title: Immunogenicity of a peptide-based anti-IgE conjugate vaccine in non-human primates.
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.
authors.affiliation: Pfizer Vaccine Immunotherapeutics Ottawa Laboratories Ottawa Ontario Canada.
authors.forename: Risini D
authors.initials: RD
authors.lastname: Weeratna
authors.affiliation: Pfizer Vaccine Immunotherapeutics Ottawa Laboratories Ottawa Ontario Canada.
authors.forename: Ghania
authors.initials: G
authors.lastname: Chikh
authors.affiliation: Pfizer Vaccine Immunotherapeutics Ottawa Laboratories Ottawa Ontario Canada.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Pfizer Vaccine Immunotherapeutics La Jolla California USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Fraser
authors.affiliation: Pfizer Biotherapeutics Pharmaceutical Sciences St. Louis Missouri USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Thorn
authors.affiliation: Pfizer Biotherapeutics Pharmaceutical Sciences St. Louis Missouri USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Merson
authors.affiliation: Pfizer Vaccine Immunotherapeutics Ottawa Laboratories Ottawa Ontario Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McCluskie
authors.affiliation: Pfizer Vaccine Immunotherapeutics La Jolla California USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Champion
authors.affiliation: Pfizer Vaccine Immunotherapeutics Ottawa Laboratories Ottawa Ontario Canada.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Davis
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001249:Asthma / Q000628:therapy; D006801:Humans; D000069444:Omalizumab; D011323:Primates; D014581:Urticaria / Q000628:therapy; D018074:Vaccines, Conjugate / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018074:Vaccines, Conjugate; C026408:anti-IgE antibodies; D000069444:Omalizumab
keywords: Allergy; IgE; IgE peptide conjugates; anti‐IgE antibodies; vaccine