Multi-epitope mRNA Vaccine Design that Exploits Variola Virus and Monkeypox Virus Proteins for Elicitation of Long-lasting Humoral and Cellular Protection Against Severe Disease

Human monkeypox represents a relatively underexplored infection that has received increased attention since the reported outbreak in May 2022. Due to its clinical similarities with human smallpox, this virus represents a potentially tremendous health problem demanding further research in the context of host-pathogen interactions and vaccine development. Furthermore, the cross-continental spread of monkeypox has reaffirmed the need for devoting attention to human poxviruses in general, as they represent potential bioterrorism agents. Currently, smallpox vaccines are utilized in immunization efforts against monkeypox, an unsurprising fact considering their genomic and phenotypic similarities. Though it offers long-lasting protection against smallpox, its protective effects against human monkeypox continue to be explored, with encouraging results. Taking this into account, this works aims at utilizing in silico tools to identify potent peptide-based epitopes stemming from the variola virus and monkeypox virus proteomes, to devise a vaccine that would offer significant protection against smallpox and monkeypox. In theory, a vaccine that offers cross-protection against variola and monkeypox would also protect against related viruses, at least in severe clinical manifestation. Herein, we introduce a novel multi-epitope mRNA vaccine design that exploits these two viral proteomes to elicit long-lasting humoral and cellular immunity. Special consideration was taken in ensuring that the vaccine candidate elicits a Th1 immune response, correlated with protection against clinically severe disease for both viruses. Immune system simulations and physicochemical and safety analyses characterize our vaccine candidate as antigenically potent, safe, and overall stable. The protein product displays high binding affinity towards relevant immune receptors. Furthermore, the vaccine candidate is to elicit a protective, humoral and Th1-dominated cellular immune response that lasts over five years. Lastly, we build a case about the rapidity and convenience of circumventing the live attenuated vaccine platform using mRNA vaccine technology.

Abstract licence: CC BY-NC

1. 3.

   Predicting population coverage of T-cell epitope-based diagnostics and vaccines · 2006

2. 4.

   GalaxyPepDock: a protein–peptide docking tool based on interaction similarity and energy optimization · 2015

3. 12.

   Properties of MHC Class I Presented Peptides That Enhance Immunogenicity · 2013

4. 21.

   Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction · 2007

5. 30.

   ViennaRNA Package 2.0 · 2011

6. 33.

   VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines · 2007

7. 35.

   Prediction of IL4 Inducing Peptides · 2013

8. 36.

   Peptide binding predictions for HLA DR, DP and DQ molecules · 2010

9. 38.

   Designing of interferon-gamma inducing MHC class-II binders · 2013

31 more references, whose wording the paper’s licence keeps private.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.