Vaccine against peanut allergy based on engineered Virus-Like-Particles displaying single major peanut allergens.

Storni, Federico; Zeltins, Andris; Balke, Ina; Heath, Matthew D; Kramer, Matthias F; Skinner, Murray A; Zha, Lisha; Rösti, Elisa; Engeroff, Paul; Muri, Lukas; von Werdt, Diego; Gruber, Thomas; Cragg, Mark; Mlynarczyk, Margrit; Kündig, Thomas M; Vogel, Monique; Bachmann, Martin (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. Elsevier 10.1016/j.jaci.2019.12.007

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BACKGROUND

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

OBJECTIVE

We aimed to develop an immunogenic, protective and non-reactogenic 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 one 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 i.v. 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.

CONCLUSION

Our data suggest that vaccination using single peanut allergens displayed on CuMVtt may represent a novel and safe therapy against peanut allergy.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Service Sector > Institute of Pathology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Storni, Federico Lorenzo; Rösti, Elisa Simona; Engeroff, Paul Simon; Muri, Lukas Kilian; von Werdt, Diego; Gruber, Thomas; Vogel, Monique and Bachmann, Martin

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

1097-6825

Publisher:

Elsevier

Language:

English

Submitter:

Lee-Anne Brand

Date Deposited:

14 Jan 2020 09:19

Last Modified:

20 Dec 2020 02:30

Publisher DOI:

10.1016/j.jaci.2019.12.007

PubMed ID:

31866435

Uncontrolled Keywords:

Virus-Like Particles food allergy novel therapy safe vaccination

BORIS DOI:

10.7892/boris.137753

URI:

https://boris.unibe.ch/id/eprint/137753

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