An immunoinformatics and extensive molecular dynamics study to develop a polyvalent multi-epitope vaccine against cryptococcosis.
Cryptococcosis is a lethal mycosis instigated by the pathogenic species Cryptococcus neoformans and Cryptococcus gattii, primarily affects the lungs, manifesting as pneumonia, and the brain, where it presents as meningitis. Mortality rate could reach 100% if infections remain untreated in cryptococc...
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| Format: | Article |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0315105 |
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| author | Md Razwan Sardar Sami Nurul Amin Rani Mohammad Mahfuz Enam Elahi Mohammad Sajjad Hossain Minhaz Abdullah Al Mueid Zahidur Rahim Rajesh B Patil Abu Tayab Moin Israt Jahan Bithi Sabekun Nahar Israt Jahan Konika Sneha Roy Jannatul Aleya Preya Jamil Ahmed |
| author_facet | Md Razwan Sardar Sami Nurul Amin Rani Mohammad Mahfuz Enam Elahi Mohammad Sajjad Hossain Minhaz Abdullah Al Mueid Zahidur Rahim Rajesh B Patil Abu Tayab Moin Israt Jahan Bithi Sabekun Nahar Israt Jahan Konika Sneha Roy Jannatul Aleya Preya Jamil Ahmed |
| author_sort | Md Razwan Sardar Sami |
| collection | DOAJ |
| description | Cryptococcosis is a lethal mycosis instigated by the pathogenic species Cryptococcus neoformans and Cryptococcus gattii, primarily affects the lungs, manifesting as pneumonia, and the brain, where it presents as meningitis. Mortality rate could reach 100% if infections remain untreated in cryptococcal meningitis. Treatment options for cryptococcosis are limited and and there are no licensed vaccines clinically available to treat or prevent cryptococcosis. Our study utilizes an integrated bioinformatics approaches to develop a polyvalent multiepitope subunit vaccine focusing on the key virulent proteins Heat shock transcription factor and Chaperone DnaK of both C. neoformans and C. gatti. Then in silico analysis was done to predict highly antigenic epitopes by assessing antigenicity, transmembrane topology screening, allergenecity, toxicity, and molecular docking approaches. Following this analysis, we designed two vaccine constructs integrating a compatible adjuvant and suitable linkers. These constructs exhibited notable characteristics including high antigenicity, non-toxicity, solubility, stability, and compatibility with Toll-like receptors (TLRs). The interaction between both vaccine constructs and TLR2, TLR3, and TLR9 was assessed through molecular docking analysis. Molecular dynamics simulations and MM-PBSA calculations suggest the substantial stabilizing property and binding affinity of Vaccine Construct V1 against TLR9. Both the vaccines revealed to have a higher number of interchain hydrogen bond with TLR9. These findings serve as a crucial stepping stone towards a comprehensive solution for combating cryptococcus infections induced by both C. neoformans and C. gattii. Further validation through in vivo studies is crucial to confirm the effectiveness and potential of the vaccine to curb the spread of cryptococcosis. Subsequent validation through in vivo studies is paramount to confirm the effectiveness and potential of the vaccine in reducing the spread of cryptococcosis. |
| format | Article |
| id | doaj-art-30b41ecf7ba24c2ea431232e7e65eb52 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-30b41ecf7ba24c2ea431232e7e65eb522025-08-20T02:26:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011912e031510510.1371/journal.pone.0315105An immunoinformatics and extensive molecular dynamics study to develop a polyvalent multi-epitope vaccine against cryptococcosis.Md Razwan Sardar SamiNurul Amin RaniMohammad Mahfuz Enam ElahiMohammad Sajjad HossainMinhaz Abdullah Al MueidZahidur RahimRajesh B PatilAbu Tayab MoinIsrat Jahan BithiSabekun NaharIsrat Jahan KonikaSneha RoyJannatul Aleya PreyaJamil AhmedCryptococcosis is a lethal mycosis instigated by the pathogenic species Cryptococcus neoformans and Cryptococcus gattii, primarily affects the lungs, manifesting as pneumonia, and the brain, where it presents as meningitis. Mortality rate could reach 100% if infections remain untreated in cryptococcal meningitis. Treatment options for cryptococcosis are limited and and there are no licensed vaccines clinically available to treat or prevent cryptococcosis. Our study utilizes an integrated bioinformatics approaches to develop a polyvalent multiepitope subunit vaccine focusing on the key virulent proteins Heat shock transcription factor and Chaperone DnaK of both C. neoformans and C. gatti. Then in silico analysis was done to predict highly antigenic epitopes by assessing antigenicity, transmembrane topology screening, allergenecity, toxicity, and molecular docking approaches. Following this analysis, we designed two vaccine constructs integrating a compatible adjuvant and suitable linkers. These constructs exhibited notable characteristics including high antigenicity, non-toxicity, solubility, stability, and compatibility with Toll-like receptors (TLRs). The interaction between both vaccine constructs and TLR2, TLR3, and TLR9 was assessed through molecular docking analysis. Molecular dynamics simulations and MM-PBSA calculations suggest the substantial stabilizing property and binding affinity of Vaccine Construct V1 against TLR9. Both the vaccines revealed to have a higher number of interchain hydrogen bond with TLR9. These findings serve as a crucial stepping stone towards a comprehensive solution for combating cryptococcus infections induced by both C. neoformans and C. gattii. Further validation through in vivo studies is crucial to confirm the effectiveness and potential of the vaccine to curb the spread of cryptococcosis. Subsequent validation through in vivo studies is paramount to confirm the effectiveness and potential of the vaccine in reducing the spread of cryptococcosis.https://doi.org/10.1371/journal.pone.0315105 |
| spellingShingle | Md Razwan Sardar Sami Nurul Amin Rani Mohammad Mahfuz Enam Elahi Mohammad Sajjad Hossain Minhaz Abdullah Al Mueid Zahidur Rahim Rajesh B Patil Abu Tayab Moin Israt Jahan Bithi Sabekun Nahar Israt Jahan Konika Sneha Roy Jannatul Aleya Preya Jamil Ahmed An immunoinformatics and extensive molecular dynamics study to develop a polyvalent multi-epitope vaccine against cryptococcosis. PLoS ONE |
| title | An immunoinformatics and extensive molecular dynamics study to develop a polyvalent multi-epitope vaccine against cryptococcosis. |
| title_full | An immunoinformatics and extensive molecular dynamics study to develop a polyvalent multi-epitope vaccine against cryptococcosis. |
| title_fullStr | An immunoinformatics and extensive molecular dynamics study to develop a polyvalent multi-epitope vaccine against cryptococcosis. |
| title_full_unstemmed | An immunoinformatics and extensive molecular dynamics study to develop a polyvalent multi-epitope vaccine against cryptococcosis. |
| title_short | An immunoinformatics and extensive molecular dynamics study to develop a polyvalent multi-epitope vaccine against cryptococcosis. |
| title_sort | immunoinformatics and extensive molecular dynamics study to develop a polyvalent multi epitope vaccine against cryptococcosis |
| url | https://doi.org/10.1371/journal.pone.0315105 |
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