Synthetic IgE peptide vaccine for immunotherapy of allergy

Wang, C

doi:10.1016/s0264-410x(02)00732-6

Cited by 31 publications

(35 citation statements)

References 37 publications

(49 reference statements)

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“…The following are the advantages of this novel strategy: (1) Long-lasting-it provides long-term protection with a few injections, as asthma is a chronic immunological disorder, requiring long-term treatment; (2) Low costs-the vaccine itself is less costly and the amount required to elicit immune responses will be much less in comparison to the omalizumab currently being used; (3) Less adverse reactions-as the This vaccine was shown to induce polyclonal site-specific anti-IgE antibodies that obstruct binding to FcγRI, inhibit histamine release from IgE-sensitized basophils, inhibit PCA, and do not signal degranulation. 65 Immunized dogs experienced significant reductions in total serum IgE. 65 IgE peptide-based virus-like particle vaccines.…”

Section: Discussionmentioning

confidence: 99%

“…65 IgE peptide-based virus-like particle vaccines. The antigenicity of either the chimeric IgE vaccine 64 or the IgE peptide-based vaccines 65,74 described above are not strong, requiring the addition of the strong adjuvant CFA/IFA that cannot be used in humans to elicit anti-IgE responses.…”

Section: Discussionmentioning

confidence: 99%

“…65 In the study, a human IgE peptide, modified from positions 413-435 of a loop region of Cε3, was linked to a combinatorial Th epitope derived from hepatitis B virus or later, derived from measles virus. 65 Polyclonal antibodies induced by such vaccines, which are against multiple self-antigen determinants, may cross-react with other selfproteins that contain similar epitopes. This is of particular concern when this strategy is used in humans.…”

Section: Introductionmentioning

confidence: 99%

“…Although peptide-based vaccines have been investigated by chemically coupling self-peptides to a carrier protein (keyhole limpet hemocyanin), such vaccines do not present as virus-like particles and therefore have low immunogenecity, requiring strong adjuvants (complete Freud's adjuvant) to elicit sufficient immune responses. 62,65 Recent studies have shown that the virus-like particle has unique advantages as a vaccine carrier, representing a safe and effective vaccine platform for inducing potent B and T cell responses. Virus-like particles have been used previously to induce auto-antibodies to disease-associated self molecules involved in chronic diseases.…”

Section: Introductionmentioning

confidence: 99%

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Vaccines targeting IgE in the treatment of asthma and allergy

Peng

2009

Human Vaccines

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inappropriate immune responses characterized by the increase of serum IgE antibodies to common aeroallergens in genetically susceptible individuals.Serum IgE levels have been correlated with airway hyperresponsiveness both in adults 10,11 and in children, 12 and is associated with the severity of asthma. 13 It is well-established that the risk of developing asthma increases with increasing levels of serum IgE. 11 In addition to asthma, IgE is also responsible for allergic rhinitis, atopic dermatitis, adverse reactions to foods, medications, insect bites and stings and anaphylaxis, which are also increasing at an alarming rate. 3,5,14 Immunotherapies and biological agents in the treatment of asthma and allergy. Basic treatment for allergy and asthma includes (1) allergen avoidance, (2) pharmacological management that consists of sodium cromoglycate, inhaled corticosteroids, and histamine H1-receptor antagonists, etc. and (3) immunotherapy consisting of antigen-specific and non-allergen-specific approaches. 15 The purpose of antigen-specific immunotherapy is to desensitize allergic subjects by repeated subcutaneous injections of small and gradually increasing amounts of the offending allergen. This therapy has been used for more than 100 years and is effective in the treatment of hay fever and venom allergy, but is less effective in asthma control. 15 As most allergic subjects are sensitized to multiple allergens, non-allergen specific immunotherapy would be more effective in the treatment of these subjects. Overexpressed IgE and Th2 cytokines play important roles in the development of allergic inflammation; one intriguing strategy aims at limiting production of IgE and cytokines, or their accessibility to their respective receptors, so as to control the pathogenic process. To date, many new biological agents used as therapeutic modifiers have emerged as important new treatments. These include the administration of humanized monoclonal antibodies (mAbs) against such molecules or their receptors, soluble receptors, or mutated cytokines as passive blockers, [16][17][18][19] as summarised in Table 1. 16,20 Among these biological agents, the monoclonal antibody to IgE (omalizumab) has been proven to be effective in the treatment of asthma.IgE and its high affinity receptor (FcγRI). Since IgE was discovered in 1966, 21 it has been considered to be an important biological target in the treatment of allergy and asthma. IgE antibodies are known to play a major role in the development and regulation of asthmatic responses and are directly responsible for the allergic cascade. 22 These allergen-specific IgE antibodies bind to high affinity Allergic diseases including asthma are characterized by an increase of serum IgE levels. Since IgE was discovered in 1966, it has been considered to be the most important biological target in the treatment of allergy and asthma. Indeed, recent studies reveal that IgE, through its high affinity IgE receptors (FcεRI), is now considered a critical regulator of Th2 responses. This is suppor...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Vaccines targeting IgE in the treatment of asthma and allergy

