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  • Journal article
    Sheerin D, Openshaw PJ, Pollard AJ, 2017,

    Issues in vaccinology: Present challenges and future directions.

    , European Journal of Immunology, Vol: 47, Pages: 2017-2025, ISSN: 0014-2980

    Vaccination is a principal and highly cost-effective means of controlling infectious diseases, providing direct protection against pathogens by conferring long-lasting immunological memory and inducing population-level herd immunity. Despite rapid ongoing progress in vaccinology, there remain many obstacles to the development and deployment of novel or improved vaccines; these include the underlying science of how to induce and sustain appropriate protective immune responses as well as bureaucratic, logistic and socio-political hurdles. The failure to distribute and administer existing vaccines to at-risk communities continues to account for a large proportion of infant mortality worldwide: almost 20 million children do not have access to basic vaccines and several million still die each year as a result. While emerging epidemic or pandemic diseases pose a significant threat to global health and prosperity, there are many infectious diseases which provide a continuous or cyclical burden on healthcare systems which also need to be addressed. Gaps in knowledge of the human immune system stand in the way of developing technologies to overcome individual and pathogenic variation. The challenges in tackling infectious disease and directions that the field of preventive medicine may take to improve the current picture of global health are the focus of this review.

  • Journal article
    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

    Group B streptococcus and respiratory syncytial virus are leading causes of infant morbidity and mortality worldwide. No licensed vaccines are available for either disease, but vaccines for both are under development. Severe respiratory syncytial virus disease can be prevented by passively administered antibody. The presence of maternal IgG antibody specific to respiratory syncytial virus is associated with reduced prevalence and severity of respiratory syncytial virus disease in the first few weeks of life, whereas maternal serotype-specific anticapsular antibody is associated with protection against both early-onset and late-onset group B streptococcus disease. Therefore, vaccination in pregnancy might protect infants against both diseases. This report describes what is known about immune protection against group B streptococcus and respiratory syncytial virus, identifies knowledge gaps regarding the immunobiology of both diseases, and aims to prioritise research directions in maternal immunisation.

  • 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

    Maternal immunisation has the potential to substantially reduce morbidity and mortality from infectious diseases after birth. The success of tetanus, influenza, and pertussis immunisation during pregnancy has led to consideration of additional maternal immunisation strategies to prevent group B streptococcus and respiratory syncytial virus infections, among others. However, many gaps in knowledge regarding the immunobiology of maternal immunisation prevent the optimal design and application of this successful public health intervention. Therefore, we did an innovative landscape analysis to identify research priorities. Key topics were delineated through review of the published literature, consultation with vaccine developers and regulatory agencies, and a collaborative workshop that gathered experts across several maternal immunisation initiatives—group B streptococcus, respiratory syncytial virus, pertussis, and influenza. Finally, a global online survey prioritised the identified knowledge gaps on the basis of expert opinion about their importance and relevance. Here we present the results of this worldwide landscape analysis and discuss the identified research gaps.

  • 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, MOSAIC investigators, Dong T, McCauley J, Liew FY, Taylor S, Zambon M, Barclay W, Cerundolo V, Openshaw PJ, McMichael AJ, Ho LPet 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

    In each influenza season, a distinct group of young, otherwise healthy individuals with no risk factors succumbs to life-threatening infection. To better understand the cause for this, we analyzed a broad range of immune responses in blood from a unique cohort of patients, comprising previously healthy individuals hospitalized with and without respiratory failure during one influenza season, and infected with one specific influenza A strain. This analysis was compared with similarly hospitalized influenza patients with known risk factors (total of n = 60 patients recruited). We found a sustained increase in a specific subset of proinflammatory monocytes, with high TNF-α expression and an M1-like phenotype (independent of viral titers), in these previously healthy patients with severe disease. The relationship between M1-like monocytes and immunopathology was strengthened using murine models of influenza, in which severe infection generated using different models (including the high-pathogenicity H5N1 strain) was also accompanied by high levels of circulating M1-like monocytes. Additionally, a raised M1/M2 macrophage ratio in the lungs was observed. These studies identify a specific subtype of monocytes as a modifiable immunological determinant of disease severity in this subgroup of severely ill, previously healthy patients, offering potential novel therapeutic avenues.

