Stability of RNA virus attenuation approaches

Joan L. Kenney; Sara M. Volk; Jyotsna Pandya; Eryu Wang; Xiaodong Liang; Scott C. Weaver

doi:10.1016/j.vaccine.2011.01.055

Stability of RNA virus attenuation approaches

Joan L. Kenney, Sara M. Volk, Jyotsna Pandya, Eryu Wang, Xiaodong Liang, Scott C. Weaver

Microbiology And Immunology

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

The greatest risk from live-attenuated vaccines is reversion to virulence. Particular concerns arise for RNA viruses, which exhibit high mutation frequencies. We examined the stability of 3 attenuation strategies for the alphavirus, Venezuelan equine encephalitis virus (VEEV): a traditional, point mutation-dependent attenuation approach exemplified by TC-83; a rationally designed, targeted-mutation approach represented by V3526; and a chimeric vaccine, SIN/TC/ZPC. Our findings suggest that the chimeric strain combines the initial attenuation of TC-83 with the greater phenotypic stability of V3526, highlighting the importance of the both initial attenuation and stability for live-attenuated vaccines.

Original language	English (US)
Pages (from-to)	2230-2234
Number of pages	5
Journal	Vaccine
Volume	29
Issue number	12
DOIs	https://doi.org/10.1016/j.vaccine.2011.01.055
State	Published - 2011

Keywords

Alphavirus
RNA viruses
Vaccine stability
Venezuelan equine encephalitis virus

ASJC Scopus subject areas

Molecular Medicine
General Immunology and Microbiology
General Veterinary
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1016/j.vaccine.2011.01.055

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title = "Stability of RNA virus attenuation approaches",

abstract = "The greatest risk from live-attenuated vaccines is reversion to virulence. Particular concerns arise for RNA viruses, which exhibit high mutation frequencies. We examined the stability of 3 attenuation strategies for the alphavirus, Venezuelan equine encephalitis virus (VEEV): a traditional, point mutation-dependent attenuation approach exemplified by TC-83; a rationally designed, targeted-mutation approach represented by V3526; and a chimeric vaccine, SIN/TC/ZPC. Our findings suggest that the chimeric strain combines the initial attenuation of TC-83 with the greater phenotypic stability of V3526, highlighting the importance of the both initial attenuation and stability for live-attenuated vaccines.",

keywords = "Alphavirus, RNA viruses, Vaccine stability, Venezuelan equine encephalitis virus",

author = "Kenney, {Joan L.} and Volk, {Sara M.} and Jyotsna Pandya and Eryu Wang and Xiaodong Liang and Weaver, {Scott C.}",

note = "Funding Information: We thank Wenli Kang, Rubing Chen, and Mathilde Guerbois for technical assistance, and Nancy Davis, Robert Johnston, and Richard Kinney for providing cDNA clones for the V3526 and TC-83 vaccine strains. JLK was supported by a McLaughlin Endowment fellowship. SMV was supported by the NIH training grant T32 AI007536 . This work was supported by a grant from the National Institute of Allergy and Infectious Disease (NIAID) through the Western Regional Center of Excellence for Biodefense and Emerging Infectious Disease Research , National Institutes of Health (NIH) grant U54 AIO57156 .",

year = "2011",

doi = "10.1016/j.vaccine.2011.01.055",

language = "English (US)",

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AU - Kenney, Joan L.

AU - Volk, Sara M.

AU - Pandya, Jyotsna

AU - Wang, Eryu

AU - Liang, Xiaodong

AU - Weaver, Scott C.

N1 - Funding Information: We thank Wenli Kang, Rubing Chen, and Mathilde Guerbois for technical assistance, and Nancy Davis, Robert Johnston, and Richard Kinney for providing cDNA clones for the V3526 and TC-83 vaccine strains. JLK was supported by a McLaughlin Endowment fellowship. SMV was supported by the NIH training grant T32 AI007536 . This work was supported by a grant from the National Institute of Allergy and Infectious Disease (NIAID) through the Western Regional Center of Excellence for Biodefense and Emerging Infectious Disease Research , National Institutes of Health (NIH) grant U54 AIO57156 .

PY - 2011

Y1 - 2011

N2 - The greatest risk from live-attenuated vaccines is reversion to virulence. Particular concerns arise for RNA viruses, which exhibit high mutation frequencies. We examined the stability of 3 attenuation strategies for the alphavirus, Venezuelan equine encephalitis virus (VEEV): a traditional, point mutation-dependent attenuation approach exemplified by TC-83; a rationally designed, targeted-mutation approach represented by V3526; and a chimeric vaccine, SIN/TC/ZPC. Our findings suggest that the chimeric strain combines the initial attenuation of TC-83 with the greater phenotypic stability of V3526, highlighting the importance of the both initial attenuation and stability for live-attenuated vaccines.

AB - The greatest risk from live-attenuated vaccines is reversion to virulence. Particular concerns arise for RNA viruses, which exhibit high mutation frequencies. We examined the stability of 3 attenuation strategies for the alphavirus, Venezuelan equine encephalitis virus (VEEV): a traditional, point mutation-dependent attenuation approach exemplified by TC-83; a rationally designed, targeted-mutation approach represented by V3526; and a chimeric vaccine, SIN/TC/ZPC. Our findings suggest that the chimeric strain combines the initial attenuation of TC-83 with the greater phenotypic stability of V3526, highlighting the importance of the both initial attenuation and stability for live-attenuated vaccines.

KW - Alphavirus

KW - RNA viruses

KW - Vaccine stability

KW - Venezuelan equine encephalitis virus

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Stability of RNA virus attenuation approaches

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Keywords

ASJC Scopus subject areas

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