An influenza vaccine developed by scientists at Okairòs (Rome, Italy), and tested in animal models by scientists at the U.S. Food and Drug Administration (FDA) has potential as a “universal” vaccine to protect humans against a broad range of influenza viruses. The FDA scientists have been studying related universal influenza vaccines, and chose to study theOkairòs vaccine because it is based on a virus to which humans have no prior exposure, thus avoiding any issue about prior immunity.
Like a variety of other universal vaccine candidates, the vaccine triggered immune responses against conserved antigens—viral protein targets that mutate only slowly. These proteins are similar among many strains of influenza viruses, and therefore can generate immune responses that cross-react among virus strains.
The study results are important because successful development of a universal influenza vaccine could protect humans against a broad variety of related influenza viruses rather than just a few. Production and manufacture of a vaccine matched to a new influenza virus takes about six months. A universal vaccine, in contrast, could be used immediately “off-the-shelf,” and could provide some protection against a newly emerging influenza virus that experts had not identified during worldwide surveillance of these viruses, e.g., as occurred with the 2009 H1N1 pandemic virus (swine flu). A universal vaccine would decrease the severity of disease, speed up the ability of the body to clear itself of the virus, and reduce the fatality rate of infections until a specific vaccine against that virus is available.
The Okairòs scientists made their vaccine by genetically modifying a virus called PanAd3, which was isolated from a bonobo (a type of great ape). The modified virus, called a vector, carried two genes for proteins conserved among many different influenza viruses: M1 and NP. The vector can infect cells, causing them to express M1 and NP influenza antigens and thus immunize the recipient. However, it cannot replicate itself and spread.
To test the PanAd3 vaccine, the FDA scientists administered a single dose in the nose of mice. This single dose caused a strong immune response that protected the animals against infection a few weeks later by exposure to a high dose of a very virulent (disease-causing) influenza virus called A/FM. Specifically, the vaccine not only triggered antibody production, but also activated immune system cells called T cells. Importantly, strong T cell immunity was found in the lungs, the site of infection.
Some similar vaccine candidates are based on vectors made from a related human virus (Ad5), and work well in animals. However, because Ad5 is a human virus, many humans have already been exposed to it and have antibodies that can reduce its effectiveness as a vaccine. In contrast, because humans are generally not exposed to PanAd3, their immune systems are not primed to attack it; therefore, the immune system is much less likely to block the vaccine.
The FDA and Okairòs scientists concluded that the success of the PanAd3-based vector in protecting mice from a virulent influenza virus suggests that the vaccine is worth further study and development as a potential universal vaccine against a broad variety of influenza viruses that pose global threats to human health.
The FDA scientists are in the Center for Biologics Evaluation and Research, Office of Cellular, Tissue, and Gene Therapies.
“Vaccination to Conserved Influenza Antigens in Mice Using a Novel Simian Adenovirus Vector, PanAd3, Derived from the Bonobo Pan paniscus”
PLoS ONE (2013) 8(3): e55435. Doi:10.1371/journal.pone.0055435
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