, Openshaw PJMet al., 2018, Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza, NATURE IMMUNOLOGY, Vol: 19, Pages: 625-+, ISSN: 1529-2908

JOURNAL ARTICLE

Schwarze J, Openshaw P, Jha A, del Giacco SR, Firinu D, Tsilochristou O, Roberts G, Selby A, Akdis C, Agache I, Custovic A, Heffler E, Pinna G, Khaitov M, Nikonova A, Papadopoulos N, Akhlaq A, Nurmatov U, Renz H, Sheikh A, Skevaki Cet al., 2018, Influenza burden, prevention, and treatment in asthma-A scoping review by the EAACI Influenza in asthma task force, ALLERGY, Vol: 73, Pages: 1151-1181, ISSN: 0105-4538

JOURNAL ARTICLE

Thwaites RS, Gunawardana NC, Broich V, Mann EH, Ahnstrom J, Campbell GA, Lindsley S, Singh N, Tunstall T, Lane DA, Openshaw PJ, Hawrylowicz CM, Hansel TTet al., 2018, Biphasic activation of complement and fibrinolysis during the human nasal allergic response, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 141, Pages: 1892-+, ISSN: 0091-6749

JOURNAL ARTICLE

Tripp RA, Power UF, Openshaw PJM, Kauvar LMet al., 2018, Respiratory Syncytial Virus: Targeting the G Protein Provides a New Approach for an Old Problem, JOURNAL OF VIROLOGY, Vol: 92, ISSN: 0022-538X

JOURNAL ARTICLE

Petrarca L, Midulla F, Openshaw PJM, 2018, Vaccination policies in Europe: Common goals, diverse approaches and public doubts, EUROPEAN JOURNAL OF IMMUNOLOGY, Vol: 48, Pages: 10-12, ISSN: 0014-2980

JOURNAL ARTICLE

Jha A, Thwaites RS, Tunstall T, Kon OM, Shattock RJ, Openshaw PJ, Hansel TTet al., 2018, Human Nasal Challenge with TLR7/8 Agonist Resiquimod (R848) Induces Mucosal Interferon-alpha, with Increased Responsiveness in Asthmatic Volunteers, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

CONFERENCE PAPER

Thwaites RS, Jarvis HC, Singh N, Jha A, Pritchard A, Fan H, Tunstall T, Nanan J, Nadel S, Kon OM, Openshaw PJ, Hansel TTet al., 2018, Absorption of Nasal and Bronchial Fluids: Precision Sampling of the Human Respiratory Mucosa and Laboratory Processing of Samples, JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, ISSN: 1940-087X

JOURNAL ARTICLE

Sheerin D, Openshaw PJM, Pollard AJ, 2017, Issues in vaccinology: Present challenges and future directions, EUROPEAN JOURNAL OF IMMUNOLOGY, Vol: 47, Pages: 2017-2025, ISSN: 0014-2980

JOURNAL ARTICLE

Vlachantoni I, Ascough S, Grimaldi R, Leenhouts K, Chiu C, Openshaw Pet al., 2017, PHASE 1 TRIAL OF AN INTRANASAL RESPIRATORY SYNCYTIAL VIRUS (RSV) SUBUNIT CANDIDATE VACCINE: SAFETY RESULTS FROM THE MUC-SYNGEM STUDY, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A43-A44, ISSN: 0040-6376

CONFERENCE PAPER

Jha A, Jarvis H, Fraser C, Openshaw PJMet al., 2017, Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) infection has an estimated global incidence of 33 million cases in children younger than 5 years, with 10% requiring hospital admission and up to 199,000 dying of the disease. There is growing evidence that severe infantile RSV bronchiolitis, a condition characterised by an inflammatory reaction to the virus, is associated with later childhood wheeze in some vulnerable children; however, a direct causal relationship with asthma has not yet been established. It is also increasingly recognised as a cause of morbidity and mortality in those with underlying airway disease, immunocompromise and frail elderly persons. Novel molecular based diagnostic tools are becoming established but treatment largely remains supportive, with palivizumab being the only licensed agent currently available for passive prophylaxis of selected pre-term infants. Whilst effective treatments remain elusive, there is optimism about the testing of novel antiviral drugs and the development of vaccines that may induce long-lasting immunity without the risk of disease augmentation.

