Objectives: Current Influenza vaccines elicit antibody mediated prophylactic immunity targeted to viral capsid antigens. Despite their global use these vaccines must be administered yearly to the population, cannot be manufactured until the circulating viral strain(s) have been identified and have limited efficacy. A need remains for Influenza vaccines addressing these issues and here we report the results of a Phase Ib trial of a novel synthetic Influenza vaccine (FLU-v) targeting T cell responses to NP, M1 and M2.
Methods: Forty-eight healthy males aged 18-40 were recruited for this single-centre, randomised, double blind study. Volunteers received one single low (250 μg) or high (500 μg) dose of FLU-v, either alone or adjuvanted. Safety, tolerability and basic immunogenicity (IgG and IFN-γ responses) parameters were assessed pre-vaccination and for 21 days post-vaccination.
Results: FLU-v was found to be safe and well tolerated with no vaccine associated severe adverse events. Dose-dependent IFN-γ responses >2-fold the pre-vaccination level were detected in 80% and 100% of volunteers receiving, respectively, the low and high dose adjuvanted FLU-v formulations. No formulation tested induced any significant FLU-v antibody response.
Conclusion: FLU-v is safe and induces a vaccine-specific cellular immunity. Cellular immune responses are historically known to control and mitigate infection and illness during natural infection.
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http://dx.doi.org/10.1016/j.vaccine.2012.04.089 | DOI Listing |
Chemistry
January 2025
Griffith University - Gold Coast Campus, Institute for Biomedicine and Glycomics, Parklands Drive, 4222, Southport, AUSTRALIA.
3-Fluoroneuraminosyl fluorides are invaluable probes for studying the catalytic mechanism of sialidases (neuraminidases), and as sialidase inhibitors. Significantly, when a C-3 equatorial fluorine is installed on a C-4 functionalised N-acylneuraminic acid (Neu)-based template, the compounds are potent and selective inhibitors of both influenza and parainfluenza sialidases, and of virus replication. Typically, the reported syntheses of 3-fluoroneuraminosyl fluorides involve either an enzymatic or a chemical synthesis that have uncontrolled stereoselectivity in the introduction of fluorine at C-3 of Neu and consequently yield a mixture of C-3 ax and C-3 eq fluoro derivatives.
View Article and Find Full Text PDFNat Microbiol
January 2025
State key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Generating effective live vaccines from intact viruses remains challenging owing to considerations of safety and immunogenicity. Approaches that can be applied in a systematic manner are needed. Here we created a library of live attenuated influenza vaccines by using diverse cellular E3 ubiquitin ligases to generate proteolysis-targeting (PROTAR) influenza A viruses.
View Article and Find Full Text PDFNat Chem Biol
January 2025
State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Manipulating viral protein stability using the cellular ubiquitin-proteasome system (UPS) represents a promising approach for developing live-attenuated vaccines. The first-generation proteolysis-targeting (PROTAR) vaccine had limitations, as it incorporates proteasome-targeting degrons (PTDs) at only the terminal ends of viral proteins, potentially restricting its broad application. Here we developed the next-generation PROTAR vaccine approach, referred to as PROTAR 2.
View Article and Find Full Text PDFBreath biopsy is emerging as a rapid and non-invasive diagnostic tool that links exhaled chemical signatures with specific medical conditions. Despite its potential, clinical translation remains limited by the challenge of reliably detecting endogenous, disease-specific biomarkers in breath. Synthetic biomarkers represent an emerging paradigm for precision diagnostics such that they amplify activity-based biochemical signals associated with disease fingerprints.
View Article and Find Full Text PDFArch Virol
January 2025
Department Experimental and Clinical Medicine, University of Florence, Florence, Italy.
The I38T substitution in the influenza virus polymerase-acidic (PA) subunit is a resistance marker of concern for treatment with the antiviral baloxavir marboxil (BXM). Thus, monitoring PA/I38T mutations is of clinical importance. Here, we developed three rapid and sensitive assays for the detection and monitoring of the PA/I38T mutation.
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