Identifying immunodominant multi-epitopes from the envelope glycoprotein of the Lassa mammarenavirus as vaccine candidate for Lassa fever

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Abstract

Purpose

Lassa fever is a zoonotic acute viral hemorrhagic disease caused by Lassa virus (LASV). There is currently no licensed vaccine for the prevention of the disease. This study is aimed at discovering immunodominant epitopes from the envelope glycoprotein of the Lassa mammarenavirus and designing of a multi-epitope vaccine candidate (VC).

Materials and Methods

The amino acid sequences of the envelope glycoprotein of 26 strains of LASV from five countries were selected. After evaluation for antigenicity, immunogenicity, allergenicity, and toxicity, immunodominant CD8, CD4, and linear B lymphocytes were also selected. The selected epitopes were modelled and a molecular docking with the appropriate major histocompatibility complex (MHC) proteins was performed. Using an adjuvant and linkers, a multi-epitope VC was designed. The VC was evaluated for its physicochemical and immunological properties and structurally refined, validated, and mutated (disulphide engineering). The complex formed by the VC and the toll-like receptor-4 receptor was subjected to molecular dynamic simulation (MDS) followed by in silico cloning in a plasmid vector.

Results

A VC with 203 sequences, 22.13 kDa weight, isoelectric point of 9.85 (basic), instability index value of 27.62, aliphatic index of 68.87, and GRAVY value of -0.455 (hydrophilic) emerged. The VC is predicted to be non-allergenic with antigenicity, MHC I immunogenicity, and solubility upon overexpression values of 0.81, 2.04, and 0.86 respectively. The VC also has an estimated half-life greater than 10 hours in Escherichia coli and showed stability in all the parameters of MDS.

Conclusion

The VC shows good promise in the prevention of Lassa fever but further tests are required to validate its safety and efficacy.

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MolProbity: More and better reference data for improved all-atom structure validation.

Christopher J Williams, Jeffrey J. Headd, Nigel Moriarty … (2018)

This paper describes the current update on macromolecular model validation services that are provided at the MolProbity website, emphasizing changes and additions since the previous review in 2010. There have been many infrastructure improvements, including rewrite of previous Java utilities to now use existing or newly written Python utilities in the open-source CCTBX portion of the Phenix software system. This improves long-term maintainability and enhances the thorough integration of MolProbity-style validation within Phenix. There is now a complete MolProbity mirror site at http://molprobity.manchester.ac.uk. GitHub serves our open-source code, reference datasets, and the resulting multi-dimensional distributions that define most validation criteria. Coordinate output after Asn/Gln/His "flip" correction is now more idealized, since the post-refinement step has apparently often been skipped in the past. Two distinct sets of heavy-atom-to-hydrogen distances and accompanying van der Waals radii have been researched and improved in accuracy, one for the electron-cloud-center positions suitable for X-ray crystallography and one for nuclear positions. New validations include messages at input about problem-causing format irregularities, updates of Ramachandran and rotamer criteria from the million quality-filtered residues in a new reference dataset, the CaBLAM Cα-CO virtual-angle analysis of backbone and secondary structure for cryoEM or low-resolution X-ray, and flagging of the very rare cis-nonProline and twisted peptides which have recently been greatly overused. Due to wide application of MolProbity validation and corrections by the research community, in Phenix, and at the worldwide Protein Data Bank, newly deposited structures have continued to improve greatly as measured by MolProbity's unique all-atom clashscore.

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Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants

Yiska Weisblum, Fabian Schmidt, Fengwen Zhang … (2020)

Neutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional SARS-CoV-2 S protein variants with mutations in the receptor-binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected. Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations. Finally, the emergence of antibody-resistant SARS-CoV-2 variants that might limit the therapeutic usefulness of monoclonal antibodies can be mitigated by the use of antibody combinations that target distinct neutralizing epitopes.

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Author and article information

Journal

Journal ID (nlm-ta): Clin Exp Vaccine Res

Journal ID (iso-abbrev): Clin Exp Vaccine Res

Journal ID (publisher-id): CEVR

Title: Clinical and Experimental Vaccine Research

Publisher: The Korean Vaccine Society

ISSN (Print): 2287-3651

ISSN (Electronic): 2287-366X

Publication date (Print): September 2022

Publication date (Electronic): 30 September 2022

Volume: 11

Issue: 3

Pages: 249-263

Affiliations

[1 ]National Biotechnology Development Agency, Abuja, Nigeria.

[2 ]Department of Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka, Nigeria.

[3 ]Department of Anatomy, Baze University, Abuja, Nigeria.

Author notes

Corresponding author: Angus Nnamdi Oli, PhD. Department of Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka, Nigeria. Tel: +234-8056306927, Fax: +234-8056306927, an.oli@ 123456unizik.edu.ng

Author information

Adekunle Babajide Rowaiye https://orcid.org/0000-0002-8773-5944

Ezinne Janefrances Nwonu https://orcid.org/0000-0001-8392-9170

Titilayo Mercy Asala https://orcid.org/0000-0003-3464-2936

Amoge Chidinma Ogu https://orcid.org/0000-0003-3461-2737

Doofan Bur https://orcid.org/0000-0001-7625-7118

Chimaobi Chukwu https://orcid.org/0000-0003-2411-0290

Angus Nnamdi Oli https://orcid.org/0000-0001-8519-2555

Tarimoboere Agbalalah https://orcid.org/0000-0002-5875-4126

Article

DOI: 10.7774/cevr.2022.11.3.249

PMC ID: 9691867

PubMed ID: 36451670

SO-VID: 1b4381b6-9c47-4ca6-a10b-69f1f194ab5d

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 26 May 2022

Date accepted : 26 July 2022

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Lassa fever vaccine prospects: identifying immunodominant multi-epitopes as vaccine candidate
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Identifying immunodominant multi-epitopes from the envelope glycoprotein of the Lassa mammarenavirus as vaccine candidate for Lassa fever

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Abstract

Purpose

Materials and Methods

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Malaria vaccine development

Most cited references 40

MolProbity: More and better reference data for improved all-atom structure validation.

The codon Adaptation Index--a measure of directional synonymous codon usage bias, and its potential applications.

Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants

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