Designing a next-generation self-amplifying mRNA vaccine against Hepatitis E Virus 1 (HEV-1): A reverse vaccinology and immunoinformatics approach

Abstract Hepatitis E virus 1 (HEV-1) is a worldwide public health issue that induces acute viral hepatitis as well as high mortality, especially among pregnant women and immunocompromised subjects. The World Health Organization has characterized Hepatitis E virus as an emerging pathogen for a vaccine design that has become most important for its elimination. Currently, there is only one available vaccine for hepatitis E that is exclusively administered in China. Another potential vaccine, the recombinant Hepatitis E virus vaccine, has not yet been approved for commercial use. Bioinformatics methods have shown potential for the development of vaccine candidates, particularly Hepatitis E virus. mRNA technology has received great interest because it can induce both B and T cell immune responses, is safe, and is a cell-free manufacturing process. Self-amplifying RNA-based vaccines, which code for the antigen of interest as well as proteins enabling the duplication of RNA, result in enhanced antigen expression as well as equivalent immune responses to those of mRNA-based vaccines. This study seeks to design a novel self-amplifying mRNA anti-HEV vaccine using immunoinformatic tools based on the ORF2 antigen. We predicted antigenic, non-toxic, and non-allergic epitopes of B and T cells and assembled the selected epitopes with appropriate linkers for mRNA vaccine construction. Bioinformatics data, including physicochemical properties, 2D, 3D structural modeling, validation and refinement analyzes, and mRNA secondary structure, illustrated the stability and quality of the designed vaccine. Molecular docking and simulation indicated effectively engaging the immune system and eliciting a strong immune response by TLR4. Immune simulations demonstrate a robust initial immune response, with a gradual increase in levels of immunoglobulins, cytokines, cytotoxic T cells, and helper T cell populations following a single dose administration. However, this in silico study presents a promising self-amplifying mRNA vaccine candidate against HEV, which requires further evaluation and validation through additional tests, such as preclinical and clinical trials.