Thursday, January 23, 2014

Divergent H7 immunogens offer protection from #H7N9 challenge

From the American Society of Microbiology, Journal of Virology:
  1. Peter Palese1,8
+ Author Affiliations
  1. 1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  2. 2Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  3. 3Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  4. 4Department of Biological Engineering and Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA
  5. 5The Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, Illinois, USA
  6. 6Department of Clinical Science; University of Bergen; Haukeland University Hospital; Bergen, Norway
  7. 7Department of Medicine, University of Rochester Medical Center, Rochester, New York, USA
  8. 8Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA


The emergence of avian H7N9 viruses in humans in China has renewed concerns about influenza pandemics emerging from Asia. Vaccines are still the best countermeasure against emerging influenza virus infections, but the process from identification of vaccine seed strains to the distribution of the final product can take several months. In the case of the 2009 H1N1 pandemic, a vaccine was not available before the first pandemic wave hit and therefore came too late to reduce influenza morbidity. H7 vaccines based on divergent isolates of the Eurasian and North American lineage have been tested in clinical trials, seed strains and reagents are already available and can potentially be used initially to curtail influenza-induced disease until a more appropriately matched H7N9 vaccine is ready. In a challenge experiment in the mouse model we assessed the efficacy of both inactivated virus and recombinant hemagglutinin vaccines made from seed strains that are divergent to H7N9 from each of each of the two major H7 lineages. Furthermore, we analyzed the cross-reactive responses to H7N9 of sera from human subjects vaccinated with heterologous North American and Eurasian lineage H7 vaccines. Vaccinations with inactivated virus and recombinant hemagglutinin protein preparations from both lineages raised hemagglutination-inhibiting antibodies against H7N9 viruses and protected mice from stringent viral challenges. Similar cross-reactivity was observed in sera of human subjects from a clinical trial with a divergent H7 vaccine. Existing H7 vaccine candidates based on divergent strains could be used as a first line of defense against an H7N9 pandemic. In addition it also suggests that H7N9 vaccines that are currently under development might be stockpiled and used for divergent avian H7 strains that emerge in the future. 

Importance Sporadic human infections with H7N9 viruses started being reported in China in early spring 2013. Despite a significant drop in infections during the summer months of 2013, an increased number of cases has already been reported for the 2013/14 winter season. The high case fatality rate, the ability to bind to receptors in the human upper respiratory tract in combination with several family clusters and the emergence of neuraminidase inhibitor resistant variants that show no loss of pathogenicity or ability to transmit in animal models have raised concerns about a potential pandemic and have spurred efforts to produce vaccine candidates. Here we show that antigens preparations from divergent H7 strains are able to induce protective immunity against H7N9 infection. 

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