Inactivated Western Equine Encephalomyelitis Vaccine Propagated in Chick Embryo Cell Culture

Bartelloni, Peter J.; McKinney, Robert W.; Calia, Frank M.; Ramsburg, Helen H.; Cole, Francis E.

doi:10.4269/ajtmh.1971.20.146

Cited by 27 publications

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“…Our findings are consistent with previously published studies (Reitman et al, 1970; Bartelloni et al, 1971; Gruber J., 1971); Cole et al, 1974) in which either formalin or gamma irradiation was used for the preparation of inactivated alphavirus vaccines. In each of those studies, virus inactivation was confirmed by absence of plaque formation on mouse L-cell fibroblasts and/or absence of infectivity via IC inoculation of suckling mice.…”

Section: 0 Discussionsupporting

confidence: 93%

“…In particular, gamma radiation has been advocated as a means of obtaining a sterile, biologically active biotechnology products and the use of ionizing radiation has been explored in the production of noninfective antigens for vaccines (Eisenberg and Osterman, 1979; Datta et al, 2006 ). Several vaccines prepared against encephalitis viruses have employed either formalin (Maire et al, 1970; Bartelloni et al, 1971; Cole et al, 1974) or gamma irradiation (Reitman et al, 1970; Gruber, 1971). …”

Section: 0 Introductionmentioning

confidence: 99%

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A multisystem approach for development and evaluation of inactivated vaccines for Venezuelan equine encephalitis virus (VEEV)

Fine¹,

Jenkins²,

Martin³

et al. 2010

Journal of Virological Methods

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A multisystem approach was used to assess the efficiency of several methods for inactivation of Venezuelan equine encephalitis virus (VEEV) vaccine candidates. A combination of diverse assays (plaque, in vitro cytopathology and mouse neurovirulence) was used to verify virus inactivation, along with the use of a specific ELISA to measure retention of VEEV envelope glycoprotein epitopes in the development of several inactivated VEEV candidate vaccines derived from an attenuated strain of VEEV (V3526). Incubation of V3526 aliquots at temperatures in excess of 64°C for periods >30 minutes inactivated the virus, but substantially reduced VEEV specific monoclonal antibody binding of the inactivated material. In contrast, V3526 treated either with formalin at concentrations of 0.1% or 0.5% v/v for 4 or 24 hours, or irradiated with 50 kilogray gamma radiation rendered the virus noninfectious while retaining significant levels of monoclonal antibody binding. Loss of infectivity of both the formalin inactivated (fV3526) and gamma irradiated (gV3526) preparations was confirmed via five successive blind passages on BHK-21 cells. Similarly, loss of neurovirulence for fV3526 and gV3526 was demonstrated via intracerebral inoculation of suckling BALB/c mice. Excellent protection against subcutaneous challenge with VEEV IA/B Trinidad donkey strain was demonstrated using a two dose immunization regimen with either fV3526 or gV3526. The combination of in vitro and in vivo assays provides a practical approach to optimize manufacturing process parameters for development of other inactivated viral vaccines. KeywordsVenezuelan equine encephalitis virus (VEEV); Formalin inactivated vaccines; Gamma irradiated vaccines; Neurovirulence; Alphavirus Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript IntroductionOver the past eighty years Venezuelan equine encephalitis virus (VEEV), an alphavirus (family Togaviridae) transmitted by mosquitoes, has caused periodic outbreaks of febrile and neurological disease in equine and human populations in Central and South America, as well as North America (Mexico and Texas) [Weaver et al., 2004]. Due to its highly infectious nature by aerosol [de Mucha-Macias and Sanchez-Spindola, 1965;Dietz et al., 1979], VEEV is also considered a potential biological weapon amenable to use in warfare and terrorism (Smith et al., 1997;Weaver et al., 2004). To address the above health concerns, two vaccines were developed by the U.S. government during the 1960s and 1970s: TC-83 (McKi...

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confidence: 93%

Section: 0 Introductionmentioning

confidence: 99%

A multisystem approach for development and evaluation of inactivated vaccines for Venezuelan equine encephalitis virus (VEEV)

Fine¹,

Jenkins²,

Martin³

et al. 2010

Journal of Virological Methods

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“…However, TC-83 has a high potential for reversion and offers poor protection against enzootic subtypes of VEEV (2)(3)(4). Killed whole-virus vaccines have been developed for VEEV (C-84), WEEV, and EEEV by formalin treatment, and while these vaccines are safe, they also have a high failure rate for seroconversion (2,(5)(6)(7). All four vaccines have been used successfully for veterinary applications for several decades but are available only on a limited basis for human use.…”

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confidence: 99%

Combined Alphavirus Replicon Particle Vaccine Induces Durable and Cross-Protective Immune Responses against Equine Encephalitis Viruses

