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. FcgRIIb 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. (J

Development of a vaccine against the newly emerging COVID-19 virus based on the receptor binding domain displayed on virus-like particles

“…Furthermore, the CuMVTT based vaccine is based on highly efficient expression systems and chemical conjugation technologies, rendering it an attractive candidate for large scale production under cGMP. Previous studies with a similar VLP-based conjugate vaccine has demonstrated that high levels of specific antibodies can be mounted within a week 13,14 (see also Fig. 2a), offering the additional possibilities to rapidly immunize individuals that have been exposed to infected humans or those that are kept in quarantine.…”

Recent Advances in the Use of Plant Virus-Like Particles as Vaccines

“…The resulting vaccines did not cause allergic reactions and induced specific IgG antibodies to protect peanut-sensitized mice against anaphylactic shock. Notably, immunizations with single allergen-containing VLPs ensured protection against challenge with the complex allergen mixture, suggesting a new vaccination strategy for the treatment of peanut allergy [78]. Other examples of VLP usage in the treatment of allergic diseases are summarized in a recently published review article [79].…”

Molecular approaches to allergen‐specific immunotherapy: Are we so far from clinical implementation?

“…Moreover, VLP‐Der p 2 triggered strong allergen‐specific blocking IgG and prevented the development of the HDM‐allergic response in mice . Promising preclinical efficacy data were produced as well with VLP displaying peanut allergen Ara h 1 or Ara h 2 . The protective effect of these two molecules was also mediated by the IgG production.…”