Wednesday, December 5, 2012

Flu shots may interfere with broad immunity developed after natural infection / Vaccine

From a public health standpoint, a true pandemic flu--a la 1918--is what might cause really large mortality and morbidity.  Seasonal flu causes a few hundred deaths in healthy people, and perhaps a few thousand in the frail elderly in the US each year.  (We don't have a good count of cases, and rely on modeling by CDC for the numbers of flu deaths in US adults.)  So immunity that extends to a large number of flu viruses, including potentially much more virulent viruses, is what is desired.  How do flu vaccinations measure up at providing broad protection to a variety of flu viruses?

This blog has discussed research by Danuta Skowronski and others, who used Canadian government health statistics (with consistent results from many provinces) to discover that getting flu shots in 2008 made people about twice as likely to come down with a "medically attended" case of swine flu in 2009-10.  Skowronski et al. then infected ferrets with influenza virus and found that the vaccinated ferrets came down with more severe disease, and had higher viral titres in the lungs, than ferrets who had not received 'appropriate' flu vaccine.  Here is a YouTube presentation which is a very clear and comprehensive discussion of what the data may mean.

Now Dutch researchers provide evidence in both human and animal models that the immunity generated by natural infection provides significant cross-immunity to related flu viruses, which is lacking from vaccination.  (However, other researchers have said that effective cross-immunity does occur from vaccination.)

When T cells from children with CF who are vaccinated yearly for flu were compared with T cells from healthy, unvaccinated children, the virus-specific CD8+ T cell response was better in the unvaccinated children than in children getting yearly flu shots.

These findings need to be replicated, but they may provide an explanation to support the epidemiological findings in Canada.

The findings also mean that research that measures flu vaccine efficacy by looking at antibody titres while ignoring cellular immunity, failing to check for crossover immunity and failing to look at whether vaccine recipients actually catch the flu and how ill they become, is of limited value.

Here is the abstract:
Annual influenza vaccination affects the development of heterosubtypic immunity
  • a Department of Virology, Erasmus MC, Rotterdam, The Netherlands
  • b Intensive Care and Department of Pediatric Surgery, Erasmus MC- Sophia Children's Hospital, Rotterdam, The Netherlands
  • c ViroClinics Biosciences, Rotterdam, The Netherlands

Annual vaccination of healthy children >6 months of age against seasonal influenza has been recommended by public health authorities of some countries. However, currently used seasonal vaccines provide only limited protection against (potentially) pandemic influenza viruses. Furthermore, we recently hypothesized that annual vaccination may hamper the development of cross-reactive immunity against influenza A viruses of novel subtypes, that would otherwise be induced by natural infection. Here we summarize our findings in animal models in which we demonstrated that vaccination against influenza A/H3N2 virus reduced the induction of heterosubtypic immunity against highly pathogenic avian influenza A/H5N1 virus, otherwise induced by a prior infection with influenza A/H3N2 virus. The reduction of heterosubtypic immunity correlated with reduced virus-specific CD8+ T cell responses. An additional study was performed in humans, in which we collected peripheral blood mononuclear cells from annually vaccinated children with cystic fibrosis (CF) and age-matched unvaccinated healthy control children to study the virus-specific T cell response. An age-related increase of the virus-specific CD8+ T cell response was observed in unvaccinated children that was absent in vaccinated children with CF. These findings highlight the importance of the development of vaccines that provide protection against influenza A viruses of all subtypes.

► Annual vaccination of all children against flu is recommended in some countries. ► In animal models, H3N2-vaccination prevents heterosubtypic immunity against H5N1. ► Reduction of this immunity correlated with the reduction of flu-specific CTLs. ► Unvaccinated children had more flu-specific CTLs than vaccinated children with CF. ► These findings highlight the importance of the development of universal flu vaccines.

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