Reed

Glass

Bakken

et al. 2014

J Virol

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Alphavirus replicons were evaluated as potential vaccine candidates for Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), or eastern equine encephalitis virus (EEEV) when given individually or in combination (V/W/E) to mice or cynomolgus macaques. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in mice to their respective alphavirus. Protection from either subcutaneous or aerosol challenge with VEEV, WEEV, or EEEV was demonstrated out to 12 months after vaccination in mice. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in macaques and demonstrated good protection against aerosol challenge with an epizootic VEEV-IAB virus, Trinidad donkey. Similarly, the EEEV replicon and V/W/E combination vaccine elicited neutralizing antibodies against EEEV and protected against aerosol exposure to a North American variety of EEEV. Both the WEEV replicon and combination V/W/E vaccination, however, elicited poor neutralizing antibodies to WEEV in macaques, and the protection conferred was not as strong. These results demonstrate that a combination V/W/E vaccine is possible for protection against aerosol challenge and that cross-interference between the vaccines is minimal. IMPORTANCE Three related viruses belonging to the genus Alphavirus cause severe encephalitis in humans: Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), and eastern equine encephalitis virus (EEEV).Normally transmitted by mosquitoes, these viruses can cause disease when inhaled, so there is concern that these viruses could be used as biological weapons. Prior reports have suggested that vaccines for these three viruses might interfere with one another. We have developed a combined vaccine for Venezuelan equine encephalitis, western equine encephalitis, and eastern equine encephalitis expressing the surface proteins of all three viruses. In this report we demonstrate in both mice and macaques that this combined vaccine is safe, generates a strong immune response, and protects against aerosol challenge with the viruses that cause Venezuelan equine encephalitis, western equine encephalitis, and eastern equine encephalitis.

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“…The live-attenuated VEEV IND vaccine, TC-83, provides long-lasting immunity and protection from both subcutaneous and aerosol VEEV challenges; however, it causes significant adverse reactions in approximately 25% of recipients, and approximately 20% of recipients fail to develop a detectable neutralizing antibody response [ 11 , 12 ]. The formalin-inactivated VEEV IND vaccine derived from TC-83, C-84, and the formalin-inactivated WEEV and EEEV IND vaccines are well tolerated, but they require frequent boosting to elicit and maintain detectable neutralizing antibody responses in humans and have exhibited suboptimal protection against aerosol viral challenge in animal studies [ 13 – 15 ]. In addition, immune interference has been documented when the VEEV, WEEV, and EEEV IND vaccines are administered simultaneously or sequentially in humans [ 16 – 18 ].…”

Section: Introductionmentioning

confidence: 99%

A Multiagent Alphavirus DNA Vaccine Delivered by Intramuscular Electroporation Elicits Robust and Durable Virus-Specific Immune Responses in Mice and Rabbits and Completely Protects Mice against Lethal Venezuelan, Western, and Eastern Equine Encephalitis Virus Aerosol Challenges

Dupuy

Richards

Livingston

et al. 2018

Journal of Immunology Research

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There remains a need for vaccines that can safely and effectively protect against the biological threat agents Venezuelan (VEEV), western (WEEV), and eastern (EEEV) equine encephalitis virus. Previously, we demonstrated that a VEEV DNA vaccine that was optimized for increased antigen expression and delivered by intramuscular (IM) electroporation (EP) elicited robust and durable virus-specific antibody responses in multiple animal species and provided complete protection against VEEV aerosol challenge in mice and nonhuman primates. Here, we performed a comparative evaluation of the immunogenicity and protective efficacy of individual optimized VEEV, WEEV, and EEEV DNA vaccines with that of a 1 : 1 : 1 mixture of these vaccines, which we have termed the 3-EEV DNA vaccine, when delivered by IM EP. The individual DNA vaccines and the 3-EEV DNA vaccine elicited robust and durable virus-specific antibody responses in mice and rabbits and completely protected mice from homologous VEEV, WEEV, and EEEV aerosol challenges. Taken together, the results from these studies demonstrate that the individual VEEV, WEEV, and EEEV DNA vaccines and the 3-EEV DNA vaccine delivered by IM EP provide an effective means of eliciting protection against lethal encephalitic alphavirus infections in a murine model and represent viable next-generation vaccine candidates that warrant further development.

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Inactivated Western Equine Encephalomyelitis Vaccine Propagated in Chick Embryo Cell Culture

Cited by 27 publications

References 0 publications

A multisystem approach for development and evaluation of inactivated vaccines for Venezuelan equine encephalitis virus (VEEV)

A multisystem approach for development and evaluation of inactivated vaccines for Venezuelan equine encephalitis virus (VEEV)

Combined Alphavirus Replicon Particle Vaccine Induces Durable and Cross-Protective Immune Responses against Equine Encephalitis Viruses

A Multiagent Alphavirus DNA Vaccine Delivered by Intramuscular Electroporation Elicits Robust and Durable Virus-Specific Immune Responses in Mice and Rabbits and Completely Protects Mice against Lethal Venezuelan, Western, and Eastern Equine Encephalitis Virus Aerosol Challenges

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