Persistent gag-specific T cell immunity would be a useful component of an effective HIV vaccine. The Flavivirus Kunjin replicon was previously engineered to persistently express HIV gag and was shown to induce protective responses in mice. We evaluated Kunjin replicon virus-like-particles expressing SIVgag-pol in pigtail macaques. Kunjin-specific antibodies were induced, but no SIV-specific T cell immunity were detected. Following SIVmac251 challenge, there was no difference in SIV viremia or retention of CD4 T cells between Kunjin-SIVgag-pol vaccine immunized animals and controls. An amnestic SIV gag-specific CD8 T cell response associated with control of viremia was observed in 1 of 6 immunized animals. Refinements of this vector system and optimization of the immunization doses, routes, and schedules are required prior to clinical trials.
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http://dx.doi.org/10.1016/j.virol.2008.01.006 | DOI Listing |
Pathogens
February 2022
School of Medical Science, Inflammatory Response and Infection Susceptibility Centre (iRiSC), Örebro University, 703 62 Örebro, Sweden.
Removal of genes coding for major parts of capsid (C), premembrane (prM), and envelope (E) proteins on the flavivirus genome aborts the production of infectious virus particles where the remaining genome forms a replicon that retains replicability in host cells. The C-prM-E proteins can also be expressed in with the flavivirus replicons to generate single-round infectious replicon virus-like particles (RVPs). In this study, we characterized the use of RVPs based on the Kunjin strain of WNV (WNV) as a putative WNV vaccine candidate.
View Article and Find Full Text PDFViruses
June 2021
Inflammatory Response and Infection Susceptibility Centre (iRiSC), School of Medical Science, Örebro University, 703 62 Örebro, Sweden.
The endoplasmic reticulum (ER) of eukaryotic cells is a dynamic organelle, which undergoes continuous remodeling. At the three-way tubular junctions of the ER, the lunapark (LNP) protein acts as a membrane remodeling factor to stabilize these highly curved membrane junctions. In addition, during flavivirus infection, the ER membrane is invaginated to form vesicles (Ve) for virus replication.
View Article and Find Full Text PDFMicroorganisms
November 2020
School of Medical Science, Inflammatory Response and Infection Susceptibility Centre (iRiSC), Örebro University, 703 62 Örebro, Sweden.
Kunjin virus (KUNV) is an attenuated strain of the severe neurotropic West Nile virus (WNV). The virus has a single-strand positive-sense RNA genome that encodes a polyprotein. Following gene expression, the polyprotein is cleaved into structural proteins for viral packaging and nonstructural proteins for viral replication and expression.
View Article and Find Full Text PDFAntimicrob Agents Chemother
July 2020
Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide, Australia.
Flaviviruses such as Zika virus (ZIKV), dengue virus (DENV), and West Nile virus (WNV) are major global pathogens for which safe and effective antiviral therapies are not currently available. To identify antiviral small molecules with well-characterized safety and bioavailability profiles, we screened a library of 2,907 approved drugs and pharmacologically active compounds for inhibitors of ZIKV infection using a high-throughput cell-based immunofluorescence assay. Interestingly, estrogen receptor modulators raloxifene hydrochloride and quinestrol were among 15 compounds that significantly inhibited ZIKV infection in repeat screens.
View Article and Find Full Text PDFViruses
November 2017
Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
West Nile virus (WNV) is a neurotropic flavivirus that can cause encephalitis in mammalian and avian hosts. In America, the virulent WNV strain (NY99) is causing yearly outbreaks of encephalitis in humans and horses, while in Australia the less virulent Kunjin strain of WNV strain has not been associated with significant disease outbreaks until a recent 2011 large outbreak in horses (but not in humans) caused by NSW2011 strain. Using chimeric viruses between NY99 and NSW2011 strains we previously identified a role for the non-structural proteins of NY99 strain and especially the NS3 protein, in enhanced virus replication in type I interferon response-competent cells and increased virulence in mice.
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