Peng

2009

Human Vaccines

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“…É o caso do sarampo 90 , da malária 91 , da infecção causada pelo vírus sincitial respiratório humano 92 e de melanoma 93 . Os sintéticos empregados como candidatos potenciais de vacinas geralmente correspondem a fragmentos derivados de epitopos de proteínas antigênicas específicas 94 , a peptídeos que induzem resposta imune in vitro e in vivo frente a carboidratos ou, ainda, a peptídeos ramificados compostos de um esqueleto de lisinas ou de β-Ala-Lys, em cujos grupos ε-amino se ligam fragmentos de epitopos de proteínas antigênicas específicas (MAPs -"multiple antigenic peptide") 95 .…”

Section: Imunologiaunclassified

Sínteses química e enzimática de peptídeos: princípios básicos e aplicações

Machado¹,

Liria²,

Proti³

et al. 2004

Quím. Nova

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Recebido em 17/9/03; aceito em 27/11/03; publicado na web em 17/6/04 CHEMICAL AND ENZYMATIC PEPTIDE SYNTHESES: BASIC ASPECTS AND APPLICATIONS. This review begins with a brief discussion of the biological importance and chemical features of peptides. A description of the existing synthetic methods follows with emphasis on the basic aspects of the chemical and enzymatic syntheses. Techniques used to purify and characterize the synthesized peptides are also discussed. Finally, a few applications of the final products in chemistry, biochemistry, immunology and medicine are presented, such as identification and quantification of naturally occurring peptides, inspection of structureactivity relationships, therapeutics, development and/or improvement of analytical techniques and search for new vaccines.Keywords: peptides; synthesis; applications of synthetic peptides. A DIVERSIDADE FUNCIONAL E QUÍMICA DOS PEPTÍDEOSOs peptídeos são biomoléculas que contém de dois a dezenas de resíduos de aminoácidos unidos entre si através de ligações peptídicas. Se comparados às proteínas, são quimicamente mais versáteis, pois podem ser amidados ou esterificados em suas carboxilas terminais, acetilados em seus grupos amino terminais, fosforilados ou sulfatados em um ou mais resíduos (serina, treonina ou tirosina), lineares, semicíclicos (geralmente via uma ou mais ligações dissulfeto intra-ou intercadeias peptídicas) ou cíclicos (via ligação entre os grupos amino e carboxila dos aminoácidos terminais). Muitos contêm um ácido piroglutâmico como resíduo N-terminal, outros apresentam Daminoácidos e outros, ainda, possuem aminoácidos não usuais 1 . Os peptídeos são também extremamente diversificados em termos funcionais. Muitos atuam como hormônios ou fatores liberadores destes, enquanto outros são neuropeptídeos, neurotransmissores, toxinas, antibióticos naturais, adoçantes ou substratos de proteases. Na verdade, vários deles fazem parte de nossas conversas sem que nos apercebamos disto: é o caso do aspartame, da insulina, da ocitocina e de diversas drogas comerciais, que consistem em antagonistas de peptídeos naturais ou em inibidores de enzimas envolvidas na sua produção e liberação no organismo 2-4 . A Tabela 1 fornece alguns exemplos desta diversidade funcional e química. Todo este conhecimento começou a ser acumulado principalmente a partir da década de 50, quando vários peptídeos ativos foram descobertos e tiveram as suas estruturas químicas determinadas. Foi o caso de diversos hormônios que controlam o metabolismo animal (glucagon e insulina, p.ex.) e de outros que desempenham papéis específicos em nosso organismo (ocitocina, vasopressina e o hormônio estimulador de melanócitos, p. ex.) 10 . Estas descobertas geraram um enorme interesse por esta classe de compostos e por metodologias para seu isolamento, análise, purificação, identificação e quantificação, as quais passaram a ser sistematicamente estudadas e aprimoradas. Em paralelo, deparou-se com a necessidade de sintetizar estas moléculas e análogos (derivados com modificações p...

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Immunogenicity of a peptide‐based anti‐IgE conjugate vaccine in non‐human primates

Weeratna

Chikh

Zhang

et al. 2016

Immunity Inflam & Disease

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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.

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Synthetic IgE peptide vaccine for immunotherapy of allergy

Cited by 31 publications

References 37 publications

Vaccines targeting IgE in the treatment of asthma and allergy

Vaccines targeting IgE in the treatment of asthma and allergy

Sínteses química e enzimática de peptídeos: princípios básicos e aplicações

Immunogenicity of a peptide‐based anti‐IgE conjugate vaccine in non‐human primates

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