Designing Next-Generation Vaccines Against Common Pan-Allergens Using In Silico Approaches.

Abstract

Next-generation allergy vaccines refer to allergen-derived attenuated molecules that can boost allergen-blocking IgG response. These IgG antibodies are specifically directed toward the IgE epitope of allergens and interfere in allergen-IgE interaction. Our study is a computational approach to design such vaccines against four widespread pan-allergens families. Pan-allergens display extensive immunological cross-reactivity due to the presence of conserved IgE epitope and T cell epitope. In this study, the vaccine design is based on hapten-carrier concept in which the carrier protein is an immunogenic component providing T cell help. Either PreS protein of hepatitis B or cholera enterotoxin B (CTB) fused with three tetanus toxoid fragments (TTFrC) was used here as the carrier. The hapten components are nonanaphylactic peptides (NAPs) derived from experimentally determined antigenic regions of the allergens. The charged residues of NAPs are selectively modified to obliterate IgE, as well as T cell reaction, and hence, are safe to apply in allergy patients. Various combinations of vaccine constructs (PreS/CTB+TTFrC and NAPs) were designed with intermediate linker motifs. Screening of constructs was performed through a three-step method such as physicochemical parameters, secondary structures, and tertiary structures using various bioinformatic tools. The final construct with best quality and stability was selected for each allergen family. Suitability of these constructs for being expressed in recombinant form was checked at DNA, RNA, and protein level. Presence of putative epitopes inducing tolerogenic interleukin-10 was also predicted for these constructs. The present work led to the design of putative vaccines with immunotherapeutic potential and broad applicability for allergic diseases caused by a wide array of cross-reactive allergens.