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Sheka Yagub Aloyouni,Charis-Patricia Segeritz,Ashley M. Sherrid,Matthew J. Gold,Daniela I. M. Loeffler,Marie-Renée Blanchet,Bing Cai,Jeremy Hirota,Kelly M. McNagny,Tobias R. Kollmann 대한천식알레르기학회 2014 Allergy, Asthma & Immunology Research Vol.6 No.4
Purpose: Asthma is a chronic respiratory disorder that leads to inflammation and narrowing of the airways. Its global prevalence has attained epidemiclevels and treatment options that reach beyond temporary relief of symptoms are urgently needed. Since the processes leading to clinicallysymptomatic 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 neonatalimmunization with this strain to control allergic sensitization in a mouse model of OVA-induced asthma. Mice were immunized as newborns withlive or heat killed LmOVA or live Lm, followed 6 weeks later by allergic sensitization with OVA. In order to determine whether the TH1-polarizing effectof this vaccine vector inadvertently may exacerbate development of certain TH1-driven allergic diseases, mice immunized as newborns were assessedin a model of adult hypersensitivity pneumonitis (HP). Results: Both LmOVA and Lm-control vaccines were highly effective in providinglong-lasting protection from airway inflammation after only one immunization given perinatally. Serum antibody levels and lung cytokine productionsuggest that this prophylactic strategy is associated with an allergen specific TH1-dominated response. Specifically, LmOVA vaccinated mice displayedsignificantly 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.