Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single Dose
Venezuelan equine encephalitis virus (VEEV) is a re-emerging virus of human, agriculture, and bioweapon threat importance. No FDA-approved treatment is available to combat Venezuelan equine encephalitis in humans, prompting the need to create a vaccine that is safe, efficacious, and cannot be replic...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-09-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/8/3/497 |
| _version_ | 1827707050049667072 |
|---|---|
| author | Shannan L. Rossi Kasi E. Russell-Lodrigue Kenneth S. Plante Nicholas A. Bergren Rodion Gorchakov Chad J. Roy Scott C. Weaver |
| author_facet | Shannan L. Rossi Kasi E. Russell-Lodrigue Kenneth S. Plante Nicholas A. Bergren Rodion Gorchakov Chad J. Roy Scott C. Weaver |
| author_sort | Shannan L. Rossi |
| collection | DOAJ |
| description | Venezuelan equine encephalitis virus (VEEV) is a re-emerging virus of human, agriculture, and bioweapon threat importance. No FDA-approved treatment is available to combat Venezuelan equine encephalitis in humans, prompting the need to create a vaccine that is safe, efficacious, and cannot be replicated in the mosquito vector. Here we describe the use of a serotype ID VEEV (ZPC-738) vaccine with an internal ribosome entry site (IRES) to alter gene expression patterns. This ZPC/IRES vaccine was genetically engineered in two ways based on the position of the IRES insertion to create a vaccine that is safe and efficacious. After a single dose, both versions of the ZPC/IRES vaccine elicited neutralizing antibody responses in mice and non-human primates after a single dose, with more robust responses produced by version 2. Further, all mice and primates were protected from viremia following VEEV challenge. These vaccines were also safer in neonatal mice than the current investigational new drug vaccine, TC-83. These results show that IRES-based attenuation of alphavirus genomes consistently produce promising vaccine candidates, with VEEV/IRES version 2 showing promise for further development. |
| first_indexed | 2024-03-10T16:38:09Z |
| format | Article |
| id | doaj.art-c0046c07980d447fb988bbbc01ca40f1 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T16:38:09Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-c0046c07980d447fb988bbbc01ca40f12023-11-20T12:16:43ZengMDPI AGVaccines2076-393X2020-09-018349710.3390/vaccines8030497Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single DoseShannan L. Rossi0Kasi E. Russell-Lodrigue1Kenneth S. Plante2Nicholas A. Bergren3Rodion Gorchakov4Chad J. Roy5Scott C. Weaver6Department of Pathology and Microbiology and Immunology, Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USATulane National Primate Research Center, Covington, LA 70433, USADepartment of Microbiology and Immunology and World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Health, Safety and Environment, King Abdullah University of Science and Technology, Thuwal 23955, Saudi ArabiaTulane National Primate Research Center, Covington, LA 70433, USAWorld Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX 77555, USAVenezuelan equine encephalitis virus (VEEV) is a re-emerging virus of human, agriculture, and bioweapon threat importance. No FDA-approved treatment is available to combat Venezuelan equine encephalitis in humans, prompting the need to create a vaccine that is safe, efficacious, and cannot be replicated in the mosquito vector. Here we describe the use of a serotype ID VEEV (ZPC-738) vaccine with an internal ribosome entry site (IRES) to alter gene expression patterns. This ZPC/IRES vaccine was genetically engineered in two ways based on the position of the IRES insertion to create a vaccine that is safe and efficacious. After a single dose, both versions of the ZPC/IRES vaccine elicited neutralizing antibody responses in mice and non-human primates after a single dose, with more robust responses produced by version 2. Further, all mice and primates were protected from viremia following VEEV challenge. These vaccines were also safer in neonatal mice than the current investigational new drug vaccine, TC-83. These results show that IRES-based attenuation of alphavirus genomes consistently produce promising vaccine candidates, with VEEV/IRES version 2 showing promise for further development.https://www.mdpi.com/2076-393X/8/3/497Venezuelan equine encephalitis virusvaccineinternal ribosome entry siteprimates |
| spellingShingle | Shannan L. Rossi Kasi E. Russell-Lodrigue Kenneth S. Plante Nicholas A. Bergren Rodion Gorchakov Chad J. Roy Scott C. Weaver Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single Dose Vaccines Venezuelan equine encephalitis virus vaccine internal ribosome entry site primates |
| title | Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single Dose |
| title_full | Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single Dose |
| title_fullStr | Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single Dose |
| title_full_unstemmed | Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single Dose |
| title_short | Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single Dose |
| title_sort | rationally attenuated vaccines for venezuelan equine encephalitis protect against epidemic strains with a single dose |
| topic | Venezuelan equine encephalitis virus vaccine internal ribosome entry site primates |
| url | https://www.mdpi.com/2076-393X/8/3/497 |
| work_keys_str_mv | AT shannanlrossi rationallyattenuatedvaccinesforvenezuelanequineencephalitisprotectagainstepidemicstrainswithasingledose AT kasierusselllodrigue rationallyattenuatedvaccinesforvenezuelanequineencephalitisprotectagainstepidemicstrainswithasingledose AT kennethsplante rationallyattenuatedvaccinesforvenezuelanequineencephalitisprotectagainstepidemicstrainswithasingledose AT nicholasabergren rationallyattenuatedvaccinesforvenezuelanequineencephalitisprotectagainstepidemicstrainswithasingledose AT rodiongorchakov rationallyattenuatedvaccinesforvenezuelanequineencephalitisprotectagainstepidemicstrainswithasingledose AT chadjroy rationallyattenuatedvaccinesforvenezuelanequineencephalitisprotectagainstepidemicstrainswithasingledose AT scottcweaver rationallyattenuatedvaccinesforvenezuelanequineencephalitisprotectagainstepidemicstrainswithasingledose |