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.
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