New Nasal Spray Influenza Vaccine May Enable Rapid Pandemic Response

Patricia Lobo

Safe and effective new nasal spray-delivered influenza vaccine could be produced quickly in high quantities during a pandemic infection.

During his presentation Monday at the World Vaccine Congress Lyon 2010, Thomas Muster, CEO and CSO, AVIR Green Hills Biotechnology, discussed deltaFLU, a new vaccine against influenza to be taken by nasal spray.

Currently, injectable inactivated virus preparations dominate the influenza vaccine market, even though vaccines based on live attenuated viruses lead to longer-lasting immunity, which is also effective against emerging drift variants. However, while the live attenuated viruses on the market have a good safety record, unexpected complications in young children, the elderly, and immuno-compromised people can arise from wide-spread use due to shedding of the vaccine virus.

Muster noted that industrial production of conventional influenza vaccine is time-intensive and hard to scale up, as it relies on the use of pathogen-free chicken eggs as mini-vaccine factories. Pathogen-free eggs are often in short supply and the technique can only be automated to a limited extent. Therefore, during an influenza pandemic, it would be difficult for supply to meet demand. Another drawback of vaccines produced in this way is that they cannot be given to people with an egg allergy.

With deltaFLU, AVIR Green Hills has developed a safely attenuated live influenza vaccine that is produced in cell culture and applied through a nasal spray device. Instead of using egg-produced viral proteins, this vaccine contains whole replication-deficient viruses that generate a strong immune response. Muster said it is based on the deletion of the pathogenicity factor NS1 so that it looks like an influenza virus to the body and induces an immune response, but is unable to cause disease. Clinical trials in human volunteers demonstrated that the vaccine is safe and immunogenic. Importantly, the vaccine induced a neutralizing response against not only homologous but also heterologous drift variants.

Characteristics of deltaFLU:

Nasal spray

The vaccine is applied by intranasal route with a spray device. This way of administration is easier and less painful than injection into a muscle and stimulates a protective immune reaction directly at the site of the virus entry leading to higher efficacy.

Safety

Muster stated that all experiments performed so far suggest that this vaccine is safe. The vaccine is replication-defective and no viral shedding upon immunization occurs. This suggests that even in the case of wide-spread use, unexpected complications in young children, the elderly and immune-compromised people are unlikely.

Immunity

The vaccine can induce an effective and long-lasting immune response against a wide range of influenza virus variants, which is only conditionally possible with conventional vaccines. This cross-protective immunity provides protection against even distantly related variants of pandemic influenza strains. The method of reverse genetics optimised in this project permits generation of an attenuated vaccine against any potential influenza virus, even highly virulent avian influenza variants, within a short period of time.

Production

The vaccine is produced in mammalian cells in tissue culture. This is efficient, fast and does not rely on the supply of eggs as used in traditional methods. The advantage of manufacturing vaccines in cultured cells is that production can be easily scaled up in case of increased demand by using bioreactors. Therefore, production in cell culture and the use of the optimised reverse genetics method means that a safe vaccine against any potential influenza virus could be generated quickly and in high quantities and thus fulfil logistic needs during a pandemic infection.