title: Perinatal Immunization With Vaccine-Grade Listeria monocytogenes Provides Protection Against Murine Th2 Airway Inflammation.
abstract: OBJECTIVE
  Asthma is a chronic respiratory disorder that leads to inflammation and narrowing of the airways. Its global prevalence has attained epidemic levels and treatment options that reach beyond temporary relief of symptoms are urgently needed. Since the processes leading to clinically symptomatic asthma start early in life, we set out to systematically evaluate a neonatal immunotherapeutic based on Listeria monocytogenes (Lm) for the control of allergic sensitization.
  
  
  METHODS
  We modified Lm to express the model allergen, ovalbumin (OVA), and tested the ability of neonatal immunization with this strain to control allergic sensitization in a mouse model of OVA-induced asthma. Mice were immunized as newborns with live or heat killed LmOVA or live Lm, followed 6 weeks later by allergic sensitization with OVA. In order to determine whether the TH1-polarizing effect of this vaccine vector inadvertently may exacerbate development of certain TH1-driven allergic diseases, mice immunized as newborns were assessed in a model of adult hypersensitivity pneumonitis (HP).
  
  
  RESULTS
  Both LmOVA and Lm-control vaccines were highly effective in providing long-lasting protection from airway inflammation after only one immunization given perinatally. Serum antibody levels and lung cytokine production suggest that this prophylactic strategy is associated with an allergen specific TH1-dominated response. Specifically, LmOVA vaccinated mice displayed significantly elevated OVA-specific serum IgG2a, but no difference in anti-OVA IgE antibodies and only slightly decreased anti-OVA IgG1 antibodies. Importantly, Lm-based neonatal vaccination did not exacerbate Th1/Th17 driven HP, arguing against broad spectrum immune skewing.
  
  
  CONCLUSIONS
  Our findings highlight the promise of early life Lm-based immunomodulatory interventions as a prophylactic strategy for allergic asthma.
authors.affiliation: Department of Experimental Medicine and Division of Infectious & Immunological Diseases, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Sheka Yagub
authors.initials: SY
authors.lastname: Aloyouni
authors.affiliation: Department of Experimental Medicine and Division of Infectious & Immunological Diseases, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Charis-Patricia
authors.initials: CP
authors.lastname: Segeritz
authors.affiliation: Department of Experimental Medicine and Division of Infectious & Immunological Diseases, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Sherrid
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gold
authors.affiliation: Department of Experimental Medicine and Division of Infectious & Immunological Diseases, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Daniela I M
authors.initials: DI
authors.lastname: Loeffler
authors.affiliation: Centre de Recherche de L'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Québec, Canada.
authors.forename: Marie-Renée
authors.initials: MR
authors.lastname: Blanchet
authors.affiliation: Department of Experimental Medicine and Division of Infectious & Immunological Diseases, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Bing
authors.initials: B
authors.lastname: Cai
authors.affiliation: University of British Columbia James Hogg Research Centre-Heart and Lung Institute, St. Paul's Hospital, Vancouver, British Columbia, Canada. ; Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hirota
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McNagny
authors.affiliation: Department of Experimental Medicine and Division of Infectious & Immunological Diseases, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Tobias R
authors.initials: TR
authors.lastname: Kollmann
keywords: Asthma; Extrinsic allergic; immune system; listeria monocytogenes; newborn; vaccines