Development of a Multi-Epitope Universal mRNA Vaccine Candidate for Monkeypox, Smallpox, and Vaccinia Viruses: Design and In Silico Analyses

Abstract

Notwithstanding the presence of a smallpox vaccine that is effective against monkeypox (mpox), developing a universal vaccine candidate against monkeypox virus (MPXV) is highly required as the mpox multi-country outbreak has increased global concern. MPXV, along with variola virus (VARV) and vaccinia virus (VACV), belongs to the Orthopoxvirus genus. Due to the genetic similarity of antigens in this study, we have designed a potentially universal mRNA vaccine based on conserved epitopes that are specific to these three viruses. In order to design a potentially universal mRNA vaccine, antigens A29, A30, A35, B6, and M1 were selected. The conserved sequences among the three viral species—MPXV, VACV, and VARV—were detected, and B and T cell epitopes containing the conserved elements were used for the design of the multi-epitope mRNA construct. Immunoinformatics analyses demonstrated the stability of the vaccine construct and optimal binding to MHC molecules. Humoral and cellular immune responses were induced by immune simulation analyses. Eventually, based on in silico analysis, the universal mRNA multi-epitope vaccine candidate designed in this study may have a potential protection against MPXV, VARV, and VACV that will contribute to the advancement of prevention strategies for unpredictable pandemics.

Immunoinformatics and reverse vaccinology approach in designing a novel highly immunogenic multivalent peptide-based vaccine against the human monkeypox virus

“…Some preliminary studies have attempted and proposed few designs of such vaccine candidates based upon an approach where the construct is composed of a few epitopes for several MPX proteins, resulting in the development of dispersed immune memory. Due to limitations of scope, however, the studies lacked any investigation into the structural basis of immunogenicity of the viral proteins, upon which the reverse vaccinology computation stands (Akhtar et al, 2022;Bhattacharya et al, 2022;Jahantigh et al, 2023;Rcheulishvili et al, 2023;Waqas et al, 2023). The design presented in this article, nonetheless, relies on proteins that can exhibit high immunogenicity and activate primary innate immune cascades.…”

Evaluation and comparison of immune responses induced by two Mpox mRNA vaccine candidates in mice

“…18,[26][27][28][29][30][31] Using bioinformatics technology, we previously also designed a multiepitope universal mRNA vaccine candidate, which would have a potential protection against MPXV and contribute to the advancement of prevention strategies. 32 The MPXV mRNA vaccines currently under development varied in protective antigens selection and expression. In terms of protective antigens selection, four of them selected A29L, M1R, A35R, and B6R of MPXV (or A27L, L1R, A33R, and B5R of VACV), 26,[29][30][31] two of them included an extra E8L of MPXV on base of the mentioned four proteins, 18,28 and one even only used M1R and A35R as target antigens.…”

Dual-Target Additively Manufactured Electrochemical Sensor for the Multiplexed Detection of Protein A29 and DNA of Human Monkeypox Virus

“…Among various proteins, I1L, M1R, and A29 are highlighted. The A29 protein, in particular, stands out for being one of the most common analytes for identifying MKVP, being highly conserved among poxviruses. It is a fusion protein present on the virus envelope that binds to cell surface heparin and is a target for neutralizing antibodies. , Therefore, developing sensors specific for the A29 protein may allow direct detection of MKPV without the need for pretreatment of samples.…”

“…The A29 protein, in particular, stands out for being one of the most common analytes for identifying MKVP, being highly conserved among poxviruses. It is a fusion protein present on the virus envelope that binds to cell surface heparin and is a target for neutralizing antibodies. , Therefore, developing sensors specific for the A29 protein may allow direct detection of MKPV without the need for pretreatment of samples. Regarding the detection of genetic material, although it often requires extraction and amplification by PCR, its use is still extremely viable, being commonly applied by the main global disease control agencies (Test procedure: Monkeypox virus generic real-time PCR test).…”