The hundreds of thousands of people affected by the 2009 pandemic may harbour some immunity to bird flu, say scientists this week. The claims follow research published in Vaccine, which shows that pigs infected with a flu virus closely related to the pandemic ‘swine flu’ strain developed immunity to bird flu.

 

“We would expect to see the same results in humans,” Kristien Van Reeth, lead author of the study, tells EHTF News.

 

The researchers infected 25 pigs with the H5N1 bird flu virus in the lab, 12 of which had been infected with a swine H1N1 virus four weeks earlier. They found that H1N1 gave the pigs immunity to bird flu, as none showed symptoms of the infection. All the animals infected only with H5N1 showed symptoms of bird flu.

 

“There was also a very strong protection against the replication of the virus in the respiratory tract,” says Van Reeth. The virus was isolated from respiratory tract tissue in three of the 10 animals tested that were infected with both viruses. By comparison, H5N1 was isolated from all of the other pigs tested. These immune responses could last up to two years in the pigs, she adds.

 

 

Andrew Pekosz, from the Johns Hopkins Bloomberg School of Public Health in Maryland, believes there is a “good possibility” that something similar would be seen in humans. “Data from this paper suggest that you will have some immunity to H5N1 after exposure to H1N1.”

 

The exact level of protection against bird flu is not known, explains Pekosz. But the parts of the immune system thought to be involved in the response documented by the authors are clearly associated with controlling infection and warding off severe disease. This could mean that people who have caught pandemic swine flu would still fall ill if they ever catch bird flu, but their immune system could prevent their illness from turning serious, he speculates.

 

Neither scientist can say for sure how long this protection could last, and note that this type of immunity fades over time. But both agree that an encounter with H1N1 is likely to leave people with a residual, protective response to the bird flu virus. It is unlikely to provide people with long-term protection against a pandemic of H5N1, nor will the number of cases of bird flu drop in countries currently affected by this virus, adds Peskosz.

 

Although the study published this week is based on experiments in pigs, Van Reeth has confidence that the results will hold true for humans. “The pig model of influenza is very reliable, it’s the best we have.”

 

 

Van Reeth and colleagues suggest that the pigs’ immune response to bird flu arose because the earlier H1N1 infection had stimulated both branches of their immune system to react against similar viruses.

 

A “cell-mediated immune response” specifically targets viruses within the influenza A family, to which swine flu and bird flu both belong. The other branch of the response involves the production of antibodies against a protein of the influenza virus called the neuraminidase. The neuraminidase molecule found in the swine flu and bird flu viruses belong to the same influenza A ‘N1’ subfamily.

 

By activating both branches of the immune system, these responses can protect against any invading flu viruses that share similar properties. By contrast, the immune protection generated after a flu jab targets a different protein, the haemagglutinin, and will only protect people from the flu virus that the vaccine is designed to target and a restricted range of closely related viruses.

 

Exactly how the cell-mediated and neuraminidase antibody responses work is unclear, but there is a growing body of evidence to suggest these cross-protective responses exist. Understanding more about them could help scientists design flu vaccines that respond to more than one strain of flu virus, says Pekosz.

 

 

The downside to these immune responses is that they fade over time. Van Reeth’s team infected the pigs with the bird flu virus four weeks after they had been infected with swine flu. The short period between infections could mean that the immune system was primed to work more effectively than it would do if the infections occurred further apart.

 

“It is likely that if we repeated the experiment with a larger time gap it would result in less protection,” explains Van Reeth. Longer experiments looking at the immune responses to two different viruses in mice have suggested this cross-protection disappears if exposure to the viruses is between two and three months apart.

 

But some evidence suggests that flu immunity can endure over time in humans, she says. People who became infected by the 1918 pandemic strain of H1N1 still harbour some immune response to the virus today. Those affected by the 1918 pandemic were probably also protected from other related strains of flu for several years, says Pekosz. “But by 1920 circulating H1N1 would have changed so much that it was able to start infecting people again, as the immune protection could not recognise the newer versions of the virus.”

 

 

According to one theory, exposure to a new flu virus boosts the immune response to the first strain of influenza a person ever came across. Reponses to other viruses that have affected them during their lifetime are also bolstered, but to a lesser extent.

 

The 2009 pandemic will only strengthen human defences against other flu viruses, says Van Reeth. “The more diverse flu viruses people come across, the better immune protection they will have.”

 

Prior infection with pandemic flu could also help protect people from illness caused by other seasonal strains during the winter flu season, points out Pekosz. Over the coming months it will become clear whether exposure to the early wave of swine flu has given a boost to the ability to fight off infection with strains of seasonal flu.

 

Every year, several different strains of seasonal flu circulate to cause illness in thousands of people. A seasonal strain of H1N1 has been part of this viral mix for years. Although the strain is distinctly different from the new pandemic virus, cross-protective immunity to infection with this more familiar strain could also give some immunity to bird flu, says Van Reeth. But this would not be as strong as the response that follows exposure to the pandemic virus, which is more closely related to H5N1.

 

Laboratory tests on blood samples from people exposed to seasonal H1N1 flu have confirmed that their antibodies also take aim at the bird flu virus.

 

 

Swine flu has stolen the limelight from bird flu since it was first spotted in April, but some still see the H5N1 virus as a significant threat to human health. Bird flu has killed around 60% of more than 440 people who got infected by the virus over the past six years, mostly in Asia and the Middle East. But Van Reeth does not believe the bird flu virus will gain the ability to spread easily between people and spark a pandemic, as swine flu has done.

 

In the six months since the H1N1 pandemic virus first appeared, EHTF has reported 15 confirmed cases of bird flu — down from the 31 confirmed cases reported during the first four months of the year. These fluctuations could be down to the cyclic nature of bird flu in the tropics, or a lack of reporting now that the H1N1 pandemic has arrived, says Pekosz.

 

The strain of swine flu used in the pig experiments is very closely related to the 2009 pandemic strain. In fact, the experimental virus is a “predecessor” of the new virus, notes Van Reeth. But the bird flu strain used in the experiments is not well adapted to infecting pigs and does not replicate in the respiratory tract to the same extent that swine flu viruses do. If the research was repeated with a better adapted H5N1 virus, as would be expected in a bird flu pandemic, the immune response will probably be weaker, she explains.