Isolation of the Vaccine Strain of Venezuelan Equine Encephalomyelitis Virus From Mosquitoes in Louisiana

Pedersen, Carl E.; Robinson, David M.; Cole, Francis E.

doi:10.1093/oxfordjournals.aje.a121416

Cited by 60 publications

(45 citation statements)

References 5 publications

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“…This was documented by the isolation of TC-83, the current IND live-attenuated VEE virus vaccine, from fieldcollected mosquitoes after TC-83 was used to vaccinate equines during an outbreak of VEE in the early 1970s. 11 Aedes taeniorhynchus was selected for these studies because it was incriminated as a vector in several outbreaks of VEE. 6,12,13 In addition to being a competent laboratory vector, 7,14 it is a common mosquito that readily feeds on humans throughout its range.…”

Section: Discussionmentioning

confidence: 99%

Limited potential for mosquito transmission of genetically engineered, live-attenuated Venezuelan equine encephalitis virus vaccine candidates.

Turell¹,

Kondig²,

Ludwig³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. In an attempt to improve the current live-attenuated vaccine (TC-83) for Venezuelan equine encephalitis (VEE), specific mutations associated with attenuation of VEE virus in rodent models were identified. These mutations were inserted into full-length cDNA clones of the Trinidad donkey strain of VEE virus by site-directed mutagenesis, and isogenic virus strains with these mutations were recovered after transfection of baby hamster kidney cells with infectious RNA. We evaluated 10 of these strains for their ability to replicate in and be transmitted by Aedes taeniorhynchus, a natural vector of epizootic VEE virus. Two vaccine candidates, one containing a deletion of the PE2 furin cleavage site, the other a combination of three separate point mutations in the E2 glycoprotein, replicated in mosquitoes and were transmitted to hamsters significantly less efficiently than was either parental (wild type) VEE virus or TC-83 virus. Although the attenuated strains were transmitted to hamsters by mosquitoes, after intrathoracic inoculation, there was no evidence of reversion to a virulent phenotype. The mutations that resulted in less efficient replication in, or transmission by, mosquitoes should enhance vaccine safety and reduce the possibility of environmental spread to unintentional hosts.The current investigational new drug (IND) vaccine (TC-83) for Venezuelan equine encephalitis (VEE) strain IAB virus is a live-attenuated virus that causes reactogenicity in 20% of recipients and fails to elicit a positive seroresponse in 20% of recipients. 1 Current efforts to develop an improved live-attenuated vaccine for VEE identified specific mutations associated with attenuation of VEE virus in rodent models. 2-4 These attenuating mutations have been inserted into a fulllength cDNA clone of wild-type VEE virus (IAB) to produce selected isogenic strains containing one or more attenuating mutations. These attenuated strains are currently being evaluated for their potential as a live-attenuated VEE virus vaccine.Live-attenuated vaccines typically offer many advantages over inactivated immunogens (e.g., single immunization, more efficient induction of mucosal immunity, longer duration of immunity). However, live arbovirus vaccines have the potential to be transmitted to secondary hosts, and may revert to a more virulent virus. This reversion to virulence could occur in either the vertebrate or the arthropod host. Thus, we examined VEE virus strains that contained attenuating mutations that might be included in a live-attenuated vaccine for their ability to infect and be transmitted by mosquitoes. In addition, we evaluated these vaccine candidates for reversion to a more virulent phenotype after intrathoracic inoculation of Aedes taeniorhynchus mosquitoes. MATERIALS AND METHODS Mosquitoes. Two laboratory strains of Ae. taeniorhynchus, Vero Beach and Medical and Veterinary EntomologyResearch Laboratory (MAVERL), were used during these studies. Both of these strains have been in colonies for more than 30 years and are derive...

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Section: Discussionmentioning

confidence: 99%

Limited potential for mosquito transmission of genetically engineered, live-attenuated Venezuelan equine encephalitis virus vaccine candidates.

