Immunogenicity of a peptide‐based anti‐IgE conjugate vaccine in non‐human primates. Issue 2 (1st April 2016)

• Record Type: Journal Article
• Authors: Weeratna, Risini D.; Chikh, Ghania; Zhang, Lu; Fraser, James D.; Thorn, Jennifer M.; Merson, James R.; McCluskie, Michael J.; Champion, Brian R.; Davis, Heather L.
• Is Part Of: Immunity, inflammation and disease. Volume 4:Issue 2(2016)
• Page Start: 135
• Page End: 147
• Publication Date: 2016-04-01
• Subjects: Allergy -- anti‐IgE antibodies -- IgE -- IgE peptide conjugates -- vaccine; Immunology -- Periodicals; Immunity -- Periodicals; Inflammation -- Periodicals; 616.079
• DOI: 10.1002/iid3.98
• Languages: English
• ISSNs: 2050-4527

Abstract

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. Abstract : We developed a vaccine containing two IgE peptide‐conjugates, one which targets the same region of the human IgE Cϵ3 as omalizumab while the other targets a different region on Cϵ3. 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.