Science - September 10, 2009

Pigs to get jab against human flu

The Central Veterinary Institute (CVI) in Lelystad is testing its own vaccine to protect pigs against the Mexican flu. Without it the epidemic could spread to the pig population. Researcher Guus Koch believes there is every reason for more research on influenza in pigs.

A pig seeks attention from CVI researcher Guus Koch
 The Animal Science Group (ASG) of Wageningen UR in Lelystad will test a swine flu vaccine it has developed itself this month. The vaccine should protect the pig population if the virus jumps from humans to pigs. At the same time, investigations will be carried out into two commercially available influenza vaccines for pigs to see if they are effective against the new human influenza virus.
Preparations have been taking place in the past months for these experiments, which will be carried out on twenty to forty influenza-free pigs. This will take place in the high containment facility at the CVI in Lelystad. The laboratory is hermetically sealed, so no viruses or bacteria can get out.
The human influenza virus, officially known as the Novel Influenza A (H1N1) virus, surfaced for the first time in April in Mexico. Since then, it has spread explosively to the rest of the world. There has been much ado about the right name for the virus and the illness it causes. Early indications were that it was a swine flu because it was thought to have developed in a (Mexican) pig pen.
Influenza virologist Dr. Guus Koch of the CVI finds the term 'swine flu' misleading. 'So far this new 2009 H1N1 virus has only been detected in humans, but neither in pigs, nor in Mexico. Only one case has been reported - in Canada - where the 2009 virus was found in pigs. It was thought that an animal caretaker could have contracted the influenza virus after his visit to Mexico. The pigs fell sick; the caretaker too, even though the virus could not be traced in him. And yet, he must have been the carrier.'
It appears from the genetic composition of the Mexican virus that it is built up of influenza viruses circulating in pig pens worldwide. Three of the eight genes in the 2009 A (H1N1) virus could have come from the Spanish flu virus responsible for the 1918 pandemic which killed tens of millions of people worldwide within a year. In the same year, the virus had 'jumped' to pigs, further evolving genetically among the pig population, independently of its evolution in humans. In fact, one of the three 'Spanish' genes - responsible for the formation of surface proteins - plays an important role in human resistance against the virus.
Two of the eight genes are from a virus strain which has been making its rounds among the European pig population since 1979. This emerged from a gene hunt by a group of international virologists from the Erasmus University Medical Centre in Rotterdam and other institutions. These results were published at the end of May in Science.
Genetic blending
Somewhere along the line, the European strains must have blended with the strains prevalent in the North American pig population. Genetic blending can occur when body cells - especially those in the respiratory tracts - are simultaneously infected by different virus strains. That this blending must have occurred in pigs seems to be a logical deduction. Did this happen in a Mexican pig pen?
'This is no more than a conjecture for the time being', says Koch. 'It's baffling how and where the genetic blending could have taken place because hardly any pigs and therefore no virus strains have been transported between Europe and North America.'
Like humans, pigs can be infected by the so-called influenza type A viruses. There are 144 different virus types, with evolutionary origins in water birds.  Three of these viruses have been detected in pigs: virus strains of the H1N1, H1N2 and H3N2 types, according to a European research in which the CVI is involved.  These same virus types are also present among humans. Strains of these types alter their genetic morphologies constantly to get around the immune system of the host. In this way, they could succeed in outsmarting a vaccination campaign.
'The European research also reveals that almost every pig could have been infected with one of these virus strains at one time or another', says Koch. 'Influenza viruses are endemic; they are present in the pig population but hardly stand out. The virus then disappears generally by itself. Swine influenza is not a disease which leads to high mortalities among pigs, and reporting it is not mandatory. Pigs in Europe are hardly ever vaccinated against it because there are usually very few clinical symptoms, such as acute inflammation of the respiratory tract. Only when serious respiratory problems occur does a pig farmer undertake preventive vaccination measures.'
The global outbreak of the novel influenza virus has not yet prompted more research on pigs', laments Koch, who thinks there is every reason why it should do so. In the past, pig influenza viruses have regularly made the jump to humans. The transfer doesn't usually go smoothly, but it does happen, Koch warns. 'Up to now they were just incidents which have never led to a massive spread among humans. Now there are signs that this can take place with this new virus.'
Even though the novel H1N1 Mexican virus has not been detected in pigs yet, chances of a crossover are big. Recent research shows that the Mexican virus is very contagious. Together with the Utrecht University, the ASG have therefore developed a swine vaccine based on a surface protein of the new virus. This would enable pigs to develop immunity, which would reduce their susceptibility to the virus and decrease virus replication. Vaccination would therefore curtail its spread within the pig population.
There are plans to vaccinate nine pigs with this new vaccine in September. Subsequent blood tests will show if specific antibodies are produced. The pigs will then be deliberately infected with the 2009 influenza virus to study the workings in detail. In addition, two other groups of pigs will receive two existing influenza vaccines - developed for H1N1 virus strains in Europe and for H1N1 virus strains in North America - to see if they can protect pigs against the Mexican virus. 'The big differences make us think that they will not work', adds Koch.
Explosive rise in number of flu cases
The Mexican virus has already had the world in its grip for more than five months. It was detected for the first time in April in children in the United States, who had come from Mexico where the virus is suspected to have been around since the end of 2008. Worldwide, hundreds of thousands of people have been infected by the novel virus, and several thousands of these have died as a result. In contrast to the U.S. and European countries such as England and Spain, the Netherlands has not been affected much by the Mexican virus. So far, about two thousand Dutch people have been infected. This is just an estimate; since mid August, not every suspected case of infection has been monitored by analysing  saliva samples from the throat. The head count has also stopped.
Two Dutch people have died from the virus. Both were suffering from another, more serious ailment. In most of the cases, the disease symptoms resemble those of the common strains of winter flu. Young people seem to be more prone to infection than older people.
In the coming months, an explosive increase in the number of infections is expected because when the summer is over, 'normal life' starts up again. Schools are the ideal breeding ground for the influenza virus. In addition, temperatures drop, and the virus survives better in cold than in warm conditions. /Broer Scholtens