In March 2013, the first human contracted case of the new avian influenza (bird flu) virus, H7N9 was reported in China. There have been more than 350 confirmed human cases to date, resulting in more than 100 deaths. An interdisciplinary team of scientists from York University and the Public Health Ontario Laboratories conducted a large-scale whole proteome-wide immunoinformatics analysis to predict the susceptibility of different ethnic populations against the H7N9 virus. The study outcome identified the likely presence of cross-reactive T cell immunity in humans against the H7N9 virus; however, this cross-reactive immunity varies considerably across different ethnic populations. It was found that indigenous populations from various regions (including Canada) may be at an elevated risk of contracting H7N9. This is due in part to their high susceptibility to contracting flu viruses during previous pandemic flu events. “This information could be crucial for public health policy decision makers in targeting priority ethnic groups for immunization programs” according to the lead author Dr. Venkata Duvvuri, a research scientist at York University’s Centre for Disease Modelling. This study was published in PLoS One on March 7, 2014.
This new H7N9 virus is genetically different form from the previously reported human influenza A virus subtypes, H1N1, 2009 H1N1, H2N2, and H3N2. Hence, the current seasonal flu vaccine cannot provide protection from the H7N9. An immunological study in China revealed the absence of cross-protective antibodies in human populations against H7N9 because of its novel genetic nature. Thus, if exposed to the H7N9 virus, the human immune system may not be ready to induce cross-protective antibodies to prevent infection – explaining why humans are at high risk of contracting H7N9. In the absence of antibodies, the T-cells play a critical role in protecting against novel flu strains based on the very similar (conserved) and shared segments of viral proteins (called epitopes) between the new flu virus and earlier (old) flu viruses. The human immune system has a remarkable ability to memorise previous flu viruses by recognizing the epitopes. T-cells recognize epitopes when they are bound to molecules related to the immune function called Human Leucocyte Antigens (HLA). This epitope-specific memory T cells attenuated the disease severity during the 2009 H1N1 virus pandemic (though it is a novel flu strain) in the absence of antibodies. Hence, it is important to assess preexisting T-cell immunity in the human population against the H7N9 virus. In addition, determining the vulnerability of different ethnic populations to H7N9 infection is critical for public health planning.
The research project was funded by the Canada Research Chairs program, the Natural Sciences and Engineering Research Council of Canada and International Development Research Centre. “We have been developing our Centre’s capacity to perform immunoinformatics and evolutionary genomics analyses of emerging viruses, and this work shows how this capacity has transformed into research outcomes with significant potential for policy impact”, said Dr. Jianhong Wu, the Director of the Centre for Disease Modelling.
Duvvuri VR, Duvvuri B, Alice C, Wu GE, Gubbay JB and Wu J. (2014) Preexisting CD4+ T-Cell Immunity in Human Population to Avian Influenza H7N9 Virus: Whole Proteome-Wide Immunoinformatics Analyses. PLoS ONE 9(3): e91273. doi:10.1371/journal.pone.0091273.