New nasal spray vaccine completes phase 1 trials

INFLUENZA SPECIAL: New research has led to the development of a safely attenuated live influenza vaccine produced in cell culture and applied through a nasal spray, which could be available on the market by 2012.

Started in 2005 with a €9.2 million grant from EU, the FLUVACC project was set up to develop a new type of vaccine that could be produced faster and more effectively. Currently, injectable inactivated virus preparations dominate the influenza vaccine market, even though vaccines based on live attenuated viruses lead to longer-lasting immunity and are effective against emerging drift variants.
However, while the live attenuated viruses currently available do have a good safety record, unexpected complications in the young, elderly and immuno-compromised can arise due to shedding of the vaccine virus. The production of conventional influenza vaccine is also time intensive and hard to scale up, as it relies on the use of pathogen-free chicken eggs as mini vaccine factories.
Virologist Dr Thomas Muster, CEO of AVIR Green Hills Biotechnology, is leading the consortium behind FLUVACC, which has shifted vaccine production away from the traditional methods by developing replication-deficient live attenuated vaccines that are produced in cell culture.
Opting for intranasal delivery means that the administration of the vaccine is not only easier and less painful, but stimulates a protective immune reaction directly at the site of the virus entry, leading to higher efficacy.
Dr Muster stressed the importance of inducing immunogenicity and protection just at the site of entry of the virus. “You don’t get flu in the arm, you get it in the respiratory tract,” he told attendees at the EU briefing.
Instead of using egg-produced viral proteins, the new vaccine contains whole replication-deficient viruses that generate a strong immune response. It is based on the deletion of the pathogenicity factor NS1: it looks like an influenza virus to the body and induces an immune response, but is incapable of causing disease.
The team recently reached the milestone of the conclusion of phase 1 clinical trials, the results of which were published a few months ago in the Journal of Infectious Diseases (Wachek et al., J. Infect. Dis., 201:354-362). The study showed that vaccination with an influenza virus-strain lacking the viral interferon antagonist NS1 induces statistically significant levels of strain-specific and cross-neutralising antibodies.
No vaccine shedding
“It is very safe and superior to the conventional vaccine,” said Dr Muster. “We do not have shedding of the vaccine virus, which is important when you compare it with the current live attenuated vaccines, because there is no possibility of the transmission of the vaccine virus to an immuno-compromised person. This is quite a problem for our direct competitor on the market in the US, FluMist,” explained Dr Muster, in reference to a different type of intranasal vaccine already available in the US. The new vaccine also induces cross-reactive neutralising antibodies against drift variants, which again is very important as conventional vaccines are usually only active against the strain from which they are made.
By using a reverse genetics method, the group is also able to generate new strains within a week or two, compared with the three months it takes by conventional methods.
Of course, there is a risk with any live attenuated vaccines that the vaccine virus might recombine with the wild virus, which is why their use is restricted until a pandemic has been declared.
Dr Muster said his group’s vaccine is a little different. “The risk of reassortment is a thousand times lower than with a conventional live attenuated vaccine, because it just goes in your nose and doesn’t come out anywhere. But still, we have to stick with the best risk management policy of not starting administration before a pandemic.”
The virologist hopes that the consortium will have finished phase two trials by the end of the year, and will enter into phase three trials involving some 4,500 people next year, before the flu season of 2011.