H1N1 lessons inform future pandemic response

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Dr. Danuta Skowronski and Dr. Naveed Janjua, co-investigators in an MSFHR-funded study looking at the risks posed by H3N2v, a new swine-origin influenza virus

An MSFHR-funded research team led by Dr. Danuta Skowronski, an epidemiologist at the BC Centre for Disease Control, is building on what it learned during the 2009 H1N1 pandemic to understand the risks posed by a new swine-origin influenza virus that could also pose a pandemic threat. The World Health Organization has labeled this variant, an H3N2 subtype, as “H3N2v.”

“To date, there have been 13 reported human cases of H3N2v, all in the US, mostly in children, half with no swine exposure, and with more undetected cases likely to have occurred.” said Skowronski. “The more we know about which populations are most vulnerable, the better we can gauge the risk of further spread and prepare our public health response.”

As part of its work on the H1N1 pandemic, the team discovered some key findings that informed their approach to H3N2v. By testing the blood of approximately 1,000 people, divided into 10-year age bands (e.g. 0-10 yrs old, 10-20 yrs old, etc.), they discovered that different age groups had different levels of immunity to H1N1 even before the pandemic. Nearly all children and young adults were susceptible to the pandemic H1N1 virus whereas those 80 years and older showed very high antibody protection even before the pandemic struck.

Taking a historical look at pandemic influenza to determine why the elderly had higher immunity, the researchers discovered that the strain of pandemic influenza that circulated between 1918 and 1930 was very similar to the 2009 pandemic H1N1 virus. The elderly had antibodies to this influenza virus as they encountered it in childhood and these antibodies recognized the closely-related 2009 pandemic strain. This underscored that antibodies to the first influenza virus we are exposed to in childhood are the most robust and powerfully recalled with boosting from other influenza exposures across the lifespan. This has huge implications for understanding and anticipating how other pandemic strains may impact a population.

Armed with this knowledge, the researchers looked at the characteristics of H3N2v. Taking a similar approach by examining blood samples from the same age groups they found that, unlike the pandemic H1N1 virus, young people are not fully susceptible to H3N2v. In fact, 25 percent of the population overall has some immunity to it. Upon closer examination, the researchers found that immunity levels varied by age group. Immunity levels were very low for those under the age of 14 and over the age of 40. However, approximately 50 percent of those aged 14 to 40 years had immunity.

Looking at historical patterns of influenza, the team has again correlated these patterns of immunity with the prior circulation of closely-related strains. Teens and young adults were likely “primed” by early childhood exposure to viruses from the mid-1990s that are most similar to H3N2v. Other H3N2 viruses have also circulated in people but only since 1968, which may explain why protection drops off significantly in those older than 40 years of age — an interesting hypothesis that requires more in-depth evaluation.

This research had immediate but also far-reaching implications. In the short term, BC health officials were able to make informed policy decisions about which populations to target with the 2009 and 2010 H1N1 immunization campaigns. This knowledge will also inform planning for future outbreaks. In the long term, these results also inform the science of influenza immunity showing how our early childhood experiences can affect our protection against subsequent pandemic threats later in life.

Skowronski emphasizes that this kind of rapid response research in support of public health risk assessment was possible only through multi-disciplinary collaboration, drawing on epidemiologic, virologic, immunologic, genomic, mathematical modeling and public health expertise among partner agencies within BC and across Canada.

“I’m very grateful for MSFHR’s support of this project — they were very responsive and flexible when we asked to repurpose our research grant to study this emerging influenza strain.”

Project partners
BC Centre for Disease Control, Vancouver, BC
BC Biomedical Laboratories Ltd, Surrey, BC
Vancouver Coastal Health Research Institute, Vancouver, BC
Centre Hospitalier Universitaire de Québec, Québec
Institut National de Santé Publique du Québec, Québec
Vaccine Evaluation Centre, Child & Family Research Institute, Vancouver, BC
National Microbiology Laboratory, Winnipeg, Manitoba
Public Health Agency of Canada-­CIHR Influenza Research Network