Development of a novel circular mRNA vaccine of six protein combinations against Staphylococcus aureus

Abstract

Staphylococcus aureus is an extraordinarily versatile pathogen, which is currently the most common cause of nosocomial and community infections. Considering that increased antibiotic resistance may hasten the spread of S. aureus, developing an effective vaccine can possibly aid in its control. The RNA vaccine coding immunodominance epitopes from bacteria provide a potential method to induce T and B cell immune responses by translating them into cells. Furthermore, using bioinformatics to create circular RNA vaccines can ensure that the translation of the vaccine is potent and durable. In this study, 7 cytotoxic T lymphocyte (CTL) epitopes, 4 helper T lymphocyte (HTL) epitopes, and 15 B cell epitopes from 6 proteins that are closely associated with the S. aureus virulence and invasion and critical to natural immune responses were mapped. To verify their interactions, all epitopes were docked with the corresponding MHC alleles. The final vaccine was composed of 26 epitopes and the adjuvant β-defencin, and a disulfide bond was also introduced to improve its stability. After the prediction of structure and characteristics, the developed vaccine was docked with TLR2 and TLR4, which induce immunological responses in S. aureus infection. According to the molecular dynamic simulation, the vaccine might interact strongly with TLRs. Meanwhile, it performed well in immunological simulation and population coverage prediction. Finally, the vaccine was converted into a circular RNA using a series of helper sequences to aid in vaccine circulation translation. Hopefully, this proposed structure will be proven to serve a viable vaccine against S. aureus.

Communicated by Ramaswamy H. Sarma

Keywords:

• S. aureus
• circular RNA vaccine
• epitope vaccine
• epitope docking
• molecular dynamics
• multi-epitope vaccine

Author contributions

Conceptualization, F.Z, and S.M.; methodology, F.Z.; validation, S.M., and M.R.; formal analysis, P.Z, W.P, H.Y and Y.C; writing—original draft preparation, S.M, 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.

Acknowledgments

The author thank his classmate Cheng Zhao for his guidance in bioinformatics. The authors thank Mr. Sean Liu from QS Translation for his English language proofreading service.

Data availability statement

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

Disclosure statement

No potential conflict of interest was reported by the authors.

Geolocation information

Changsha, Hunan province of China

Additional information

Funding

This work is supported by 1. The National Natural Science Foundation of China (No. 81770080). 2. Supported by the Project Program of National Clinical Research Center for Geriatric Disorders (Xiang ya Hospital, Grant No. 2020LNJJ05). 3. The National Natural Science Foundation of China (No. 8210012334). 4. National Key R&D Program of China (No. 2016YFC1304204) 5. The national key clinical specialist construction programs of China (Grant Number z047-02). 6. Research Project on Education and Teaching Reform of Central South University No.2021iy139-2.