Design of peptide-based epitope vaccine and further binding site scrutiny led to groundswell in drug discovery against Lassa virus

Hossain, Mohammad Uzzal; Omar, Taimur Md; Oany, Arafat Rahman; Kibria, K. M. Kaderi; Shibly, Abu Zaffar; Moniruzzaman, Mohammad; Ali, Syed Raju; Islam, Md. Monirul

doi:10.1007/s13205-018-1106-5

Cited by 16 publications

(13 citation statements)

References 63 publications

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“…The LASV GP spike has emerged as a promising selective target for the development of novel vaccines as it plays an essential role in the virus-host interaction. Several in-silico studies [62][63][64][65][66][67] were performed to predict LASV GP epitopes with the use of a single prediction tool for each type of epitope. We have identified new T and B-cell epitopes using a variety of computational approaches, including twelve epitope prediction methods, protein-peptide docking, and MD simulations.…”

Section: Resultsmentioning

confidence: 99%

“…For these epitopes, a comparison showing the overlap between the predicted epitopes in this study and previously known epitopes documented in IEDB is given in Table S5. In addition to the epitopes in the IEDB, we compared our consensus predicted epitopes with the previously reported predictions [62][63][64][65][66][67] in Table S6. This comparison shows a varying degree of overlap in the predicted sequences.…”

Section: Dynamics Of the Allele-epitope Complexmentioning

confidence: 99%

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In-silico identification of the vaccine candidate epitopes against the Lassa virus hemorrhagic fever

Baral

Pavadai

Gerstman

et al. 2020

Sci Rep

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Lassa virus (LASV), a member of the Arenaviridae, is an ambisense RNA virus that causes severe hemorrhagic fever with a high fatality rate in humans in West and Central Africa. Currently, no FDA approved drugs or vaccines are available for the treatment of LASV fever. The LASV glycoprotein complex (GP) is a promising target for vaccine or drug development. It is situated on the virion envelope and plays key roles in LASV growth, cell tropism, host range, and pathogenicity. In an effort to discover new LASV vaccines, we employ several sequence-based computational prediction tools to identify LASV GP major histocompatibility complex (MHC) class I and II T-cell epitopes. In addition, many sequence-and structure-based computational prediction tools were used to identify LASV GP B-cell epitopes. The predicted T-and B-cell epitopes were further filtered based on the consensus approach that resulted in the identification of thirty new epitopes that have not been previously tested experimentally. Epitope-allele complexes were obtained for selected strongly binding alleles to the MHC-I T-cell epitopes using molecular docking and the complexes were relaxed with molecular dynamics simulations to investigate the interaction and dynamics of the epitope-allele complexes. These predictions provide guidance to the experimental investigations and validation of the epitopes with the potential for stimulating T-cell responses and B-cell antibodies against LASV and allow the design and development of LASV vaccines.Lassa virus (LASV), a member of the Arenaviridae 1 , is an ambisense RNA virus that causes a severe hemorrhagic Lassa fever in humans. LASV is endemic, particularly in the West African countries of Sierra Leone, The Republic of Guinea, Nigeria, and Liberia 2,3 . The transmission of LASV to humans occurs through the urine or feces of infected Mastomys rats and the virus spreads human-to-human through direct contact with the blood, urine, feces, or other bodily secretions of an infected person. LASV can be fatal and no approved effective therapeutics are currently available. The development of therapeutics such as antibodies and vaccines for the treatment of LASV is therefore of significant urgency 4-6 .Of the four proteins that are encoded by the two RNA segments of the LASV genome, the glycoprotein (GP) is the only protein on the viral surface. GP results from the cleavage of a 75 kDa precursor polypeptide, GPC by signal peptidase and then further glycosylated and processed into GP1 and GP2 7 . GP1 is the receptor-binding subunit, and GP2 is the membrane-spanning fusion subunit 8-10 . The virion envelope protein spikes are composed of three heterotrimers, with each heterotrimer containing signal peptide, GP1, and GP2 11,12 , shown in Fig. 1. A chalice-like GP trimer interacts with receptors on the cell surface, for example matriglycan, which mediates the entry of the virus into the host cell. In addition, the GP also interact with ERGIC-53 in the exocytic pathway, which helps to form infectious virions 13 . GP is considere...

