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

Vaccine against peanut allergy based on engineered virus-like particles displaying single major peanut allergens
Vaccine against peanut allergy based on engineered virus-like particles displaying single major peanut allergens
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.
Food allergy, novel therapy, virus-like particles
0091-6749
1240-1253.e3
Storni, Federico
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Zeltins, Andris
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Balke, Ina
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Heath, Matthew D.
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Kramer, Matthias F.
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Skinner, Murray A.
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Zha, Lisha
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Roesti, Elisa
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Engeroff, Paul
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Muri, Lukas
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Von Werdt, Diego
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Gruber, Thomas
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Cragg, Mark
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Mlynarczyk, Malgorzata
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Kündig, Thomas M.
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Vogel, Monique
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Bachmann, Martin F.
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Storni, Federico
0ce465fa-a1d8-4225-8240-72ec54ecb797
Zeltins, Andris
aaae10f0-58a4-4bee-bba1-d6444cd268d8
Balke, Ina
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Heath, Matthew D.
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Kramer, Matthias F.
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Skinner, Murray A.
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Zha, Lisha
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Roesti, Elisa
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Engeroff, Paul
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Muri, Lukas
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Von Werdt, Diego
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Gruber, Thomas
ae18a432-0e89-42f0-b61f-a7d2c90bf39c
Cragg, Mark
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Mlynarczyk, Malgorzata
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Kündig, Thomas M.
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Vogel, Monique
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Bachmann, Martin F.
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Storni, Federico, Zeltins, Andris, Balke, Ina, Heath, Matthew D., Kramer, Matthias F., Skinner, Murray A., Zha, Lisha, Roesti, Elisa, Engeroff, Paul, Muri, Lukas, Von Werdt, Diego, Gruber, Thomas, Cragg, Mark, Mlynarczyk, Malgorzata, Kündig, Thomas M., Vogel, Monique and Bachmann, Martin F. (2020) Vaccine against peanut allergy based on engineered virus-like particles displaying single major peanut allergens. Journal of Allergy and Clinical Immunology, 145 (4), 1240-1253.e3. (doi:10.1016/j.jaci.2019.12.007).

Record type: Article

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.

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More information

Accepted/In Press date: 10 December 2019
e-pub ahead of print date: 19 December 2019
Published date: April 2020
Keywords: Food allergy, novel therapy, virus-like particles

Identifiers

Local EPrints ID: 437644
URI: http://eprints.soton.ac.uk/id/eprint/437644
ISSN: 0091-6749
PURE UUID: 8ddf8526-4f53-4a1d-8b31-7dd921543015
ORCID for Mark Cragg: ORCID iD orcid.org/0000-0003-2077-089X

Catalogue record

Date deposited: 07 Feb 2020 17:32
Last modified: 26 Nov 2021 07:16

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Contributors

Author: Federico Storni
Author: Andris Zeltins
Author: Ina Balke
Author: Matthew D. Heath
Author: Matthias F. Kramer
Author: Murray A. Skinner
Author: Lisha Zha
Author: Elisa Roesti
Author: Paul Engeroff
Author: Lukas Muri
Author: Diego Von Werdt
Author: Thomas Gruber
Author: Mark Cragg ORCID iD
Author: Malgorzata Mlynarczyk
Author: Thomas M. Kündig
Author: Monique Vogel
Author: Martin F. Bachmann

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