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Comparison of uridine and N1-methylpseudouridine mRNA platforms in development of an Andes virus vaccine
by
Weidner, Nicole G.
, Kuzmin, Ivan V.
, Hernandez, Keziah R.
, Wasdin, Perry T.
, Garcia-Blanco, Mariano A.
, Popov, Vsevolod
, Engdahl, Taylor B.
, Hill, Kharighan
, Crowe, James E.
, Pruitt, Layne
, Mire, Chad
, Moon, Woohyun J.
, Soto Acosta, Ruben
, Bukreyev, Alexander
, Gonzales, Kristyn A.
, Abbott, Robert K.
, Georgiev, Ivelin S.
, Kedarinath, Kritika
in
13
/ 13/1
/ 13/106
/ 13/109
/ 13/21
/ 13/31
/ 13/51
/ 13/62
/ 38
/ 38/23
/ 631/250/2152/2153/1982
/ 631/326/590/2293
/ 631/326/596
/ Animals
/ Antibodies
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - immunology
/ B-Lymphocytes - immunology
/ Cell activation
/ Cricetinae
/ Female
/ Females
/ Gene expression
/ Gene sequencing
/ Germinal Center - immunology
/ Germinal centers
/ Glycoproteins
/ Hamsters
/ Hemorrhagic Fever, American - immunology
/ Hemorrhagic Fever, American - prevention & control
/ Hemorrhagic Fever, American - virology
/ Humanities and Social Sciences
/ Humans
/ Immune response
/ Immune system
/ Immunization
/ Immunogenicity
/ Lethal dose
/ Lymphocytes B
/ Mesocricetus
/ Mice
/ mRNA
/ mRNA Vaccines
/ multidisciplinary
/ Orthohantavirus - genetics
/ Orthohantavirus - immunology
/ Pseudouridine - immunology
/ RNA modification
/ RNA, Messenger - genetics
/ RNA, Messenger - immunology
/ RNA, Messenger - metabolism
/ RNA, Viral - genetics
/ RNA, Viral - immunology
/ Rodents
/ Science
/ Science (multidisciplinary)
/ Segments
/ Uridine
/ Vaccine Development
/ Vaccines
/ Viral Vaccines - administration & dosage
/ Viral Vaccines - immunology
/ Viruses
2024
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Comparison of uridine and N1-methylpseudouridine mRNA platforms in development of an Andes virus vaccine
by
Weidner, Nicole G.
, Kuzmin, Ivan V.
, Hernandez, Keziah R.
, Wasdin, Perry T.
, Garcia-Blanco, Mariano A.
, Popov, Vsevolod
, Engdahl, Taylor B.
, Hill, Kharighan
, Crowe, James E.
, Pruitt, Layne
, Mire, Chad
, Moon, Woohyun J.
, Soto Acosta, Ruben
, Bukreyev, Alexander
, Gonzales, Kristyn A.
, Abbott, Robert K.
, Georgiev, Ivelin S.
, Kedarinath, Kritika
in
13
/ 13/1
/ 13/106
/ 13/109
/ 13/21
/ 13/31
/ 13/51
/ 13/62
/ 38
/ 38/23
/ 631/250/2152/2153/1982
/ 631/326/590/2293
/ 631/326/596
/ Animals
/ Antibodies
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - immunology
/ B-Lymphocytes - immunology
/ Cell activation
/ Cricetinae
/ Female
/ Females
/ Gene expression
/ Gene sequencing
/ Germinal Center - immunology
/ Germinal centers
/ Glycoproteins
/ Hamsters
/ Hemorrhagic Fever, American - immunology
/ Hemorrhagic Fever, American - prevention & control
/ Hemorrhagic Fever, American - virology
/ Humanities and Social Sciences
/ Humans
/ Immune response
/ Immune system
/ Immunization
/ Immunogenicity
/ Lethal dose
/ Lymphocytes B
/ Mesocricetus
/ Mice
/ mRNA
/ mRNA Vaccines
/ multidisciplinary
/ Orthohantavirus - genetics
/ Orthohantavirus - immunology
/ Pseudouridine - immunology
/ RNA modification
/ RNA, Messenger - genetics
/ RNA, Messenger - immunology
/ RNA, Messenger - metabolism
/ RNA, Viral - genetics
/ RNA, Viral - immunology
/ Rodents
/ Science
/ Science (multidisciplinary)
/ Segments
/ Uridine
/ Vaccine Development
/ Vaccines
/ Viral Vaccines - administration & dosage
/ Viral Vaccines - immunology
/ Viruses
2024
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Comparison of uridine and N1-methylpseudouridine mRNA platforms in development of an Andes virus vaccine
by
Weidner, Nicole G.