  • 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 is a minimally invasive diagnostic procedure for measurement of viral load and markers of mucosal inflammation in RSV bronchiolitis

    , The Journal of Infectious Diseases, Vol: 215, Pages: 1240-1244, ISSN: 1537-6613

    Background.Existing respiratory mucosal sampling methods are flawed, particularly in a pediatric bronchiolitis setting.Methods.Twenty-four infants with bronchiolitis were recruited: 12 were respiratory syncytial virus (RSV)–positive, 12 were RSV-negative. Infants were sampled by nasosorption and nasopharyngeal aspiration (NPA).Results.Nasosorption was well tolerated and identified all RSV+ samples. RSV load measured by nasosorption (but not NPA) correlated with length of hospital stay (P = .04) and requirement for mechanical ventilation (P = .03). Nasosorption (but not NPA) levels of interferon γ, interleukin 1β, CCL5/RANTES, and interleukin 10 (IL-10) were elevated in RSV+ bronchiolitis (all P < .05), furthermore CCL5 and IL-10 correlated with RSV load (P < .05).Conclusions.Nasosorption allowed measurement of RSV load and the mucosal inflammatory response in infants.

  • 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

    The viral attachment protein of RSV has many surprising features, especially its mimicry of fractalkine (CX3CL1). Zhivaki et al. (2017) now show that, in addition to using this homology to attach to ciliated cells, it activates human neonatal regulatory B cells, thereby inhibiting immunological responses.

  • Journal article
    Openshaw PJM, Chiu C, Culley FJ, Johansson Cet al., 2017,

    Protective and Harmful Immunity to RSV Infection

    , Annual Review of Immunology, Vol: 35, Pages: 501-532, ISSN: 0732-0582

    Respiratory syncytial virus (RSV) is an exceptional mucosal pathogen. It specializes in infection of the ciliated respiratory epithelium, causing disease of variable severity with little or no direct systemic effects. It infects virtually all children by the age of three years and then repeatedly infects throughout life; this it does despite relatively slight variations in antigenicity, apparently by inducing selective immunological amnesia. Inappropriate or dysregulated responses to RSV can be pathogenic, causing disease-enhancing inflammation that contributes to short- and long-term effects. In addition, RSV's importance as a largely unrecognized pathogen of debilitated older people is increasingly evident. Vaccines that induce nonpathogenic protective immunity may soon be available, and it is possible that different vaccines will be optimal for infants; older children; young to middle-age adults (including pregnant women); and elderly persons. At the dawn of RSV vaccination, it is timely to review what is known (and unknown) about immune responses to this fascinating virus.

  • Conference paper
    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: Elsevier, Pages: AB384-AB384, ISSN: 0091-6749
  • Journal article
    Schuijs MJ, Hartmann S, Selkirk ME, Roberts LB, Openshaw PJ, Schnoeller Cet al., 2016,

    The Helminth-Derived Immunomodulator AvCystatin Reduces Virus Enhanced Inflammation by Induction of Regulatory IL-10+ T Cells.

    , PLOS One, Vol: 11, ISSN: 1932-6203

    Respiratory Syncytial Virus (RSV) is a major pathogen causing low respiratory tract disease (bronchiolitis), primarily in infants. Helminthic infections may alter host immune responses to both helminths and to unrelated immune triggers. For example, we have previously shown that filarial cystatin (AvCystatin/Av17) ameliorates allergic airway inflammation. However, helminthic immunomodulators have so far not been tested in virus-induced disease. We now report that AvCystatin prevents Th2-based immunopathology in vaccine-enhanced RSV lung inflammation, a murine model for bronchiolitis. AvCystatin ablated eosinophil influx, reducing both weight loss and neutrophil recruitment without impairing anti-viral immune responses. AvCystatin also protected mice from excessive inflammation following primary RSV infection, significantly reducing neutrophil influx and cytokine production in the airways. Interestingly, we found that AvCystatin induced an influx of CD4+ FoxP3+ interleukin-10-producing T cells in the airway and lungs, correlating with immunoprotection, and the corresponding cells could also be induced by adoptive transfer of AvCystatin-primed F4/80+ macrophages. Thus, AvCystatin ameliorates enhanced RSV pathology without increasing susceptibility to, or persistence of, viral infection and warrants further investigation as a possible therapy for virus-induced airway disease.

  • Journal article
    Makris S, Bajorek M, Culley F, Goritzka M, Johansson Cet al., 2016,

    Alveolar Macrophages Can Control Respiratory Syncytial Virus Infection in the Absence of Type I Interferons

    , Journal of Innate Immunity, Vol: 8, ISSN: 1662-8128

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