Abstract
The anti‐human immunoglobulin E (IgE) monoclonal antibody, omalizumab (Xolair®, Genentech, South San Fransisco, CA), is effective in the treatment of poorly controlled moderate to severe allergic asthma and chronic idiopathic urticaria. It acts by specifically binding to the constant domain (Cϵ3) of free human IgE in the blood and interstitial fluid. Although efficacious, use of omalizumab is limited due to restrictions on patient weight and pre‐existing IgE levels, and frequent dosing (q2–4 weeks). A vaccine inducing anti‐IgE antibodies has the potential for similar clinical benefits with less frequent dosing and relatively lower cost of goods. We developed a vaccine containing two IgE peptide‐conjugates targeting the Cϵ3 domain of human IgE. As part of preclinical evaluation of the vaccine to optimize formulation and dose prior to initiating clinical studies, we evaluated the vaccine in non‐human primates, and demonstrate the induction of anti‐peptide antibodies that can bind to conformationally intact human IgE and are capable, at least in some animals, of substantial lowering circulating IgE levels.
Highlights
The incidence of immunoglobulin E (IgE)-mediated allergic conditions, including allergic asthma and rhinitis, has significantly increased over the last few decades, resulting in significant morbidity and mortality and associated costs [1]
Using plates coated with human C3C4, it was found that a small number of monkeys (6%) had a low level of pre-existing anti-IgE, these pre-existing titers did not appear to interfere with vaccine immunogenicity and all animals showed an increase in anti-IgE titers post vaccination relative to baseline (Fig. 1)
The Qb-virus-like particle (VLP) has been administered in clinical trials for other indications, for example conjugated to a peptide from angiotensin II for treatment of hypertension (CYT006-AngQb) [44] or conjugated with a nicotine-like hapten for smoking cessation (CYT002-NicQb) [45, 46]
Summary
The incidence of IgE-mediated allergic conditions, including allergic asthma and rhinitis, has significantly increased over the last few decades, resulting in significant morbidity and mortality and associated costs [1]. In the US, the Center for Disease Control and Prevention reported a 73.9% increase in self-reported asthma during the period from 1980 to 1996 [2,3,4]. Allergen-specific IgE binds to the high affinity receptor (FceRI) found on the surface of mast cells, basophils, and eosinophils; cross-linking of adjacent bound IgE molecules by environmental allergen leads to the release of histamine and other mediators of allergic disease [8]. IgE can bind to low affinity CD23 receptors on B cells, providing a negative regulatory signal for IgE production [7]
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