Chikungunya vaccine candidate is highly attenuated and protects nonhuman primates against telemetrically monitored disease following a single dose

Chad J. Roy; A. Paige Adams; Eryu Wang; Kenneth Plante; Rodion Gorchakov; Robert L. Seymour; Heather Vinet-Oliphant; Scott C. Weaver

doi:10.1093/infdis/jiu014

Chikungunya vaccine candidate is highly attenuated and protects nonhuman primates against telemetrically monitored disease following a single dose

Chad J. Roy, A. Paige Adams, Eryu Wang, Kenneth Plante, Rodion Gorchakov, Robert L. Seymour, Heather Vinet-Oliphant, Scott C. Weaver

Microbiology And Immunology

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

65 Scopus citations

Abstract

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes major epidemics of rash, fever, and debilitating arthritis. Currently, there are no vaccines or antivirals available for prevention or treatment. We therefore generated 2 live-attenuated vaccine candidates based on the insertion of a picornavirus internal ribosome entry site (IRES) sequence into the genome of CHIKV. Vaccination of cynomolgus macaques with a single dose of either vaccine produced no signs of disease but was highly immunogenic. After challenge with a subcutaneous inoculation of wild-type CHIKV, both vaccine candidates prevented the development of detectable viremia. Protected animals also exhibited no significant changes in core body temperature or cardiovascular rhythm, whereas sham-vaccinated animals showed hyperthermia, followed by sustained hypothermia, as well as significant changes in heart rate. These CHIKV/IRES vaccine candidates appear to be safe and efficacious, supporting their strong potential as human vaccines to protect against CHIKV infection and reduce transmission and further spread.

Original language	English (US)
Pages (from-to)	1891-1899
Number of pages	9
Journal	Journal of Infectious Diseases
Volume	209
Issue number	12
DOIs	https://doi.org/10.1093/infdis/jiu014
State	Published - Jun 15 2014

Keywords

Chikungunya virus
nonhuman primates
viral vaccine

ASJC Scopus subject areas

General Medicine

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10.1093/infdis/jiu014

Cite this

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title = "Chikungunya vaccine candidate is highly attenuated and protects nonhuman primates against telemetrically monitored disease following a single dose",

abstract = "Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes major epidemics of rash, fever, and debilitating arthritis. Currently, there are no vaccines or antivirals available for prevention or treatment. We therefore generated 2 live-attenuated vaccine candidates based on the insertion of a picornavirus internal ribosome entry site (IRES) sequence into the genome of CHIKV. Vaccination of cynomolgus macaques with a single dose of either vaccine produced no signs of disease but was highly immunogenic. After challenge with a subcutaneous inoculation of wild-type CHIKV, both vaccine candidates prevented the development of detectable viremia. Protected animals also exhibited no significant changes in core body temperature or cardiovascular rhythm, whereas sham-vaccinated animals showed hyperthermia, followed by sustained hypothermia, as well as significant changes in heart rate. These CHIKV/IRES vaccine candidates appear to be safe and efficacious, supporting their strong potential as human vaccines to protect against CHIKV infection and reduce transmission and further spread.",

keywords = "Chikungunya virus, nonhuman primates, viral vaccine",

author = "Roy, {Chad J.} and Adams, {A. Paige} and Eryu Wang and Kenneth Plante and Rodion Gorchakov and Seymour, {Robert L.} and Heather Vinet-Oliphant and Weaver, {Scott C.}",

note = "Funding Information: Financial support. 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 (WRCE), National Institutes of Health (NIH) grant U54 AI057156. A. P. A. was supported by a NIH K08 grant AI077796, and R. L. S. was supported by a NIH T32 grant AI007536. This work was supported in part through the NIH/OD grant OD-011104-51 (Tulane National Primate Research Center Base grant). Potential conflicts of interest. All authors: No reported conflicts.",

year = "2014",

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doi = "10.1093/infdis/jiu014",

language = "English (US)",

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T1 - Chikungunya vaccine candidate is highly attenuated and protects nonhuman primates against telemetrically monitored disease following a single dose

AU - Roy, Chad J.

AU - Adams, A. Paige

AU - Wang, Eryu

AU - Plante, Kenneth

AU - Gorchakov, Rodion

AU - Seymour, Robert L.

AU - Vinet-Oliphant, Heather

AU - Weaver, Scott C.

N1 - Funding Information: Financial support. 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 (WRCE), National Institutes of Health (NIH) grant U54 AI057156. A. P. A. was supported by a NIH K08 grant AI077796, and R. L. S. was supported by a NIH T32 grant AI007536. This work was supported in part through the NIH/OD grant OD-011104-51 (Tulane National Primate Research Center Base grant). Potential conflicts of interest. All authors: No reported conflicts.

PY - 2014/6/15

Y1 - 2014/6/15

N2 - Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes major epidemics of rash, fever, and debilitating arthritis. Currently, there are no vaccines or antivirals available for prevention or treatment. We therefore generated 2 live-attenuated vaccine candidates based on the insertion of a picornavirus internal ribosome entry site (IRES) sequence into the genome of CHIKV. Vaccination of cynomolgus macaques with a single dose of either vaccine produced no signs of disease but was highly immunogenic. After challenge with a subcutaneous inoculation of wild-type CHIKV, both vaccine candidates prevented the development of detectable viremia. Protected animals also exhibited no significant changes in core body temperature or cardiovascular rhythm, whereas sham-vaccinated animals showed hyperthermia, followed by sustained hypothermia, as well as significant changes in heart rate. These CHIKV/IRES vaccine candidates appear to be safe and efficacious, supporting their strong potential as human vaccines to protect against CHIKV infection and reduce transmission and further spread.

AB - Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes major epidemics of rash, fever, and debilitating arthritis. Currently, there are no vaccines or antivirals available for prevention or treatment. We therefore generated 2 live-attenuated vaccine candidates based on the insertion of a picornavirus internal ribosome entry site (IRES) sequence into the genome of CHIKV. Vaccination of cynomolgus macaques with a single dose of either vaccine produced no signs of disease but was highly immunogenic. After challenge with a subcutaneous inoculation of wild-type CHIKV, both vaccine candidates prevented the development of detectable viremia. Protected animals also exhibited no significant changes in core body temperature or cardiovascular rhythm, whereas sham-vaccinated animals showed hyperthermia, followed by sustained hypothermia, as well as significant changes in heart rate. These CHIKV/IRES vaccine candidates appear to be safe and efficacious, supporting their strong potential as human vaccines to protect against CHIKV infection and reduce transmission and further spread.

KW - Chikungunya virus

KW - nonhuman primates

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Chikungunya vaccine candidate is highly attenuated and protects nonhuman primates against telemetrically monitored disease following a single dose

Abstract

Keywords

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