D2.153 - Allergenicity and Immunogenicity of Polypeptide-Conjugated Hepatitis B Core Antigen Virus‐Like-Particle (HBcAg-VLP) Vaccine for Treatment of Shellfish Allergy

The escalating prevalence of shellfish allergy is a public health concern, with allergen-specific immunotherapy (AIT) being the main curative treatment for such food allergy. Oral immunotherapy (OIT) practiced clinically over the past few decades shows high rates of desensitization. However, challenges associated with OIT, including low rates of sustained efficacy, poor compliance, and high risk of adverse reactions have underscored the urgency for novel AIT approaches. Hence, this study leverages next-generation AIT strategies by developing a nanoparticle-based recombinant protein vaccine to treat shellfish allergy. It is hypothesized that immunization of virus-like particles (VLPs) as an immunogenic carrier for the polypeptides derived from the major shellfish allergen, tropomyosin (TM), can confer protection against shellfish allergy.

The vaccine was constructed via a plug-and-display platform, where a polypeptide derived from shrimp TM, Metapenaeus ensis 1 (Met e 1) allergen, was displayed on the surface of Hepatitis B Virus Core Antigen (HBcAg) VLPs using SpyTag/SpyCatcher technology. Then, 2µg of the vaccine, along with AddaVax as adjuvant, was subcutaneously administered into 5-week-old female naïve BALB/c mice following a prime-boost-boost regimen on day 0, 14 and 31. The mice were monitored for up to day 90, with serum samples collected at specific timepoints for antibody analyses.

Met e 1-derived polypeptide was found to be hypoallergenic with lower binding affinity than full-length Met e 1 allergen towards specific IgE of TM-allergic patient. The HBcAg-VLP synthesized in-house was successfully conjugated with Met e 1-derived polypeptide through simply mixing under optimized conditions. After the second immunization, Met e 1-specific IgG antibody was induced on day 21 in naïve mice. The antibody titre was significantly increased after the third immunization to a level that was comparable to immunization with free Met e 1 allergen with AddaVax, and the effect was sustained up to day 90.

Current findings have validated the robust synthesis of polypeptide-conjugated HBcAg-VLP vaccine with low allergenicity and high immunogenicity profiles. Future work may involve determining the minimal effective dosage of vaccine, and investigating the subtypes of sIgG induced postvaccination. These results have paved the way for future studies on the vaccine’s therapeutic efficacy against shellfish allergy. (funded by CUHK Direct Grants 4054775 and 4054881)