Perinatal Immunization With Vaccine-Grade Listeria monocytogenes Provides Protection Against Murine Th2 Airway Inflammation.
10.4168/aair.2014.6.4.341
- Author:
Sheka Yagub ALOYOUNI
1
;
Charis Patricia SEGERITZ
;
Ashley M SHERRID
;
Matthew J GOLD
;
Daniela I M LOEFFLER
;
Marie Renee BLANCHET
;
Bing CAI
;
Jeremy HIROTA
;
Kelly M MCNAGNY
;
Tobias R KOLLMANN
Author Information
1. Department of Experimental Medicine and Division of Infectious & Immunological Diseases, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
- Publication Type:Original Article
- Keywords:
Asthma;
vaccines;
listeria monocytogenes;
immune system;
newborn;
Extrinsic allergic
- MeSH:
Adult;
Alveolitis, Extrinsic Allergic;
Animals;
Antibodies;
Asthma;
Hot Temperature;
Humans;
Immune System;
Immunization*;
Immunoglobulin E;
Immunoglobulin G;
Infant, Newborn;
Inflammation*;
Listeria monocytogenes*;
Lung;
Mice;
Ovalbumin;
Ovum;
Prevalence;
Vaccination;
Vaccines
- From:Allergy, Asthma & Immunology Research
2014;6(4):341-349
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: 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 T(H)1-polarizing effect of this vaccine vector inadvertently may exacerbate development of certain T(H)1-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 T(H)1-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.
