Universal Weapon against Influenza

11. November 2008

Influenza viruses have the annoying quality to permanently change. Since the human immune system only remembers the last virus type, risk groups have to go for flu shots practically every year. The solution: A universal weapon. Researchers are currently working on it. But is there land in sight?

At the Oxford University, a universal flu vaccine was developed which is to be clinically tested on persons for the first time now. This wonder weapon is supposed to protect against all flu viruses type A namely against all subvariations of H1, H2, H3, H4, H5, etc. as Dr. Sarah Gilbert of the Jenner Institute explains to DocCheck. The A pathogen is considered responsible for example for pandemics. The hope of the researchers in Oxford: If the phase I study is positive, the way might be paved for a potent protection against all seasonal influenza and the bird flu. Those problems always occurring when a new vaccine has to be manufactured at short notice and in sufficient quantities might be a thing of the past. We all might recall the hysterics regarding the H5N1 respectively the bird flu pathogen. The fear went around that people might catch the virus and that the H5N1 virus might mutate enough to cause a pandemic. Horror scenarios went about that the development of the vaccine might progress too slow causing worldwide shortages. The feared pandemic did not come but the risk did not vanish either.

From antibodies to killer cells

The Oxford scientists are not the only ones targeting their research on a ‘universal flu jab’. At Acambis – a Sanofi subsidiary by now – Belgian researchers are working on a new vaccine against all A pathogens as well. According to a report last February, clinical tests on persons provided promising results. Obviously the Belgians are a little bit ahead. But here as well, the scientists assume that it will take another couple of years to test the full range of the viruses. But what is the difference in approaches between the Oxford scientists and the Belgians? Gilbert explains to DocCheck: “They are using a different flu protein (M2e) and are raising antibodies against it. We are using NP and M1 and are boosting cellular immune responses. Killer immune cells can then kill flu-infected cells.”

Defiant proteins in and on the flu virus

Conventional vaccines create antibodies which are used as weapons against surface proteins hemagglutinin (H) and neuramindase (N) of the flu virus. But these proteins change in the course of time and with the pathogen which leads to it that a vaccine only protects against a particular pathogen. Thus the researchers in the UK and also those in Belgium are looking for virus proteins staying relatively stable affronting the ever changing pathogens. Gilbert’s team developed a vaccine targeting on proteins such as for example M1 in the flu virus. They meet those requirements exactly – meaning that they hardly change over a longer period of time and are also less delicate regarding changing pathogens.

Still many tests until it is ready for the market

One of the modules with those requirements the Belgian researchers used as well. They decided to use the protein M2, though. Contrary to the English approach it is a matter of a surface protein of the flu virus. Initial clinical tests in Belgium with “Acam-Flu-A” showed that nine out of ten test persons developed antibodies against the flu virus. This took place early this year. Up to now, no more press releases concerning further tests or their results were published. And nothing about a stop of the project either. DocCheck asked Gilbert which achievements she expects for her own tests of the “universal flu vaccine”: “We have just started a phase I trial and are seeing good safety and immunogenicity results. Next we will plan a challenge study where we vaccinate half the volunteers and expose them all to ‘flu virus’ to see if the vaccine can protect against infection. That study is expected to take place in the first half of next year.” And how long might it take until it will be available for all patients? “Difficult to say since we are an academic group at the beginning of clinical trials. But possibly 5 years.”

A complete protection is debatable

DocCheck inquired at the Institute for Virology at the Cologne University whether the approach of the two research groups could be an effective instrument against influenza viruses of all kinds. Dr. rer. nat. Rolf Kaiser stated: “This strongly depends on what the target is. The current strategy of vaccinating against influenza presents a very high protection. The disadvantage surly is that patients have to get their flu shots every year. In addition there is always the risk that another influenza strain than expected might spread thus resulting in not the ideal vaccination. The vaccines introduced by the two groups are supposed to achieve a protection by immunization against a component of the virus which is very similar in all influenza viruses but is not located on the surface of the virus but inside. The virus reproduction can be impaired, but a complete protection from infection with the flu is disputable. Should the virus reproduction be arrested – the infectiosity would be less as well as the danger of complications. But this is subject to speculations needing proof in future studies.”

Studies yet to prove the viability of universal flu vaccines

Dr. Thorsten Wolff, head of the “Pathogenicity mechanisms of influenza viruses” department at the Robert Koch-Institute confirms to DocCheck, that researchers are active in trying to trick the quick-change artists ‘flu virus’ in Germany as well. “If this new concept proves to be successful, it could be enough to get a flu shot just every couple of years. Despite some initial encouraging results in preclinical studies, the researchers will need several years to find out whether they can tame the flu with those new approaches. Current and future studies have to prove yet whether the hope for a universal flu vaccine can turn into reality”.

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