Development of a peptide conjugate vaccine for inducing therapeutic anti-IgE antibodies

ABSTRACT

Introduction: Given the multifaceted effector functions of IgE in immediate hypersensitivity, late-phase reactions, regulation of IgE receptor expression and immune modulation, IgE antibodies have long represented an attractive target for therapeutic agents in asthma and other allergic diseases. Effective pharmacologic blockade of the binding of IgE to its receptors has become one of most innovative therapeutic strategies in the field of allergic diseases in the last 10 years.

Areas covered: The latest strategies targeting IgE include the development of a therapeutic vaccine, able to trigger our own immune systems to produce therapeutic anti-IgE antibodies, potentially providing a further step forward in the treatment of allergic diseases. The aim of this review is to discuss the discovery strategy, preclinical and early clinical development of a peptide conjugate vaccine for inducing therapeutic anti-IgE antibodies.

Expert opinion: Outside the area of development of humanized anti-IgE monoclonal antibodies, the research field of therapeutic IgE-targeted vaccines holds potential benefits for the treatment of allergic diseases. However, most of the experimental observations in animal models have not yet been translated into new treatments and evidence of human efficacy and safety of this new therapeutic strategy are still lacking.

KEYWORDS:

• IgE
• anti-IgE
• omalizumab
• vaccine
• virus-like particles
• adjuvants
• allergy
• asthma

Article highlights

• In addition to mediating the classic immediate hypersensitivity reactions by inducing acute mediator release by mast cells, IgE has a number of immunomodulatory functions. Thus, IgE has become a major therapeutic target for allergic diseases.

• Omalizumab, the unique currently approved IgE-specific IgG1 mAb, is a validated therapeutic tool both in adults and children, in particular for the treatment of uncontrolled allergic asthma. Current limitations of omalizumab therapy are mainly problems of high cost and patients’ adherence to treatment.

• Novel investigational anti-IgE monoclonal antibodies with improved pharmacodynamic properties are in the pipeline, potentially offering alternative mechanisms of modulating IgE pathway.

• The latest strategies targeting IgE include the development of a therapeutic vaccine, able to trigger our own immune systems to produce therapeutic anti-IgE antibodies.

• A therapeutic anti-IgE vaccine may offer long-term efficacy reducing costs, increasing patients’ compliance and safety and potentially modifying the course of the allergic diseases in comparison with current available biological therapy.

• To date, evidence of efficacy and safety of an anti-IgE vaccine are limited to preclinical studies, and most of the experimental observations in animal models have not yet been translated into new treatments.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This manuscript has not been funded.