Turell¹,

Kondig²,

Ludwig³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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“…This is the first time that altered vector infectivity has been reported for alphaviruses. While TC-83 is an effective immunogen for eliciting protective VEE virus antibody, it has been isolated from mosquito vectors following horse vaccination (Pedersen et al, 1972). Our ability to identify non-lethal changes in the E2 glycoprotein that block virus dissemination from mosquito midgut to the brain is an important observation for alphavirus vaccine design.…”

Section: Discussionmentioning

confidence: 99%

A single amino acid change in the E2 glycoprotein of Venezuelan equine encephalitis virus affects replication and dissemination in Aedes aegypti mosquitoes

Woodward

Miller

Beaty

et al. 1991

Journal of General Virology

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Four monoclonal antibody-resistant variants (MARVs) of Venezuelan equine encephalitis (VEE) virus were used to study mosquito-virus interactions.In vitro experiments using an Aedes albopictus cell line, C6/36, demonstrated that an amino acid change in the glycoprotein E2 h epitope (MARV 1A3B-7) decreased virus growth when compared with the wild-type, Trinidad donkey virus, and its vaccine derivative, TC-83. The MARVs replicated as efficiently as the parent virus when inoculated into Aedes aegypti mosquitoes, but MARV 1A3B-7 was restricted in its ability to infect and disseminate from the midgut following oral infection. These results demonstrate that a single amino acid change in the E2 glycoprotein can affect the ability of VEE virus to replicate and disseminate in Ae. aegypti mosquitoes.

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“…9 Additionally, viremias in horses, mules, and donkeys may be sufficient to infect mosquitoes that could potentially transmit virus to other susceptible hosts. 10 Finally, there is some evidence from accidental laboratory exposures that the vaccine does not adequately protect against infection from heterologous VEE virus subtypes (Jahrling PB, unpublished data). 11 A new-generation, live-attenuated VEE vaccine, currently under development, is being prepared to overcome the problems and limitations associated with TC-83.…”

Section: Introductionmentioning

confidence: 99%

Comparative neurovirulence of attenuated and non-attenuated strains of Venezuelan equine encephalitis virus in mice.

Ludwig

Turell²,

Peter³

et al. 2001

The American Journal of Tropical Medicine and Hygiene

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Abstract. A candidate live-attenuated virus vaccine for protection against Venezuelan equine encephalitis (VEE) (designated V3526) was tested in mice to measure the magnitude, duration, and kinetics of virus replication in the blood and the central nervous system and its phenotypic stability after multiple passages in mice and cell culture. All results were compared to parallel experiments with parental virus and the existing VEE virus vaccine, TC-83. Maximum virus titers in the brains of V3526-inoculated mice were between 10-and 100-fold less than those observed in brains of mice inoculated intracranially (ic) with either the parental virus or TC-83. Neither V3526 nor TC-83 was lethal in BALB/c mice inoculated ic. However, mice inoculated with TC-83 developed acute symptoms lasting at least 14 days. In contrast, ic inoculation of TC-83 was uniformly lethal for C3H/HeN mice. V3526 was avirulent in both BALB/c and C3H/HeN mice after ic inoculation. The virulence characteristics of V3526 remained unchanged after five serial ic passages in mouse brains or after five cell culture passages. Finally, pathologic changes induced after ic inoculation of V3526 were consistently less severe and of shorter duration than those observed in TC-83-inoculated mice. Based on these results, V3526 is stable and appears to be significantly less neurovirulent in mice than TC-83.

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Isolation of the Vaccine Strain of Venezuelan Equine Encephalomyelitis Virus From Mosquitoes in Louisiana

Cited by 60 publications

References 5 publications

Limited potential for mosquito transmission of genetically engineered, live-attenuated Venezuelan equine encephalitis virus vaccine candidates.

Limited potential for mosquito transmission of genetically engineered, live-attenuated Venezuelan equine encephalitis virus vaccine candidates.

A single amino acid change in the E2 glycoprotein of Venezuelan equine encephalitis virus affects replication and dissemination in Aedes aegypti mosquitoes

Comparative neurovirulence of attenuated and non-attenuated strains of Venezuelan equine encephalitis virus in mice.

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