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Section: Resultsmentioning

confidence: 99%

Section: Dynamics Of the Allele-epitope Complexmentioning

confidence: 99%

In-silico identification of the vaccine candidate epitopes against the Lassa virus hemorrhagic fever

Baral

Pavadai

Gerstman

et al. 2020

Sci Rep

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“…143,144 In another example, sequence analysis of Lassa fever virus (the LASV) and other viruses' immunoproteomic was used to identify the best immunogenic protein predicting T-cell as well as B-cell epitopes and also target sequence and binding sites. 145,146 The SSNLYKGVY peptide sequence at AA41-49 of glycoprotein 1 (produced by the L segment) was the best candidate epitope for the induction of humoral as well as the cell-mediated immunity for Lassa fever vaccine construct. 17 HLA-I and 16 HLA-II molecules have been proven in sizable African populations and their combination with the SSNLYKGVY peptide sequence may prove useful in such Lassa fever virus endemic areas.…”

Section: The Subpopulation Levelmentioning

confidence: 99%

“…17 HLA-I and 16 HLA-II molecules have been proven in sizable African populations and their combination with the SSNLYKGVY peptide sequence may prove useful in such Lassa fever virus endemic areas. 145 This approach will strongly improve individualized vaccination and help combat emerging infections. The HLA region is suspected to contribute, to a large extent, to genetic propensity to infections and differences in vaccine expected immune responses.…”

Section: The Subpopulation Levelmentioning

confidence: 99%

<p>Immunoinformatics and Vaccine Development: An Overview</p>

Oli

Obialor

Ifeanyichukwu

et al. 2020

ITT

177

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The use of vaccines have resulted in a remarkable improvement in global health. It has saved several lives, reduced treatment costs and raised the quality of animal and human lives. Current traditional vaccines came empirically with either vague or completely no knowledge of how they modulate our immune system. Even at the face of potential vaccine design advance, immune-related concerns (as seen with specific vulnerable populations, cases of emerging/reemerging infectious disease, pathogens with complex lifecycle and antigenic variability, need for personalized vaccinations, and concerns for vaccines' immunological safety -specifically vaccine likelihood to trigger non-antigen-specific responses that may cause autoimmunity and vaccine allergy) are being raised. And these concerns have driven immunologists toward research for a better approach to vaccine design that will consider these challenges. Currently, immunoinformatics has paved the way for a better understanding of some infectious disease pathogenesis, diagnosis, immune system response and computational vaccinology. The importance of this immunoinformatics in the study of infectious diseases is diverse in terms of computational approaches used, but is united by common qualities related to host-pathogen relationship. Bioinformatics methods are also used to assign functions to uncharacterized genes which can be targeted as a candidate in vaccine design and can be a better approach toward the inclusion of women that are pregnant into vaccine trials and programs. The essence of this review is to give insight into the need to focus on novel computational, experimental and computation-driven experimental approaches for studying of host-pathogen interactions and thus making a case for its use in vaccine development.

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“…at AA41-49 of glycoprotein (GP1) encoded by the L segment was found to represent the most potential epitope. This peptide sequence might intermingle with 17 HLA-I and 16 HLA-II molecules, covering 49.15-96.82% of the population of common people in different African countries, where the Lassa virus is endemic [96].…”

Section: Some Examples Of Experimental Peptide Vaccines Based On Selementioning

confidence: 99%

Peptide Vaccines: New Trends for Avoiding the Autoimmune Response

Rajčáni¹,

Szathmáry²

2018

TOIDJ

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Background:Several marketed antiviral vaccines (such as that against hepatitis virus A and/or B, influenza virus, human papillomavirus, yellow fever virus, measles, rubella and mumps viruses) may elicit various autoimmune reactions.Results:The cause of autoimmune response due to vaccination may be: 1. the adjuvant which is regularly added to the vaccine (especially in the case of various oil substrates), 2. the specific viral component itself (a protein or glycoprotein potentially possessing cross-reactive epitopes) and/or 3. contamination of the vaccine with traces of non-viral proteins mostly cellular in origin. Believing that peptide vaccines might represent an optimal solution for avoiding the above-mentioned problems, we discuss the principles of rational design of a typical peptide vaccine which should contain oligopeptides coming either from the selected structural virion components (i.e.capsid proteins and/or envelop glycoproteins or both) or from the virus-coded non-structural polypeptides. The latter should be equally immunogenic as the structural virus proteins. Describing the feasibility of identification and design of immunogenic epitopes, our paper also deals with possible problems of peptide vaccine manufacturing. The presented data are in part based on the experience of our own, in part, they are coming from the results published by others.Conclusion:Any peptide vaccine should be able to elicit relevant and specific antibody formation, as well as an efficient cell-mediated immune response. Consequently, the properly designed peptide vaccine is expected to consist of carefully selected viral peptides, which should stimulate the receptors of helper T/CD4 cells as well as of cytotoxic (T/CD8) lymphocytes.

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Design of peptide-based epitope vaccine and further binding site scrutiny led to groundswell in drug discovery against Lassa virus

Cited by 16 publications

References 63 publications

In-silico identification of the vaccine candidate epitopes against the Lassa virus hemorrhagic fever

In-silico identification of the vaccine candidate epitopes against the Lassa virus hemorrhagic fever

<p>Immunoinformatics and Vaccine Development: An Overview</p>

Peptide Vaccines: New Trends for Avoiding the Autoimmune Response

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