Aideen C. Allen

Institut de Pharmacologie et de Biologie Structurale

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Kingston H. G. Mills

Trinity College Dublin

Alicja Misiak

Trinity College Dublin

Mieszko M. Wilk

Trinity College Dublin

Wladimir Malaga

Institut de Pharmacologie et de Biologie Structurale

Céline Berrone

Institut de Pharmacologie et de Biologie Structurale

Roland Brosch

Institut Pasteur

Philip Supply

Institut Pasteur de Lille

Christophe Guilhot

Institut de Pharmacologie et de Biologie Structurale

Caroline E. Sutton

Trinity College Dublin

Flavie Moreau

Merck (Germany)

Cooperative Institutions

Trinity College Dublin

Centre National de la Recherche Scientifique

University College Dublin

Immune Regulation (United Kingdom)

Institut de Pharmacologie et de Biologie Structurale

St. Vincent's University Hospital

Université de Toulouse

St. James's Hospital

Novartis (Italy)

Toscana Life Sciences

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From environmental bacteria to obligate pathogen: the study of adaptations enhancing the persistence of tuberculosis bacilli

Tuberculosis (2020)

Aideen C. Allen Wladimir Malaga Catherine Astarie‐Dequeker Ali Hassan Céline Berrone

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Persistence (discontinuity)

10.1183/13993003.congress-2020.2802

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Citations (0)

Vaccine-induced protective immunity to Bordetella pertussis

Aideen C. Allen

Pertussis vaccine

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Immunization with whole cell but not acellular pertussis vaccines primes CD4 T _RM cells that sustain protective immunity against nasal colonization with Bordetella pertussis

Emerging Microbes & Infections (2019)

Mieszko M. Wilk Lisa Borkner Alicja Misiak Lucy Curham Aideen C. Allen

Protective immunity wanes rapidly after immunization of children with acellular pertussis (aP) vaccines and these vaccines do not prevent nasal colonization or transmission of Bordetella pertussis in baboons. In this study, we examined the role of tissue-resident memory T (TRM) cells in persistent protective immunity induced by infection or immunization with aP and whole-cell pertussis (wP) vaccines in mice. Immunization of mice with a wP vaccine protected against lung and nasal colonization, whereas an aP vaccine failed to protect in the nose. IL-17 and IFN-γ-secreting CD69+CD4+ TRM cells were expanded in the lung and nasal tissue after B. pertussis challenge of mice immunized with wP, but not aP vaccines. However, previous infection induced the most persistent protection against nasal colonization and this correlated with potent induction of nasal tissue TRM cells, especially IL-17-secreting TRM cells. Blocking T cell migration to respiratory tissue during immunization with a wP vaccine impaired bacterial clearance, whereas transfer of TRM cells from convalescent or wP-immunized mice conferred protection to naïve mice. Our findings reveal that previous infection or wP vaccination are significantly more effective than aP vaccination in conferring persistent protective immunity against B. pertussis and that this is mediated by respiratory TRM cells.

Pertussis vaccine

Whooping cough

10.1080/22221751.2018.1564630

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Therapeutic Use of Vitamin D and its Analogues in Autoimmunity

Recent Patents on Inflammation & Allergy Drug Discovery (2012)

Jean M. Fletcher Sharee A. Basdeo Aideen C. Allen Pádraic J. Dunne

In recent years, there has been great interest in the role of vitamin D in a number of diverse human diseases including autoimmunity, allergy, infection, cardiovascular disease, chronic lung disease, transplantation and cancer. Vitamin D is best known for its role in calcium metabolism; however it also has potent immunomodulatory effects. Epidemiological studies suggest that vitamin D deficiency may be a significant risk factor for many diseases. Furthermore, there is accumulating evidence from experimental studies that vitamin D has anti-inflammatory effects. Recent studies have indicated that a surprisingly high proportion of people are vitamin D deficient, suggesting that vitamin D supplementation may be of benefit to human health. This review will focus on the role of vitamin D in autoimmune diseases, including multiple sclerosis, rheumatoid arthritis and diabetes. We will review the epidemiological and experimental evidence for the protective effects of vitamin D in autoimmunity, as well as the preliminary vitamin D intervention studies and the most recent patented vitamin D analogues. Keywords: Autoimmunity, immune modulation, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, vitamin D, analogues, cholecalciferol, bones

Ergocalciferol

10.2174/187221312798889239

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Citations (21)

A novel TLR2 agonist from Bordetella pertussis is a potent adjuvant that promotes protective immunity with an acellular pertussis vaccine

Mucosal Immunology (2014)

Aisling Dunne Lisa A. Mielke Aideen C. Allen Caroline E. Sutton Russell Higgs

Whooping cough

Pertussis vaccine

Lipopeptide

10.1038/mi.2014.93

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Citations (69)

From environmental bacteria to obligate pathogen: the study of adaptations enhancing the persistence of tuberculosis bacilli

Tuberculosis (2019)

