Vaccine 25 (2007) 7206–7216 Control of allergic reactions in mice by an active anti-murine IL-4 immunization H´ el` ene Le Buanec a,b , S´ ebastien Paturance c , Isabelle Couillin d , Silvia Schnyder-Candrian d , Patrick Larcier a , Bernhard Ryffel d , Bernard Bizzini a , Armand Bensussan e,f , Ars` ene Burny b , Robert Gallo g , Daniel Zagury a,∗,1 , Gabriel Peltre h,1 a Neovacs, S.A. 3-5 Impasse Reille, F-75014 Paris, France b Universit´ e Libre de Bruxelles Belgique, Belgium c CNRS CDTA, 3B rue de la F´ erollerie, 45071 Orl´ eans Cedex 2, France d UMR6218 CNRS, Molecular Immunology, Institut Transgenose, 3B rue de la Ferollerie, F-45071 Orl´ eans Cedex 2, France e Institut National de la Sant´ e et de la Recherche M´ edicale (INSERM) U659, Cr´ eteil, France f Institut Mondor de M´ edecine Mol´ eculaire, Hˆ opital Henri Mondor, 51, Avenue du Mal de Lattre de Tassigny, F-94010 Cr´ eteil, France g Institute of Human Virology, University of Maryland, 725 West Lombard Street, Suite S307, Baltimore, MD 21201, USA h Ecole Sup´ erieure de Physique et Chimie Industrielles (ESPCI), Allergie et Environnement, 10 rue Vauquelin, F-75005 Paris, France Received 12 March 2007; received in revised form 6 July 2007; accepted 15 July 2007 Available online 3 August 2007 Abstract Pathogenesis of allergic inflammatory disorders is characterized by allergen-induced IgE stimulated by Th2 cytokines including mainly IL-4 overproduction. To counteract IL-4 effects in sensitized-BALB/c mice, we prepared an IL-4 derivative immunogen, made of KLH and murine IL-4 heterocomplex, termed mIL-4 kinoid. Murine IL-4 kinoid immunized mice produced high titer of anti-IL-4 neutralizing Abs. In contrast to KLH control immunization kinoid immunization reversed the allergic IgE:IgG ratio hallmark in rBet v 1a sensitized mice and reduced pulmonary eosinophil recruitment and bronchial hyperreactivity in Ova-sensitized mice. These data pave the way to alternative therapies to combat allergic conditions. © 2007 Elsevier Ltd. All rights reserved. Keywords: Allergy; IL-4; Kinoid vaccination 1. Introduction Allergy is a common disease which affects a large propor- tion of about 15–30% individuals all over the world. Clinical manifestations launched by allergenic compounds in atopic Abbreviations: 2ME, 2-mercaptoethanol; Ova, ovalbumin; mIL-4, murine Interleukine-4; KLH, keyhole limpet hemocyanin; rBet v 1a, recom- binant Betula verrucosa allergen 1a; Ab, antibody; IFA, incomplet Freund’s adjuvant; CaHPO 4 , calcium phosphate; S.C., subcutaneous; I.M., intramus- cular; I.P., intraperitoneal; I.N., intranasal; BAL, bronchoalveolar lavages; Penh, enhanced respiratory pause ∗ Corresponding author. Tel.: +33 153109301; fax: +33 153109303. E-mail address: dzagury@neovacs.com (D. Zagury). 1 These authors contributed equally. individuals are multiple. Pollen as well as house dust mites most often may trigger conjunctivitis, rhinitis and contribute to asthma. Food allergens, such as peanuts or eggs, may pro- voke vomiting, diarrhea and urticaria. Severe forms of allergy which occur particularly following insect stinging or drug injection include Quinck oedema and systemic anaphylactic shock that can result in death. Pathogenesis of allergic inflammatory disorders results from the exposure of the immune system to allergens that induce specific IgE Abs [1]. These Abs bind to high affinity receptors on mast cells and basophils and subsequent bridg- ing of these IgE by allergens may trigger cell degranulation leading to the release of vasoactive amines such as histamine or serotonine. These mediators are the cause of inflammatory 0264-410X/$ – see front matter © 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2007.07.029