Monkeypox (mpox) is a zoonotic infectious disease caused by the mpox virus. Mpox symptoms are similar to smallpox with less severity and lower mortality. As yet mpox virus is not characterized by as high transmissibility as some severe acute respiratory syndrome 2 (SARS-CoV-2) variants, still, it is spreading, especially among men who have sex with men (MSM). Thus, taking preventive measures, such as vaccination, is highly recommended. While the smallpox vaccine has demonstrated considerable efficacy against the mpox virus due to the antigenic similarities, the development of a universal anti-mpox vaccine remains a necessary pursuit. Recently, nucleic acid vaccines have garnered special attention owing to their numerous advantages compared to traditional vaccines. Importantly, DNA vaccines have certain advantages over mRNA vaccines. In this study, a potentially universal DNA vaccine candidate against mpox based on conserved epitopes was designed and its efficacy was evaluated via an immunoinformatics approach. The vaccine candidate demonstrated potent humoral and cellular immune responses in silico, indicating the potential efficacy in vivo and the need for further research.
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.
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