, Kuzmin, Ivan V.
, Hernandez, Keziah R.
, Wasdin, Perry T.
, Garcia-Blanco, Mariano A.
, Popov, Vsevolod
, Engdahl, Taylor B.
, Hill, Kharighan
, Crowe, James E.
, Pruitt, Layne
, Mire, Chad
, Moon, Woohyun J.
, Soto Acosta, Ruben
, Bukreyev, Alexander
, Gonzales, Kristyn A.
, Abbott, Robert K.
, Georgiev, Ivelin S.
, Kedarinath, Kritika
in
13
/ 13/1
/ 13/106
/ 13/109
/ 13/21
/ 13/31
/ 13/51
/ 13/62
/ 38
/ 38/23
/ 631/250/2152/2153/1982
/ 631/326/590/2293
/ 631/326/596
/ Animals
/ Antibodies
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - immunology
/ B-Lymphocytes - immunology
/ Cell activation
/ Cricetinae
/ Female
/ Females
/ Gene expression
/ Gene sequencing
/ Germinal Center - immunology
/ Germinal centers
/ Glycoproteins
/ Hamsters
/ Hemorrhagic Fever, American - immunology
/ Hemorrhagic Fever, American - prevention & control
/ Hemorrhagic Fever, American - virology
/ Humanities and Social Sciences
/ Humans
/ Immune response
/ Immune system
/ Immunization
/ Immunogenicity
/ Lethal dose
/ Lymphocytes B
/ Mesocricetus
/ Mice
/ mRNA
/ mRNA Vaccines
/ multidisciplinary
/ Orthohantavirus - genetics
/ Orthohantavirus - immunology
/ Pseudouridine - immunology
/ RNA modification
/ RNA, Messenger - genetics
/ RNA, Messenger - immunology
/ RNA, Messenger - metabolism
/ RNA, Viral - genetics
/ RNA, Viral - immunology
/ Rodents
/ Science
/ Science (multidisciplinary)
/ Segments
/ Uridine
/ Vaccine Development
/ Vaccines
/ Viral Vaccines - administration & dosage
/ Viral Vaccines - immunology
/ Viruses
2024
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Comparison of uridine and N1-methylpseudouridine mRNA platforms in development of an Andes virus vaccine
Journal Article
Comparison of uridine and N1-methylpseudouridine mRNA platforms in development of an Andes virus vaccine
2024
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Overview
The rodent-borne Andes virus (ANDV) causes a severe disease in humans. We developed an ANDV mRNA vaccine based on the M segment of the viral genome, either with regular uridine (U-mRNA) or N1-methylpseudouridine (m1Ψ-mRNA). Female mice immunized by m1Ψ-mRNA developed slightly greater germinal center (GC) responses than U-mRNA-immunized mice. Single cell RNA and BCR sequencing of the GC B cells revealed similar levels of activation, except an additional cluster of cells exhibiting interferon response in animals vaccinated with U-mRNA but not m1Ψ-mRNA. Similar immunoglobulin class-switching and somatic hypermutations were observed in response to the vaccines. Female Syrian hamsters were immunized via a prime–boost regimen with two doses of each vaccine. The titers of glycoprotein-binding antibodies were greater for U-mRNA construct than for m1Ψ-mRNA construct; however, the titers of ANDV-neutralizing antibodies were similar. Vaccinated animals were challenged with a lethal dose of ANDV, along with a naïve control group. All control animals and two animals vaccinated with a lower dose of m1Ψ-mRNA succumbed to infection whereas other vaccinated animals survived without evidence of virus replication. The data demonstrate the development of a protective vaccine against ANDV and the lack of a substantial effect of m1Ψ modification on immunogenicity and protection in rodents.
Modified nucleosides are often used in mRNA vaccines and can affect protein expression and immunogenicity. Here, the authors compare M segment based Andes virus mRNA vaccines, either with regular uridine or N1-methylpseudouridine, and characterize immune response and protection in rodents.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/1
/ 13/106
/ 13/109
/ 13/21
/ 13/31
/ 13/51
/ 13/62
/ 38
/ 38/23
/ Animals
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - immunology
/ Female
/ Females
/ Germinal Center - immunology
/ Hamsters
/ Hemorrhagic Fever, American - immunology
/ Hemorrhagic Fever, American - prevention & control
/ Hemorrhagic Fever, American - virology
/ Humanities and Social Sciences
/ Humans
/ Mice
/ mRNA
/ Orthohantavirus - immunology
/ Rodents
/ Science
/ Segments
/ Uridine
/ Vaccines
/ Viral Vaccines - administration & dosage
/ Viruses
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