Infectious disease mRNA vaccines and a review on epitope prediction for vaccine design

Cai, Xinhui; Li, Jiao Jiao; Liu, Tao; Oliver, Brian G.; Li, Jinyan

doi:10.1093/bfgp/elab027

Cited by 21 publications

(16 citation statements)

References 83 publications

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“…Moreover, mRNA vaccines are more appropriate for targeting diseases via high genetic instability and infectivity than other vaccines. mRNA-based vaccines were first used as a therapeutic drug in 1989 [ 186 , 187 ]. It has been proven that the encapsulation of mRNA in LNP facilitates the control of biodistribution as well as cell targeting.…”

Section: Pharmacological Study Of Mrna-lnp Deliverymentioning

confidence: 99%

Recent advances in mRNA-LNP therapeutics: immunological and pharmacological aspects

et al. 2022

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In the last decade, the development of messenger RNA (mRNA) therapeutics by lipid nanoparticles (LNP) leads to facilitate clinical trial recruitment, which improves the efficacy of treatment modality to a large extent. Although mRNA-LNP vaccine platforms for the COVID-19 pandemic demonstrated high efficiency, safety and adverse effects challenges due to the uncontrolled immune responses and inappropriate pharmacological interventions could limit this tremendous efficacy. The current study reveals the interplay of immune responses with LNP compositions and characterization and clarifies the interaction of mRNA-LNP therapeutics with dendritic, macrophages, neutrophile cells, and complement. Then, pharmacological profiles for mRNA-LNP delivery, including pharmacokinetics and cellular trafficking, were discussed in detail in cancer types and infectious diseases. This review study opens a new and vital landscape to improve multidisciplinary therapeutics on mRNA-LNP through modulation of immunopharmacological responses in clinical trials. Graphical Abstract

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Section: Pharmacological Study Of Mrna-lnp Deliverymentioning

confidence: 99%

Recent advances in mRNA-LNP therapeutics: immunological and pharmacological aspects

et al. 2022

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“…Eukaryotic mRNA consists of a 5′ cap, a 5′ untranslated region (UTR), an open reading frame (ORF), a 3′ UTR, and a poly(A) tail ( Cai et al, 2021 ). mRNA vaccine sequences also need to contain these elements.…”

Section: Sequence Construction and Delivery Optimization Of Mrna Vacc...mentioning

confidence: 99%

“…The mRNA in mRNA vaccines is transcribed in vitro ( Li et al, 2018 ). In vitro transcription (IVT) begins with an ORF encoding the target protein and a suitable UTR, followed by the addition of the 5′ cap and poly(A) tail ( Cai et al, 2021 ).…”

Section: Sequence Construction and Delivery Optimization Of Mrna Vacc...mentioning

confidence: 99%

mRNA vaccines: A novel weapon to control infectious diseases

2022

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Infectious diseases have always threatened human life, but with the development of vaccines, effective strategies for preventing and controlling these diseases have become available. The global outbreak of COVID-19 ushered in the advent of mRNA vaccine technologies, which quickly led to the introduction of mRNA vaccines effective against SARS-CoV-2. The success of this approach has stimulated research into the use of mRNA vaccines in the fight against other emerging as well as remerging infectious diseases. This review examines the constructive strategies and delivery systems used in mRNA vaccines and provides an overview of current clinical trials of those vaccines in the prevention of infectious diseases. The underlying mechanisms of mRNA vaccines are also discussed, including the double-edged sword of the innate immune response. Finally, the challenges but also the potential of mRNA vaccines are considered.

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“…The selected highly antigenic epitopes that are predicted for each target protein were then utilized in the design of an mRNA-based vaccine against A. xylosoxidans. Herein, 2 T-cell epitopes from each target protein were selected and a total of 6 CTL epitopes were included in the final whole proteome specific mRNA-based vaccine design (35). Similarly, a total of 6 HTL and 6 B-cell epitopes were included in the final mRNA vaccine candidate.…”

Section: Proteome-wide Mrna-based Vaccine Designmentioning

confidence: 99%

Evaluation of the Whole Proteome of Achromobacter xylosoxidans to Identify Vaccine Targets for mRNA and Peptides-Based Vaccine Designing Against the Emerging Respiratory and Lung Cancer-Causing Bacteria

Khan

Abdullah

Toor³

et al. 2022

Front. Med.

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Achromobacter xylosoxidans is a rod-shaped Gram-negative bacterium linked with causing several infections which mostly includes hematological malignancies. It has been recently reported to be associated with the development and progression of lung cancer and is an emerging respiratory disease-causing bacterium. The treatment of individuals infected with A. xylosoxidans bacteremia is difficult due to the fact that this pathogen has both intrinsic and acquired resistance mechanisms, typically resulting in a phenotype of multidrug resistance (MDR). Efforts are needed to design effective therapeutic strategies to curtail the emergence of this bacterium. Computational vaccine designing has proven its effectiveness, specificity, safety, and stability compared to conventional approaches of vaccine development. Therefore, the whole proteome of A. xylosoxidans was screened for the characterization of potential vaccine targets through subtractive proteomics pipeline for therapeutics design. Annotation of the whole proteome confirmed the three immunogenic vaccine targets, such as (E3HHR6), (E3HH04), and (E3HWA2), which were used to map the putative immune epitopes. The shortlisted epitopes, specific against Cytotoxic T Lymphocytes, Helper T-cell Lymphocytes, and linear B-Cell, were used to design the mRNA and multi-epitopes vaccine (MEVC). Initial validations confirmed the antigenic and non-allergenic properties of these constructs, followed by docking with the immune receptor, TLR-5, which resulted in robust interactions. The interaction pattern that followed in the docking complex included formation of 5 hydrogen bonds, 2 salt bridges, and 165 non-bonded contacts. This stronger binding affinity was also assessed through using the mmGBSA approach, showing a total of free binding energy of −34.64 kcal/mol. Further validations based on in silico cloning revealed a CAI score of 0.98 and an optimal percentage of GC contents (54.4%) indicated a putatively higher expression of the vaccine construct in Escherichia coli. Moreover, immune simulation revealed strong antibodies production upon the injection of the designed MEVC that resulted in the highest peaks of IgM+ IgG production (>3,500) between 10 and 15 days. In conclusion the current study provide basis for vaccine designing against the emerging A. xylosoxidans, which demands further experimental studies for in vitro and in vivo validations.

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Infectious disease mRNA vaccines and a review on epitope prediction for vaccine design

Cited by 21 publications

References 83 publications

Recent advances in mRNA-LNP therapeutics: immunological and pharmacological aspects

Recent advances in mRNA-LNP therapeutics: immunological and pharmacological aspects

mRNA vaccines: A novel weapon to control infectious diseases

Evaluation of the Whole Proteome of Achromobacter xylosoxidans to Identify Vaccine Targets for mRNA and Peptides-Based Vaccine Designing Against the Emerging Respiratory and Lung Cancer-Causing Bacteria

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