Details

While the world is threatened by the COVID-19 pandemic from the SARS-CoV-2 virus, the outbreak of the monkeypox virus (MPXV) has been reported to the WHO on May 7, 2022. According to reports from the World Health Organization (WHO), there are 138,991 MPXV infections worldwide and 649 deaths from this infection. There is an urgent need to develop effective vaccines to prevent the spread of MPXV. Currently, traditional vaccine development relies mainly on live attenuated vaccines, which are low throughput, expensive, time-consuming, and can revert to virulence. As an alternative to live attenuated vaccines, subunit vaccines have been demonstrated as a viable option for vaccine due to lower side-effects, high safety, and reproducibility. In this research, various proteins associated with MPXV infection, including F8L, C2L, A40L, H3L, B6R, B9R, and E4R, were analyzed for potential immunogenic epitopes to design multi-epitope vaccine constructs based on B-cell, CD4+, and CD8+ epitopes. These epitopes were further refined based on allergenicity, antigenicity, autoimmune induction, and toxicity parameters. Prioritized epitopes were then combined via peptide linkers, and N-terminally fused to different adjuvants, and thus yielding 5 vaccine constructs. All vaccine constructs were further computationally evaluated for physicochemical properties, antigenicity potential, allergenicity, safety, solubility, and structural stability. Moreover, molecular docking simulation between vaccine and viral protein sensing TLR-1, TLR-2, TLR-4, TLR-6, and TLR-10 immune receptor was evaluate for its binding efficiency, and the studies demonstrated a strong and stable interaction between vaccine and all TLRs. In line with molecular docking simulation, molecular dynamics simulation has further substantiated the strong binding stability of our vaccine constructs with TLRs. The analyses of the immune simulation indicated that our vaccines could effectively induce both humoral and cell-mediated immune response  in the human body. The vaccine constructs were codon-optimized for high expression in E. coli platform and was finally in silico cloned into pET21a (+) vector. Collectively, these results could be a representative for innovative tools for vaccine formulation against MPXV and could be transformative to other types of diseases.

Objective

The monkeypox outbreak has caused serious concern. It may be transmitted through imported animals or airborne particles, causing widespread outbreaks. Multi-epitope vaccines are important to effectively control the spread of this disease. A multi-epitope vaccine involves the joining of several epitopes together and adding adjuvants and linkers to enhance the efficiency of the vaccine. And there is a check on the safety of the vaccine, such as being an antigen. It does not cause allergies, is not toxic to humans using computer analysis to ensure that there will be no side effects after vaccination, and also has the ability to prevent the spread of MPXV infection on a wide scale.

Project Members

ภาณุวิชญ์ จุมปาลี

PANUWID JUMPALEE

#นักศึกษา

Member

พนา โลหะทรัพย์ทวี

Pana Lohasupthawee

#อาจารย์

Advisor

บุญฤทธิ์ เมฆศิริพร

#อาจารย์

Co-advisor

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