Individual and Bivalent Vaccines Based on Alphavirus Replicons Protect Guinea Pigs against Infection with Lassa and Ebola Viruses

Pushko, Peter; Geisbert, Joan B.; Parker, Michael D.; Jahrling, Peter B.; Smith, Jonathan

doi:10.1128/jvi.75.23.11677-11685.2001

Cited by 152 publications

(136 citation statements)

References 33 publications

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“…Alphavirus replicon particle vaccines have been successfully used to induce immune responses in small animals to a variety of exogenous viral proteins and usually induce antibody and T cell responses that protect from virus challenge (22,28,(38)(39)(40)(41)(42)(43). For instance, SINV replicon particle vaccines protect mice from mucosal challenge with vaccinia virus expressing HIV gag (38) and from herpes simplex virus infection (28).…”

Section: Discussionmentioning

confidence: 99%

Modulation of disease, T cell responses, and measles virus clearance in monkeys vaccinated with H-encoding alphavirus replicon particles

Pan

Valsamakis

Colella

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Section: Discussionmentioning

confidence: 99%

Modulation of disease, T cell responses, and measles virus clearance in monkeys vaccinated with H-encoding alphavirus replicon particles

Pan

Valsamakis

Colella

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…The guinea pigs that survived challenge were found to be viremic on day 7 after challenge. In a similar study, strain 13 guinea pigs inoculated with VEEV-replicons expressing GP produced about the same level of antibodies as the strain 2 guinea pigs but were completely protected from a guinea pig-adapted EBOV challenge [80,82]. No viremia was detected in these animals 7 days after challenge.…”

Section: Veev-vectored Ebola Hemorrhagic Fever and Marburg Virus Vaccmentioning

confidence: 64%

“…Pushko et al then used the VEE-replicons to evaluate the efficacy of replicons expressing the LSV GP (LGP) and the EBOV GP (EGP) in guinea pigs [82]. Guinea pigs were vaccinated with LNP, LGP, EGP (the EGP results were described in the above VEE-replicon-vectored EBOV vaccine section), a mixture of LNP+LGP or LGP + EGP, or with a double promoter replicon expressing both LGP and EGP (LGP/EGP).…”

Section: Veev-vectored Lassa Fever and Ebola Hemorrhagic Fever Vaccinesmentioning

confidence: 99%

Viral vectors for use in the development of biodefense vaccines

Lee

Hadjipanayis

Parker

2005

Advanced Drug Delivery Reviews

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“…Recently, a live vesicular-stomatitis virus vaccine expressing GP was demonstrated to protect mice from lethal EBOV infection [61]. Of the most well-studied vectored vaccine approaches for filoviruses are the Venezuelan equine encephalitis (VEE) replicon particle (VRP), in which the antigen of interest is individually inserted in place of VEE structural genes [59,60,[62][63][64][65]. VRP vaccines encoding GP have been the most successful of the six structural proteins tested, which also include NP, VP24, 30, 35 and 40 [10,52,62,63,65].…”

Section: Vaccine Approaches For Filovirusesmentioning

confidence: 99%

“…Of the most well-studied vectored vaccine approaches for filoviruses are the Venezuelan equine encephalitis (VEE) replicon particle (VRP), in which the antigen of interest is individually inserted in place of VEE structural genes [59,60,[62][63][64][65]. VRP vaccines encoding GP have been the most successful of the six structural proteins tested, which also include NP, VP24, 30, 35 and 40 [10,52,62,63,65]. The VRP vaccine encoding GP is sufficient to completely protect nonhuman primates against MARV, although these animals were only partially protected against EBOV when vaccinated with 10 7 plaque-forming units (pfu) [56,65].…”

mentioning

confidence: 99%

Filovirus-like particles as vaccines and discovery tools

Warfield

Swenson

Demmin

et al. 2005

Expert Review of Vaccines

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Ebola and Marburg viruses are members of the family Filoviridae, which cause severe hemorrhagic fevers in humans. Filovirus outbreaks have been sporadic, with mortality rates currently ranging from 30 to 90%. Unfortunately, there is no efficacious human therapy or vaccine available to treat disease caused by either Ebola or Marburg virus infection. Expression of the filovirus matrix protein, VP40, is sufficient to drive spontaneous production and release of virus-like particles (VLPs) that resemble the distinctively filamentous infectious virions. The addition of other filovirus proteins, including virion proteins (VP)24, 30 and 35 and glycoprotein, increases the efficiency of VLP production and results in particles containing multiple filovirus antigens. Vaccination with Ebola or Marburg VLPs containing glycoprotein and VP40 completely protects rodents from lethal challenge with the homologous virus. These candidate vaccines are currently being tested for immunogenicity and efficacy in nonhuman primates. Furthermore, the Ebola and Marburg VLPs are being used as a surrogate model to further understand the filovirus life cycle, with the goal of developing rationally designed vaccines and therapeutics. Thus, in addition to their use as a vaccine, VLPs are currently being used as tools to learn lessons about filovirus pathogenesis, immunology, replication and assembly requirements.Expert Rev. Vaccines 4(3), 429-440 (2005) Ebola (EBOV) and Marburg (MARV) viruses are the only members of the family Filoviridae, and were named according to their filamentous shape. EBOV and MARV cause acute and rapidly progressive hemorrhagic fever with mortality rates in humans of up to 90% [1,2]. The reservoir for filoviruses is unknown, although the consumption of monkey meat is often associated with onset of disease. Animals ranging from insects to mammals have been analyzed in the hopes of identifying a carrier, but to no avail [3]. After exposure, the onset of clinical symptoms can be as short as 2 days and as long as 21, although most infected humans and nonhuman primates die within 7-10 days of exposure [4]. In addition to hemorrhage and bleeding, other symptoms of filovirus infection include fever, headache, generalized myalgia, prostration, conjunctivitis, rash, lymphadenopathy, pharyngitis and edema [5].Filoviruses are considered serious public health threats, and are classified as biosafety level (BSL)-4 agents and Category A biothreat agents by the US Centers for Disease Control and Prevention [6,101]. Features that characterize filoviruses as a significant global health risk include high morbidity and mortality rates, potential for person-to-person transmission, relative stability in the environment, and feasibility of large-scale production. Additionally, the filoviruses have a low infectious dose, an extremely rapid rate of replication and can be easily transmitted, including via aerosols [4,7,8]. Bolstering the fear of their use as bioterrorism agents, several hemorrhagic fever viruses have a history of state-sponsor...

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Individual and Bivalent Vaccines Based on Alphavirus Replicons Protect Guinea Pigs against Infection with Lassa and Ebola Viruses

Cited by 152 publications

References 33 publications

Modulation of disease, T cell responses, and measles virus clearance in monkeys vaccinated with H-encoding alphavirus replicon particles

Modulation of disease, T cell responses, and measles virus clearance in monkeys vaccinated with H-encoding alphavirus replicon particles

Viral vectors for use in the development of biodefense vaccines

Filovirus-like particles as vaccines and discovery tools

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