Vaccine against peanut allergy based on engineered virus-like particles displaying single major peanut allergens.

Abstract

BACKGROUND:

Peanut allergy is a severe and increasingly frequent disease with high medical, psychosocial, and economic burden for affected patients and wider society. A causal, safe, and effective therapy is not yet available.

OBJECTIVE:

We sought to develop an immunogenic, protective, and nonreactogenic vaccine candidate against peanut allergy based on virus-like particles (VLPs) coupled to single peanut allergens.

METHODS:

To generate vaccine candidates, extracts of roasted peanut (Ara R) or the single allergens Ara h 1 or Ara h 2 were coupled to immunologically optimized Cucumber Mosaic Virus-derived VLPs (CuMVtt). BALB/c mice were sensitized intraperitoneally with peanut extract absorbed to alum. Immunotherapy consisted of a single subcutaneous injection of CuMVtt coupled to Ara R, Ara h 1, or Ara h 2.

RESULTS:

The vaccines CuMVtt-Ara R, CuMVtt-Ara h 1, and CuMVtt-Ara h 2 protected peanut-sensitized mice against anaphylaxis after intravenous challenge with the whole peanut extract. Vaccines did not cause allergic reactions in sensitized mice. CuMVtt-Ara h 1 was able to induce specific IgG antibodies, diminished local reactions after skin prick tests, and reduced the infiltration of the gastrointestinal tract by eosinophils and mast cells after oral challenge with peanut. The ability of CuMVtt-Ara h 1 to protect against challenge with the whole extract was mediated by IgG, as shown via passive IgG transfer. FcγRIIb was required for protection, indicating that immune complexes with single allergens were able to block the allergic response against the whole extract, consisting of a complex allergen mixture.

CONCLUSIONS:

Our data suggest that vaccination using single peanut allergens displayed on CuMVtt may represent a novel therapy against peanut allergy with a favorable safety profile.

• Authors: Federico Storni, Andris Zeltins, Ina Balke, Matthew D Heath, Matthias F Kramer, Murray A Skinner, Lisha Zha, Elisa Roesti, Paul Engeroff, Lukas Muri, Diego von Werdt, Thomas Gruber, Mark Cragg, Malgorzata Mlynarczyk, Thomas M Kündig, Monique Vogel, Martin F Bachmann
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 145 Issue 4 Pg. 1240-1253.e3 (04 2020) ISSN: 1097-6825 [Electronic] United States
• PMID: 31866435 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antigens, Plant
• Ara h 1 protein, Arachis hypogaea
• FCGR2B protein, human
• Immunodominant Epitopes
• Membrane Proteins
• Plant Proteins
• Receptors, IgG
• Vaccines
• Immunoglobulin E

Topics

• Animals
• Antigens, Plant (genetics, immunology)
• Arachis (genetics)
• Cucumovirus (genetics)
• Desensitization, Immunologic (methods)
• Genetic Engineering
• Humans
• Immunodominant Epitopes (immunology)
• Immunoglobulin E (metabolism)
• Membrane Proteins (genetics, immunology)
• Mice
• Mice, Inbred BALB C
• Peanut Hypersensitivity (therapy)
• Plant Proteins (genetics, immunology)
• Receptors, IgG (metabolism)
• Vaccines (genetics, immunology)
• Virion (genetics, immunology)