The Western Equine Encephalitis Lyophilized, Inactivated Vaccine: An Update on Safety and Immunogenicity
BackgroundWestern Equine Encephalitis (WEE) is a naturally acquired infection and potentially devastating bioweapon, with no specific human countermeasures. An experimental inactivated Western Equine Encephalitis Vaccine (WEEV; WEE TSI-GSD 210) has been used under an IND (investigational New Drug) p...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.555464/full |
| _version_ | 1819072519084179456 |
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| author | Maryam Keshtkar-Jahromi Ronald B. Reisler Jeannine M. Haller Denise P. Clizbe Robert G. Rivard Anthony P. Cardile Benjamin C. Pierson Sarah Norris David Saunders Phillip R. Pittman |
| author_facet | Maryam Keshtkar-Jahromi Ronald B. Reisler Jeannine M. Haller Denise P. Clizbe Robert G. Rivard Anthony P. Cardile Benjamin C. Pierson Sarah Norris David Saunders Phillip R. Pittman |
| author_sort | Maryam Keshtkar-Jahromi |
| collection | DOAJ |
| description | BackgroundWestern Equine Encephalitis (WEE) is a naturally acquired infection and potentially devastating bioweapon, with no specific human countermeasures. An experimental inactivated Western Equine Encephalitis Vaccine (WEEV; WEE TSI-GSD 210) has been used under an IND (investigational New Drug) protocol at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) since 1976.MethodsOver 24 years from 1987 to 2011, 876 subjects received 3 primary vaccine doses under 3 studies with 1,537 booster doses administered (FY87-8, phase 2, laboratory workers, vaccine lots 1-81-1, 1-81-2, and 2-1-91; FY99-12, phase 2 laboratory workers, lot 2-1-91; and FY09-02, phase 1 healthy volunteer, lot 3-1-92). Post-vaccination safety and immunogenicity [plaque reduction neutralization test 80% (PRNT80) > 1:40] were analyzed.ResultsOverall PRNT80 response to the primary series in FY87-8 was 42% (326/770) but dropped to 16% (14/87) in FY99-12, prompting study FY09-02, which achieved 89% (17/19). The first booster response rate was 68% (814/1194) in FY87-8, 53% (171/324) in FY99-12, and 100% (10/10) in FY09-02. The majority of definitely related adverse reactions (AEs) were mild and local with no definitely related serious AEs. No laboratory acquired WEE infection was documented during this period despite 4 reported exposures in vaccinated subjects.ConclusionThe TSI-GSD 210 WEE vaccine was immunogenic, safe and well tolerated. Use of this vaccine could be considered in an emergency setting. Despite decades of safe and effective use under IND, full licensure is not planned due to manufacturing constraints, and a strategic decision to develop alternatives.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier NCT01159561. |
| first_indexed | 2024-12-21T17:39:01Z |
| format | Article |
| id | doaj.art-1499ca956a2c49ac9c04a21b12633e5f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T17:39:01Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1499ca956a2c49ac9c04a21b12633e5f2022-12-21T18:55:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-11-011110.3389/fimmu.2020.555464555464The Western Equine Encephalitis Lyophilized, Inactivated Vaccine: An Update on Safety and ImmunogenicityMaryam Keshtkar-Jahromi0Ronald B. Reisler1Jeannine M. Haller2Denise P. Clizbe3Robert G. Rivard4Anthony P. Cardile5Benjamin C. Pierson6Sarah Norris7David Saunders8Phillip R. Pittman9Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDivision of Medicine, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, United StatesDivision of Medicine, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, United StatesDivision of Medicine, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, United StatesDivision of Medicine, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, United StatesDivision of Medicine, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, United StatesDivision of Medicine, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, United StatesDivision of Medicine, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, United StatesDivision of Medicine, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, United StatesDivision of Medicine, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, United StatesBackgroundWestern Equine Encephalitis (WEE) is a naturally acquired infection and potentially devastating bioweapon, with no specific human countermeasures. An experimental inactivated Western Equine Encephalitis Vaccine (WEEV; WEE TSI-GSD 210) has been used under an IND (investigational New Drug) protocol at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) since 1976.MethodsOver 24 years from 1987 to 2011, 876 subjects received 3 primary vaccine doses under 3 studies with 1,537 booster doses administered (FY87-8, phase 2, laboratory workers, vaccine lots 1-81-1, 1-81-2, and 2-1-91; FY99-12, phase 2 laboratory workers, lot 2-1-91; and FY09-02, phase 1 healthy volunteer, lot 3-1-92). Post-vaccination safety and immunogenicity [plaque reduction neutralization test 80% (PRNT80) > 1:40] were analyzed.ResultsOverall PRNT80 response to the primary series in FY87-8 was 42% (326/770) but dropped to 16% (14/87) in FY99-12, prompting study FY09-02, which achieved 89% (17/19). The first booster response rate was 68% (814/1194) in FY87-8, 53% (171/324) in FY99-12, and 100% (10/10) in FY09-02. The majority of definitely related adverse reactions (AEs) were mild and local with no definitely related serious AEs. No laboratory acquired WEE infection was documented during this period despite 4 reported exposures in vaccinated subjects.ConclusionThe TSI-GSD 210 WEE vaccine was immunogenic, safe and well tolerated. Use of this vaccine could be considered in an emergency setting. Despite decades of safe and effective use under IND, full licensure is not planned due to manufacturing constraints, and a strategic decision to develop alternatives.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier NCT01159561.https://www.frontiersin.org/articles/10.3389/fimmu.2020.555464/fullvaccineWestern Equine Encephalitisimmunogenicityclinical trialinactivated |
| spellingShingle | Maryam Keshtkar-Jahromi Ronald B. Reisler Jeannine M. Haller Denise P. Clizbe Robert G. Rivard Anthony P. Cardile Benjamin C. Pierson Sarah Norris David Saunders Phillip R. Pittman The Western Equine Encephalitis Lyophilized, Inactivated Vaccine: An Update on Safety and Immunogenicity Frontiers in Immunology vaccine Western Equine Encephalitis immunogenicity clinical trial inactivated |
| title | The Western Equine Encephalitis Lyophilized, Inactivated Vaccine: An Update on Safety and Immunogenicity |
| title_full | The Western Equine Encephalitis Lyophilized, Inactivated Vaccine: An Update on Safety and Immunogenicity |
| title_fullStr | The Western Equine Encephalitis Lyophilized, Inactivated Vaccine: An Update on Safety and Immunogenicity |
| title_full_unstemmed | The Western Equine Encephalitis Lyophilized, Inactivated Vaccine: An Update on Safety and Immunogenicity |
| title_short | The Western Equine Encephalitis Lyophilized, Inactivated Vaccine: An Update on Safety and Immunogenicity |
| title_sort | western equine encephalitis lyophilized inactivated vaccine an update on safety and immunogenicity |
| topic | vaccine Western Equine Encephalitis immunogenicity clinical trial inactivated |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.555464/full |
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