Live-attenuated CHIKV vaccine with rearranged genome replicates in vitro and induces immune response in mice.
Chikungunya fever virus (CHIKV) is a mosquito-borne alphavirus that causes wide-spread human infections and epidemics in Asia, Africa and recently, in the Americas. CHIKV is considered a priority pathogen by CEPI and WHO. Despite recent approval of a live-attenuated CHIKV vaccine, development of add...
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ftdoajarticles:oai:doaj.org/article:9b58470d827541d1a7b6317f99368d22 2024-09-09T19:26:30+00:00 Live-attenuated CHIKV vaccine with rearranged genome replicates in vitro and induces immune response in mice. Irina Tretyakova Joongho Joh Mary Gearon Jennifer Kraenzle Sidney Goedeker Ava Pignataro Brian Alejandro Igor S Lukashevich Donghoon Chung Peter Pushko 2024-04-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0012120 https://doaj.org/article/9b58470d827541d1a7b6317f99368d22 EN eng Public Library of Science (PLoS) https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0012120&type=printable https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0012120 https://doaj.org/article/9b58470d827541d1a7b6317f99368d22 PLoS Neglected Tropical Diseases, Vol 18, Iss 4, p e0012120 (2024) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2024 ftdoajarticles https://doi.org/10.1371/journal.pntd.0012120 2024-08-05T17:49:23Z Chikungunya fever virus (CHIKV) is a mosquito-borne alphavirus that causes wide-spread human infections and epidemics in Asia, Africa and recently, in the Americas. CHIKV is considered a priority pathogen by CEPI and WHO. Despite recent approval of a live-attenuated CHIKV vaccine, development of additional vaccines is warranted due to the worldwide outbreaks of CHIKV. Previously, we developed immunization DNA (iDNA) plasmid capable of launching live-attenuated CHIKV vaccine in vivo. Here we report the use of CHIKV iDNA plasmid to prepare a novel, live-attenuated CHIKV vaccine V5040 with rearranged RNA genome. In V5040, genomic RNA was rearranged to encode capsid gene downstream from the glycoprotein genes. Attenuated mutations derived from experimental CHIKV 181/25 vaccine were also engineered into E2 gene of V5040. The DNA copy of rearranged CHIKV genomic RNA with attenuated mutations was cloned into iDNA plasmid pMG5040 downstream from the CMV promoter. After transfection in vitro, pMG5040 launched replication of V5040 virus with rearranged genome and attenuating E2 mutations. Furthermore, V5040 virus was evaluated in experimental murine models for general safety and immunogenicity. Vaccination with V5040 virus subcutaneously resulted in elicitation of CHIKV-specific, virus-neutralizing antibodies. The results warrant further evaluation of V5040 virus with rearranged genome as a novel live-attenuated vaccine for CHIKV. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 18 4 e0012120 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Irina Tretyakova Joongho Joh Mary Gearon Jennifer Kraenzle Sidney Goedeker Ava Pignataro Brian Alejandro Igor S Lukashevich Donghoon Chung Peter Pushko Live-attenuated CHIKV vaccine with rearranged genome replicates in vitro and induces immune response in mice. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Chikungunya fever virus (CHIKV) is a mosquito-borne alphavirus that causes wide-spread human infections and epidemics in Asia, Africa and recently, in the Americas. CHIKV is considered a priority pathogen by CEPI and WHO. Despite recent approval of a live-attenuated CHIKV vaccine, development of additional vaccines is warranted due to the worldwide outbreaks of CHIKV. Previously, we developed immunization DNA (iDNA) plasmid capable of launching live-attenuated CHIKV vaccine in vivo. Here we report the use of CHIKV iDNA plasmid to prepare a novel, live-attenuated CHIKV vaccine V5040 with rearranged RNA genome. In V5040, genomic RNA was rearranged to encode capsid gene downstream from the glycoprotein genes. Attenuated mutations derived from experimental CHIKV 181/25 vaccine were also engineered into E2 gene of V5040. The DNA copy of rearranged CHIKV genomic RNA with attenuated mutations was cloned into iDNA plasmid pMG5040 downstream from the CMV promoter. After transfection in vitro, pMG5040 launched replication of V5040 virus with rearranged genome and attenuating E2 mutations. Furthermore, V5040 virus was evaluated in experimental murine models for general safety and immunogenicity. Vaccination with V5040 virus subcutaneously resulted in elicitation of CHIKV-specific, virus-neutralizing antibodies. The results warrant further evaluation of V5040 virus with rearranged genome as a novel live-attenuated vaccine for CHIKV. |
format |
Article in Journal/Newspaper |
author |
Irina Tretyakova Joongho Joh Mary Gearon Jennifer Kraenzle Sidney Goedeker Ava Pignataro Brian Alejandro Igor S Lukashevich Donghoon Chung Peter Pushko |
author_facet |
Irina Tretyakova Joongho Joh Mary Gearon Jennifer Kraenzle Sidney Goedeker Ava Pignataro Brian Alejandro Igor S Lukashevich Donghoon Chung Peter Pushko |
author_sort |
Irina Tretyakova |
title |
Live-attenuated CHIKV vaccine with rearranged genome replicates in vitro and induces immune response in mice. |
title_short |
Live-attenuated CHIKV vaccine with rearranged genome replicates in vitro and induces immune response in mice. |
title_full |
Live-attenuated CHIKV vaccine with rearranged genome replicates in vitro and induces immune response in mice. |
title_fullStr |
Live-attenuated CHIKV vaccine with rearranged genome replicates in vitro and induces immune response in mice. |
title_full_unstemmed |
Live-attenuated CHIKV vaccine with rearranged genome replicates in vitro and induces immune response in mice. |
title_sort |
live-attenuated chikv vaccine with rearranged genome replicates in vitro and induces immune response in mice. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2024 |
url |
https://doi.org/10.1371/journal.pntd.0012120 https://doaj.org/article/9b58470d827541d1a7b6317f99368d22 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 18, Iss 4, p e0012120 (2024) |
op_relation |
https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0012120&type=printable https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0012120 https://doaj.org/article/9b58470d827541d1a7b6317f99368d22 |
op_doi |
https://doi.org/10.1371/journal.pntd.0012120 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
18 |
container_issue |
4 |
container_start_page |
e0012120 |
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1809896093568204800 |