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We used a propagation-defective, single-cycle, alphavirus replicon vector system to produce virus-like replicon particles (VRP) expressing the hemagglutinin (HA) and neuraminidase (NA) proteins from influenza A/Wyoming/03/2003 (H3N2). Efficient production methods were scaled to produce pilot lots of HA VRP and NA VRP and clinical lots of HA VRP. HA VRP-induced high-titered antibody responses in mice, rabbits and rhesus macaques, as measured by ELISA or hemagglutination inhibition (HI) assays, and robust cellular immune responses in mice and rhesus macaques, as measured by IFN-gamma ELISPOT. NA VRP also induced cellular immune responses in mice. A toxicology study with HA VRP and NA VRP in rabbits showed no adverse effects in any parameter. These studies support clinical testing of alphavirus replicon vaccines for influenza.
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http://dx.doi.org/10.1016/j.vaccine.2007.09.038 | DOI Listing |
Microb Biotechnol
September 2025
KU Leuven, Department of Biosystems, Laboratory of Gene Technology, Leuven, Belgium.
In this millennium, Marburgvirus (MARV) outbreaks with very high mortality but still small case numbers (< 400) were observed with increasing frequency in Africa. Ecologists identified Egyptian Rousettus bats (ERB) as viral reservoir species causing occasional zoonotic spillover events, mostly in humans intruding into their cave habitats as miners or tourists. So far only short human-to-human transmission chains have been documented.
View Article and Find Full Text PDFNucleic Acids Res
July 2025
Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, Stockholm SE-106 91, Sweden.
Small nucleolar RNAs (snoRNAs) are prevailing components of the chromatin-associated transcriptome. Here we show that specific snoRNAs are required for the activation of immune response genes and for survival during viral infections in Drosophila melanogaster. We have studied snoRNA:U3:9B, a chromatin-associated snoRNA that binds to a large number of protein coding genes, including immune response genes.
View Article and Find Full Text PDFVaccines (Basel)
June 2025
Research and Development Department, MSD Animal Health, 5831 AN Boxmeer, The Netherlands.
A number of different vaccines against feline leukemia virus (FeLV) are available; however, there is continuous debate regarding the efficacy advantages of adjuvanted vaccines versus the potential safety advantages of non-adjuvanted vaccines. For this reason, we developed a non-adjuvanted vaccine based on a replicon RNA particle (RP) expressing the FeLV gp85 envelope protein, which possesses the safety of a non-adjuvanted vaccine while consistently providing high efficacy. In two efficacy studies, a high-level of protection against virulent FeLV challenge was demonstrated with two doses given 3 weeks apart based on the prevention of FeLV p27 antigenemia.
View Article and Find Full Text PDFJ Biol Chem
August 2025
Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín-CONICET, Argentina. Electronic address:
mRNA technology has widely incorporated modified nucleotides to temper innate immune activation by foreign RNA and achieve high levels of heterologous protein expression. However, the incorporation of modified nucleotides has had limited application to self-amplifying (sa) RNAs, as it impeded heterologous protein expression. Here, we used a reporter replicon of the attenuated TC-83 strain of Venezuelan equine encephalitis virus (VEEV) to investigate the impact of modified nucleotide incorporation on the replication capacity of the saRNA in transfected cells.
View Article and Find Full Text PDFEmerg Microbes Infect
December 2025
Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Biscoumarin derivatives were evaluated for antiviral activity against chikungunya virus (CHIKV), a re-emerging mosquito-borne alphavirus with no approved treatment. Compounds 3 and 4 demonstrated potent antiviral efficacy, with EC₅₀ values of 2.85 ± 0.
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