Viral vectors for use in the development of biodefense vaccines

Lee, John S.; Hadjipanayis, Angela; Parker, Michael D.

doi:10.1016/j.addr.2005.01.011

Cited by 21 publications

(14 citation statements)

References 99 publications

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“…We have documented that, compared to wild-type LCMV, r3LCMV is attenuated in mice, suggesting that in vivo, r3Candid viruses would be, compared to Candid #1, further attenuated and therefore safer, but this r3Candid virus should retain levels of replication in vivo sufficient to induce a protective immune response. Preexisting immunity to the vector used to vaccinate can interfere with the ability of this vector to stimulate a protective immune response against the antigens expressed by the vector (16). In this regard, the highly restricted area where JUNV is endemic makes it highly unlikely that preexisting immunity to JUNV would interfere with the use of Candid #1 as a vaccine platform.…”

Section: Discussionmentioning

confidence: 99%

Rescue from Cloned cDNAs and In Vivo Characterization of Recombinant Pathogenic Romero and Live-Attenuated Candid #1 Strains of Junin Virus, the Causative Agent of Argentine Hemorrhagic Fever Disease

Emonet

Seregin

Yun

et al. 2011

J Virol

101

137

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The New World arenavirus Junin virus (JUNV) is the causative agent of Argentine hemorrhagic fever (AHF), which is associated with high morbidity and significant mortality. Several pathogenic strains of JUNV have been documented, and a highly attenuated vaccine strain (Candid #1) was generated and used to vaccinate the human population at risk. The identification and functional characterization of viral genetic determinants associated with AHF and Candid #1 attenuation would contribute to the elucidation of the mechanisms contributing to AHF and the development of better vaccines and therapeutics. To this end, we used reverse genetics to rescue the pathogenic Romero and the attenuated Candid #1 strains of JUNV from cloned cDNAs. Both recombinant Candid #1 (rCandid #1) and Romero (rRomero) had the same growth properties and phenotypic features in cultured cells and in vivo as their corresponding parental viruses. Infection with rRomero caused 100% lethality in guinea pigs, whereas rCandid #1 infection was asymptomatic and provided protection against a lethal challenge with Romero. Notably, Romero and Candid #1 trans-acting proteins, L and NP, required for virus RNA replication and gene expression were exchangeable in a minigenome rescue assay. These findings support the feasibility of studies aimed at determining the contribution of each viral gene to JUNV pathogenesis and attenuation. In addition, we rescued Candid #1 viruses with three segments that efficiently expressed foreign genes introduced into their genomes. This finding opens the way for the development of a safe multivalent arenavirus vaccine.Arenaviruses are enveloped viruses with a bisegmented negative-strand (NS) RNA genome. Each genomic RNA segment, L (ca. 7.3 kb) or S (ca. 3.5 kb), uses an ambisense coding strategy to direct the synthesis of two polypeptides in opposite orientations and separated by a noncoding intergenic region (IGR) that acts as a transcription termination signal for the virus polymerase (21, 29). The S RNA encodes the viral glycoprotein precursor (GPC) and the nucleoprotein (NP). The GPC is posttranslationally cleaved by the cellular site 1 protease to yield the two glycoproteins GP1 and GP2, which, embedded in the lipid bilayer, form the viral spikes in the mature virion that are crucial for receptor recognition and cell entry. The L RNA encodes the viral RNA-dependent RNA polymerase (or L polymerase) and the small (ca. 11-kDa) RING finger protein Z that is the arenavirus counterpart of the M protein found in many other NS RNA viruses (24,28,30).

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Section: Discussionmentioning

confidence: 99%

Rescue from Cloned cDNAs and In Vivo Characterization of Recombinant Pathogenic Romero and Live-Attenuated Candid #1 Strains of Junin Virus, the Causative Agent of Argentine Hemorrhagic Fever Disease

Emonet

Seregin

Yun

et al. 2011

J Virol

101

137

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“…Alphavirus-based vectors have been used to induce protective immunity against LASV in guinea pigs (Pushko et al, 2001), and more recently a recombinant VSV where LASV GP substituted for the VSV G was shown to provide protection against a lethal challenge with LASV (Geisbert et al, 2005). Likewise, the alphavirus Venezuelan equine encephalitis virus (Lee, Hadjipanayis, and Parker, 2005), and the 17D Yellow fever vaccine (Bredenbeek et al, 2006) have shown promising results. Whether these recombinant vaccines provide long–term protection remains to be determined, an issue highly relevant in the case of LF due to a cumulative lifetime risk of exposure to LF vaccine within the West Africa human population.…”

Section: Harnessing Arenavirus Reverse Genetics For the Development Omentioning

confidence: 99%

Arenavirus reverse genetics: New approaches for the investigation of arenavirus biology and development of antiviral strategies

2011

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Several arenaviruses, chiefly Lassa virus, cause hemorrhagic fever disease in humans and pose a significant public health problem in their endemic regions. On the other hand the prototypic arenavirus LCMV is a superb workhorse for the investigation of virus-host interactions and associated disease. The development of novel antiviral strategies to combat pathogenic arenaviruses would be facilitated by a detailed understanding of the arenavirus molecular and cell biology. To this end, the development of reverse genetics systems for several arenaviruses has provided investigators with novel and powerful approaches to dissect the functions of arenavirus proteins and their interactions with host factors required to complete each of the steps of the virus life cycle, as well as to cause disease.

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“…The rabies virus can be further attenuated through genetic mutations or be inactivated by treatment with β-Propiolactone [28,45]. SFV and VEE, both alphaviruses, share many vaccine qualities which were reviewed by Lee et al, Choi et al, and Lundstrom [42,43,46]. Alphaviruses can accept foreign genes of about 5 kb which replace the genes encoding the viral structural proteins resulting in replication deficient replicons [42,43].…”

Section: Venezuelan Equine Encephalitis Virus-based Vectorsmentioning

confidence: 99%

“…SFV and VEE, both alphaviruses, share many vaccine qualities which were reviewed by Lee et al, Choi et al, and Lundstrom [42,43,46]. Alphaviruses can accept foreign genes of about 5 kb which replace the genes encoding the viral structural proteins resulting in replication deficient replicons [42,43]. Production of the replicons requires a helper plasmid encoding the viral structural proteins co-transfected into host cells along with the desired viral genome.…”

Section: Venezuelan Equine Encephalitis Virus-based Vectorsmentioning

confidence: 99%