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Generation of a Live-Attenuated Strain of Chikungunya Virus from an Indian Isolate for Vaccine Development
Chikungunya virus (CHIKV) re-emergence in the last decade has resulted in explosive epidemics. Along with the classical symptoms of fever and debilitating arthralgia, there were occurrences of unusual clinical presentations such as neurovirulence and mortality. These generated a renewed global inter...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697353/ https://www.ncbi.nlm.nih.gov/pubmed/36423034 http://dx.doi.org/10.3390/vaccines10111939 |
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author | Nair, Sreeja R. Abraham, Rachy Sreekumar, Easwaran |
author_facet | Nair, Sreeja R. Abraham, Rachy Sreekumar, Easwaran |
author_sort | Nair, Sreeja R. |
collection | PubMed |
description | Chikungunya virus (CHIKV) re-emergence in the last decade has resulted in explosive epidemics. Along with the classical symptoms of fever and debilitating arthralgia, there were occurrences of unusual clinical presentations such as neurovirulence and mortality. These generated a renewed global interest to develop prophylactic vaccines. Here, using the classical approach of virus attenuation, we developed an attenuated CHIKV strain (RGCB355/KL08-p75) for the purpose. Repeated passaging (75 times) of a local clinical isolate of ECSA lineage virus in U-87 MG human astrocytoma cells, an interferon-response-deficient cell line, resulted in efficient adaptation and attenuation. While experimental infection of 3-day old CHIKV-susceptible BALB/c pups with the parent strain RGCB355/KL08-p4 resulted in death of all the animals, there was 100% survival in mice infected with the attenuated p75. In adult, immunocompetent, CHIKV-non-susceptible C57BL/6 mice, inoculation with p75 induced high antibody response without any signs of disease. Both p4 and p75 strains are uniformly lethal to interferon-response-deficient AG129 mice. Passive protection studies in AG129 mice using immune serum against p75 resulted in complete survival. Whole-genome sequencing identified novel mutations that might be responsible for virus attenuation. Our results establish the usefulness of RGCB355/KL08-p75 as a strain for vaccine development against chikungunya. |
format | Online Article Text |
id | pubmed-9697353 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96973532022-11-26 Generation of a Live-Attenuated Strain of Chikungunya Virus from an Indian Isolate for Vaccine Development Nair, Sreeja R. Abraham, Rachy Sreekumar, Easwaran Vaccines (Basel) Article Chikungunya virus (CHIKV) re-emergence in the last decade has resulted in explosive epidemics. Along with the classical symptoms of fever and debilitating arthralgia, there were occurrences of unusual clinical presentations such as neurovirulence and mortality. These generated a renewed global interest to develop prophylactic vaccines. Here, using the classical approach of virus attenuation, we developed an attenuated CHIKV strain (RGCB355/KL08-p75) for the purpose. Repeated passaging (75 times) of a local clinical isolate of ECSA lineage virus in U-87 MG human astrocytoma cells, an interferon-response-deficient cell line, resulted in efficient adaptation and attenuation. While experimental infection of 3-day old CHIKV-susceptible BALB/c pups with the parent strain RGCB355/KL08-p4 resulted in death of all the animals, there was 100% survival in mice infected with the attenuated p75. In adult, immunocompetent, CHIKV-non-susceptible C57BL/6 mice, inoculation with p75 induced high antibody response without any signs of disease. Both p4 and p75 strains are uniformly lethal to interferon-response-deficient AG129 mice. Passive protection studies in AG129 mice using immune serum against p75 resulted in complete survival. Whole-genome sequencing identified novel mutations that might be responsible for virus attenuation. Our results establish the usefulness of RGCB355/KL08-p75 as a strain for vaccine development against chikungunya. MDPI 2022-11-16 /pmc/articles/PMC9697353/ /pubmed/36423034 http://dx.doi.org/10.3390/vaccines10111939 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nair, Sreeja R. Abraham, Rachy Sreekumar, Easwaran Generation of a Live-Attenuated Strain of Chikungunya Virus from an Indian Isolate for Vaccine Development |
title | Generation of a Live-Attenuated Strain of Chikungunya Virus from an Indian Isolate for Vaccine Development |
title_full | Generation of a Live-Attenuated Strain of Chikungunya Virus from an Indian Isolate for Vaccine Development |
title_fullStr | Generation of a Live-Attenuated Strain of Chikungunya Virus from an Indian Isolate for Vaccine Development |
title_full_unstemmed | Generation of a Live-Attenuated Strain of Chikungunya Virus from an Indian Isolate for Vaccine Development |
title_short | Generation of a Live-Attenuated Strain of Chikungunya Virus from an Indian Isolate for Vaccine Development |
title_sort | generation of a live-attenuated strain of chikungunya virus from an indian isolate for vaccine development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697353/ https://www.ncbi.nlm.nih.gov/pubmed/36423034 http://dx.doi.org/10.3390/vaccines10111939 |
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