Development of a novel multi-epitope mRNA vaccine candidate to combat HMPV virus

ABSTRACT

Human metapneumovirus (HMPV) is one of the main pathogens causing severe respiratory infections in children, as a common cause of immunodeficiency-related deaths in children and elderly individuals, the prevalence of HMPV has been showing an increasing trend during the last years. However, no vaccines or effective treatment plans are available currently. In this present, based on candidate proteins highly associated with viral virulence and has promising protective potential, we screened for immunodominant cytotoxic T cells, helper T cells, and Linear B-cell epitopes from the most promising candidate Fusion protein, together with G, SH, M, and M2. All epitopes were predicted to have strong antigenicity by Vaxijen and pose no potential toxicity, allergenicity, or hormonology to human proteins by Toxinpred, Allerpred, and Blast analysis, meanwhile, high conservancy is demanded to cover different subtypes. adjuvants β-defensin II and Pam2Cys was attached with EAAAK linkers to improve vaccine’s efficiency. Then, calculation of physicochemical properties proved the protein vaccine as a product can stably exist in the human body. Besides, we assessed the docking between the vaccine and immune receptors to evaluate its ability to stimulate immune responses, and the dynamic simulation further confirmed that the vaccine can tightly bind with immune receptors, which approved that the construction has the potential to induce strong humoral and cellular immune response. Finally, the vaccine was constructed into a multi-epitope mRNA vaccine, the immune simulations suggest that this is a vaccine candidate for controlling HMPV infection.

KEYWORDS:

• HMPV
• fusion protein
• epitope docking
• molecular dynamics
• multi-epitope vaccine
• mRNA vaccine

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Acknowledgments

Thanks to the support from HY.W, C.Z, and L.Z.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Conceptualization, F.Z, and S.M.; methodology, F.Z.; validation, S.M. and Y.X., and M.R.; formal analysis, P.Z, W.P, H.Y and Y.C; writing – original draft preparation, S.M, Y.X and C.T; writing – review and editing:J.C; supervision, P.P and J.C.; project administration, P.P and J.C; funding acquisition, P.P

Data available statement

The data that support the findings of this study are available from the corresponding author, Pinhua Pan, upon reasonable request.

Declaration of generative AI in scientific writing

No AI technology is used in scientific writing.

Submission declaration and verification

This article has not been published previously, and it is not under consideration for publication elsewhere, its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2023.2293300.

Additional information

Funding

This work is supported by the National Natural Science Foundation of China [No. 81770080]; Project Program of National Clinical Research Center for Geriatric Disorders [Xiang ya Hospital,Grant No. 2020LNJJ05]; The National Natural Science Foundation of China [No. 8210012334]; National Key R&D Program of China [No. 2016YFC1304204]; Key R&D Program of Hunan Province [No. 2022SK2038]; Project Program of central south university graduate education teaching reform [No. 2022JGB025]; The national key clinical specialist construction programs of China [Grant Number z047-02]; Research Project of Teaching Reform in Colleges and Universities in Hunan Province [2021jy139-2]; China Postdoctoral Science Foundation [2022M713520]; Project on the topic of emergency response to combat the COVID-19 epidemic in Hunan Province [2022SK2122]; Research Project on teaching reform of ordinary colleges and universities in Hunan province [2022JGYB037].