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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:41

Enthalten in:

Journal of biomolecular structure & dynamics - 41(2023), 20 vom: 17. Dez., Seite 10525-10545

Sprache:

Englisch

Beteiligte Personen:

Zhu, Fei [VerfasserIn]
Ma, Shiyang [VerfasserIn]
Wen, Haicheng [VerfasserIn]
Rao, Mingjun [VerfasserIn]
Zhang, Peipei [VerfasserIn]
Peng, Wenzhong [VerfasserIn]
Cui, Yanhui [VerfasserIn]
Yang, Hang [VerfasserIn]
Tan, Caixia [VerfasserIn]
Chen, Jie [VerfasserIn]
Pan, Pinhua [VerfasserIn]

Links:

Volltext

Themen:

Circular RNA vaccine
Epitope docking
Epitope vaccine
Epitopes, B-Lymphocyte
Epitopes, T-Lymphocyte
Journal Article
Molecular dynamics
Multi-epitope vaccine
RNA, Circular
Research Support, Non-U.S. Gov't
S. aureus
Vaccines, Subunit

Anmerkungen:

Date Completed 10.11.2023

Date Revised 13.11.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1080/07391102.2022.2154846

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM350452156