BOOK CHAPTER

Heath PT, Culley FJ, Jones CE, Kampmann B, Le Doare K, Nunes MC, Sadarangani M, Chaudhry Z, Baker CJ, Openshaw PJMet al., 2017, Group B streptococcus and respiratory syncytial virus immunisation during pregnancy: a landscape analysis, LANCET INFECTIOUS DISEASES, Vol: 17, Pages: E223-E234, ISSN: 1473-3099

JOURNAL ARTICLE

Marchant A, Sadarangani M, Garand M, Dauby N, Verhasselt V, Pereira L, Bjornson G, Jones CE, Halperin SA, Edwards KM, Heath P, Openshaw PJ, Scheifele DW, Kollmann TRet al., 2017, Maternal immunisation: collaborating with mother nature, LANCET INFECTIOUS DISEASES, Vol: 17, Pages: E197-E208, ISSN: 1473-3099

JOURNAL ARTICLE

Thwaites RS, Ito K, Chingono JMS, Coates M, Jarvis HC, Tunstall T, Anderson-Dring L, Cass L, Rapeport G, Openshaw PJ, Nadel S, Hansel TTet al., 2017, Nasosorption as a Minimally Invasive Sampling Procedure: Mucosal Viral Load and Inflammation in Primary RSV Bronchiolitis, JOURNAL OF INFECTIOUS DISEASES, Vol: 215, Pages: 1240-1244, ISSN: 0022-1899

JOURNAL ARTICLE

Cole SL, Dunning J, Kok WL, Benam KH, Benlahrech A, Repapi E, Martinez FO, Drumright L, Powell TJ, Bennett M, Elderfield R, Thomas C, Dong T, McCauley J, Liew FY, Taylor S, Zambon M, Barclay W, Cerundolo V, Openshaw PJ, McMichael AJ, Ho L-Pet al., 2017, M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza, JCI INSIGHT, Vol: 2, ISSN: 2379-3708

JOURNAL ARTICLE

Fraser CS, Jha A, Openshaw PJM, 2017, Vaccines in the Prevention of Viral Pneumonia, CLINICS IN CHEST MEDICINE, Vol: 38, Pages: 155-+, ISSN: 0272-5231

JOURNAL ARTICLE

Openshaw PJM, 2017, RSV Takes Control of Neonatal Breg Cells: Two Hands on the Wheel, IMMUNITY, Vol: 46, Pages: 171-173, ISSN: 1074-7613

JOURNAL ARTICLE

Thwaites RS, Gunawardana NC, Broich VL, Mann EH, Campbell GA, Tunstall T, Lindsley S, Hawrylowicz CM, Openshaw PJM, Hansel TTet al., 2017, Activation of the Complement, Coagulation and Fibrinolysis Pathways after Nasal Allergen Challenge, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB384-AB384, ISSN: 0091-6749

CONFERENCE PAPER

Openshaw PJM, Chiu C, Culley FJ, Johansson Cet al., 2017, Protective and Harmful Immunity to RSV Infection, ANNUAL REVIEW OF IMMUNOLOGY, VOL 35, Vol: 35, Pages: 501-532, ISSN: 0732-0582

JOURNAL ARTICLE

Gunawardana N, Campbell G, Lindsley S, Thwaites R, Mann E, Tunstall T, Openshaw P, Johnston S, Hawrylowicz C, Hansel Tet al., 2016, The effect of vitamin D supplementation on cathelicidin levels, vitamin D receptor (VDR) and E-cadherin expression after nasal allergen challenge in allergic rhinitis, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY-BLACKWELL, Pages: 1666-1666, ISSN: 0954-7894

CONFERENCE PAPER

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