Cargando…

In silico Design of a Multivalent Vaccine Against Candida albicans

Invasive candidiasis (IC) is the most common nosocomial infection and a leading cause of mycoses-related deaths. High-systemic toxicity and emergence of antifungal-resistant species warrant the development of newer preventive approaches against IC. Here, we have adopted an immunotherapeutic peptide...

Descripción completa

Detalles Bibliográficos
Autores principales: Tarang, Shikha, Kesherwani, Varun, LaTendresse, Blake, Lindgren, Laramie, Rocha-Sanchez, Sonia M., Weston, Michael D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978452/
https://www.ncbi.nlm.nih.gov/pubmed/31974431
http://dx.doi.org/10.1038/s41598-020-57906-x
_version_ 1783490703914958848
author Tarang, Shikha
Kesherwani, Varun
LaTendresse, Blake
Lindgren, Laramie
Rocha-Sanchez, Sonia M.
Weston, Michael D.
author_facet Tarang, Shikha
Kesherwani, Varun
LaTendresse, Blake
Lindgren, Laramie
Rocha-Sanchez, Sonia M.
Weston, Michael D.
author_sort Tarang, Shikha
collection PubMed
description Invasive candidiasis (IC) is the most common nosocomial infection and a leading cause of mycoses-related deaths. High-systemic toxicity and emergence of antifungal-resistant species warrant the development of newer preventive approaches against IC. Here, we have adopted an immunotherapeutic peptide vaccine-based approach, to enhance the body’s immune response against invasive candida infections. Using computational tools, we screened the entire candida proteome (6030 proteins) and identified the most immunodominant HLA class I, HLA class II and B- cell epitopes. By further immunoinformatic analyses for enhanced vaccine efficacy, we selected the 18- most promising epitopes, which were joined together using molecular linkers to create a multivalent recombinant protein against Candida albicans (mvPC). To increase mvPC’s immunogenicity, we added a synthetic adjuvant (RS09) to the mvPC design. The selected mvPC epitopes are homologous against all currently available annotated reference sequences of 22 C. albicans strains, thus offering a higher coverage and greater protective response. A major advantage of the current vaccine approach is mvPC’s multivalent nature (recognizing multiple-epitopes), which is likely to provide enhanced protection against complex candida antigens. Here, we describe the computational analyses leading to mvPC design.
format Online
Article
Text
id pubmed-6978452
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-69784522020-01-30 In silico Design of a Multivalent Vaccine Against Candida albicans Tarang, Shikha Kesherwani, Varun LaTendresse, Blake Lindgren, Laramie Rocha-Sanchez, Sonia M. Weston, Michael D. Sci Rep Article Invasive candidiasis (IC) is the most common nosocomial infection and a leading cause of mycoses-related deaths. High-systemic toxicity and emergence of antifungal-resistant species warrant the development of newer preventive approaches against IC. Here, we have adopted an immunotherapeutic peptide vaccine-based approach, to enhance the body’s immune response against invasive candida infections. Using computational tools, we screened the entire candida proteome (6030 proteins) and identified the most immunodominant HLA class I, HLA class II and B- cell epitopes. By further immunoinformatic analyses for enhanced vaccine efficacy, we selected the 18- most promising epitopes, which were joined together using molecular linkers to create a multivalent recombinant protein against Candida albicans (mvPC). To increase mvPC’s immunogenicity, we added a synthetic adjuvant (RS09) to the mvPC design. The selected mvPC epitopes are homologous against all currently available annotated reference sequences of 22 C. albicans strains, thus offering a higher coverage and greater protective response. A major advantage of the current vaccine approach is mvPC’s multivalent nature (recognizing multiple-epitopes), which is likely to provide enhanced protection against complex candida antigens. Here, we describe the computational analyses leading to mvPC design. Nature Publishing Group UK 2020-01-23 /pmc/articles/PMC6978452/ /pubmed/31974431 http://dx.doi.org/10.1038/s41598-020-57906-x Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Tarang, Shikha
Kesherwani, Varun
LaTendresse, Blake
Lindgren, Laramie
Rocha-Sanchez, Sonia M.
Weston, Michael D.
In silico Design of a Multivalent Vaccine Against Candida albicans
title In silico Design of a Multivalent Vaccine Against Candida albicans
title_full In silico Design of a Multivalent Vaccine Against Candida albicans
title_fullStr In silico Design of a Multivalent Vaccine Against Candida albicans
title_full_unstemmed In silico Design of a Multivalent Vaccine Against Candida albicans
title_short In silico Design of a Multivalent Vaccine Against Candida albicans
title_sort in silico design of a multivalent vaccine against candida albicans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978452/
https://www.ncbi.nlm.nih.gov/pubmed/31974431
http://dx.doi.org/10.1038/s41598-020-57906-x
work_keys_str_mv AT tarangshikha insilicodesignofamultivalentvaccineagainstcandidaalbicans
AT kesherwanivarun insilicodesignofamultivalentvaccineagainstcandidaalbicans
AT latendresseblake insilicodesignofamultivalentvaccineagainstcandidaalbicans
AT lindgrenlaramie insilicodesignofamultivalentvaccineagainstcandidaalbicans
AT rochasanchezsoniam insilicodesignofamultivalentvaccineagainstcandidaalbicans
AT westonmichaeld insilicodesignofamultivalentvaccineagainstcandidaalbicans