Gene Therapy … Against Influenza?
Interesting proof of concept experiment. Just one squirt of antibody-expressing modified AAV up the nose and animals are protected against a wide range of influenza strains – and potentially many other diseases. But there’s a long way to go before this becomes a reality in human medicine.
Intranasal Antibody Gene Transfer in Mice and Ferrets Elicits Broad Protection Against Pandemic Influenza. Sci Transl Med Vol. 5, Issue 187, p. 187ra72 DOI: 10.1126/scitranslmed.3006299
The emergence of a new influenza pandemic remains a threat that could result in a substantial loss of life and economic disruption worldwide. Advances in human antibody isolation have led to the discovery of monoclonal antibodies (mAbs) that have broad neutralizing activity against various influenza strains, although their direct use for prophylaxis is impractical. To overcome this limitation, our approach is to deliver antibody via adeno-associated virus (AAV) vectors to the site of initial infection, which, for respiratory viruses such as influenza, is the nasopharyngeal mucosa. AAV vectors based on serotype 9 were engineered to express a modified version of the previously isolated broadly neutralizing mAb to influenza A, FI6. We demonstrate that intranasal delivery of AAV9.FI6 into mice afforded complete protection and log reductions in viral load to 100 LD50 (median lethal dose) of three clinical isolates of H5N1 and two clinical isolates of H1N1, all of which have been associated with historic human pandemics (including H1N1 1918). Similarly, complete protection was achieved in ferrets challenged with lethal doses of H5N1 and H1N1. This approach serves as a platform for the prevention of natural or deliberate respiratory diseases for which a protective antibody is available.
Pretty damn important. Continue reading
A new vaccine strategy could make flu shots cheaper, safer, and easier to produce. Using synthetic messenger RNA (mRNA) instead of proteins purified from viruses, German scientists have shown they can protect mice, ferrets, and pigs against influenza. Science Now: … Continue reading
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The segmented nature of the influenza virus genome complicates the process of genome packaging because at least one complete set of eight viral RNA segments has to be packaged into a virus particle to produce infectious progeny. The mechanism by … Continue reading
It was my priveledge to work with Brian Mahy many years ago. Brian has just retired as long-serving Editor of Virus Research, and his swansong is an excellent special issue on negative strand RNA viruses – an important read for … Continue reading
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Tagged Biology, Bornavirus, Hendra, Influenza, measles, Microbiology, Nipah, paramyxoviruses, rhabdovirus, RNA, Science, Virology, virus
Although it has not been in the news much recently, the highly pathogenic avian influenza A virus subtype H5N1 has been endemic in some bird species since its emergence in 1996 and its ecology, genetics and antigenic properties continue to … Continue reading
To deliver their genomes into host cells during entry, enveloped viruses contain glycoproteins that bind to cellular receptors and cause fusion of viral and cellular membranes. The influenza virus Hemagglutinin (HA) protein is the archetypal viral fusion glycoprotein, promoting entry … Continue reading
The influence that combinations of mutations have on an organism’s adaptive fitness is known as epistasis. Knowing that can help us make better flu vaccines. Continue reading
How risky is public transport? Continue reading