Aideen C. Allen Wladimir Malaga Catherine Astarie‐Dequeker Ali Hassan Céline Berrone

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Human pathogen

Strain (injury)

10.1183/13993003.congress-2019.pa4598

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The immunology of Bordetella pertussis infection and vaccination

Oxford University Press eBooks (2018)

Mieszko M. Wilk Aideen C. Allen Alicja Misiak Lisa Borkner Kingston H. G. Mills

Bordetella pertussis causes whooping cough (pertussis), a severe and sometimes fatal respiratory infectious disease, especially in young infants. Pertussis can be prevented in infants and children by immunization with either whole-cell pertussis (wP) or acellular pertussis (aP) vaccines; however, its incidence is increasing in many countries despite high vaccine coverage. This resurgence in populations immunized with aP vaccines has been attributed to (1) genetic changes in circulating strains of B. pertussis resulting from vaccine-driven immune selection, (2) waning protective immunity due to poor induction of immunological memory, or (3) a failure of aP vaccines to induce the appropriate arm(s) of the cellular immune responses required to prevent infection. Studies in a baboon model have suggested that previous infection prevents reinfection as well as disease, whereas aP vaccines fail to prevent nasal colonization and transmission of B. pertussis. Studies in the mouse model have demonstrated that immunization with wP vaccines induces Th1 and Th17 responses, whereas aP vaccines promote Th2-skewed responses and high antibody titres. Thus, while aP vaccine-induced antibodies may prevent pertussis, they may not prevent nasal colonization or transmission. Emerging data have suggested that replacing alum with novel adjuvants based on pathogen-associated molecular patterns has the capacity to switch the responses induced with aP vaccines to the more protective Th1/Th17 responses and may also enhance immunological memory. It is likely that third-generation pertussis vaccines will be based on live attenuated bacteria or aP formulations with novel adjuvants, which prevent nasal and lung infection and induce sustained immunity through induction of memory T cells.

Whooping cough

Pertussis vaccine

10.1093/oso/9780198811879.003.0003

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Citations (2)

S-16

Cytokine (2014)

Kingston H. G. Mills Aideen C. Allen Sarah C. Edwards Niamh C. McGuinness Aoife McGinley

TLR9

TLR7

10.1016/j.cyto.2014.07.236

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Citations (3)

Sustained protective immunity against Bordetella pertussis nasal colonization by intranasal immunization with a vaccine-adjuvant combination that induces IL-17-secreting TRM cells

Mucosal Immunology (2018)

Aideen C. Allen Mieszko M. Wilk Alicja Misiak Lisa Borkner Dearbhla M. Murphy

Current acellular pertussis (aP) vaccines induce strong antibody and Th2 responses but fail to protect against nasal colonization and transmission of Bordetella pertussis. Furthermore, immunity wanes rapidly after immunization. We have developed a novel adjuvant combination (called LP-GMP), comprising c-di-GMP, an intracellular receptor stimulator of interferon genes (STING) agonist, and LP1569, a TLR2 agonist from B. pertussis, which synergistically induces production of IFN-β, IL-12 and IL-23, and maturation of dendritic cells. Parenteral immunization of mice with an experimental aP vaccine formulated with LP-GMP promoted Th1 and Th17 responses and conferred protection against lung infection with B. pertussis. Intranasal immunization with the same aP vaccine-induced potent B. pertussis-specific Th17 responses and IL-17-secreting respiratory tissue-resident memory (TRM) CD4 T cells, and conferred a high level of protection against nasal colonization as well as lung infection, which was sustained for at least 10 months. Furthermore, long-term protection against nasal colonization with B. pertussis correlated with the number of IL-17-secreting TRM cells in nasal tissue. Our study has identified an approach for inducing IL-17-secreting TRM cells that sustain sterilizing immunity against nasal colonization of mice with B. pertussis, and could form the basis of a third generation pertussis vaccine for humans.

Pertussis vaccine

10.1038/s41385-018-0080-x

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Citations (120)

Improved pertussis vaccines based on adjuvants that induce cell-mediated immunity

Expert Review of Vaccines (2014)

Aideen C. Allen Kingston H. G. Mills

Bordetella pertussis is a Gram-negative bacterium that causes the severe and sometimes lethal respiratory disease whooping cough in infants and children. There has been a recent resurgence in the number of cases of pertussis in several countries with high vaccine coverage. This has been linked with waning or ineffective immunity induced by current acellular pertussis vaccines. These acellular pertussis vaccines are formulated with alum as the adjuvant, which promotes strong antibody responses but is less effective at inducing Th1-type responses crucial for effective bacterial clearance. Studies in animal models have demonstrated that replacing alum with alternative adjuvants, such as toll-like receptor agonists, can promote more robust cell-mediated immunity and confer a high level of protection against infection following respiratory challenge.

Whooping cough

Pertussis vaccine

Alum

10.1586/14760584.2014.936391

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Citations (45)