J Virol. Divergent H7 immunogens offer protection from H7N9 challenge

[Giuseppe]

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]


Divergent H7 immunogens offer protection from H7N9 challenge

Florian Krammer 1*, Randy A. Albrecht 1,2, Gene S. Tan 1, Irina Margine 1,3, Rong Hai 1, Mirco Schmolke 1,2, Jonathan Runstadler 4, Sarah F. Andrews 5, Patrick C. Wilson 5, Rebecca J. Cox 6, John J. Treanor 7, Adolfo Garc?a-Sastre 1,2,8* and Peter Palese 1,8

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

Published ahead of print 22 January 2014, doi: 10.1128/JVI.03095-13 <CITE>JVI.03095-13 </CITE>
<CITE></CITE>
<CITE></CITE>
<CITE></CITE>ABSTRACT

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.


FOOTNOTES

*To whom correspondence should be addressed: florian.krammer@mssm.edu
*adolfo.garcia-sastre@mssm.edu

Copyright ? 2014, American Society for Microbiology. All Rights Reserved.


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[NS1]

Re: J Virol. Divergent H7 immunogens offer protection from H7N9 challenge

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]


Divergent H7 immunogens offer protection from H7N9 challenge

Florian Krammer 1*, Randy A. Albrecht 1,2, Gene S. Tan 1, Irina Margine 1,3, Rong Hai 1, Mirco Schmolke 1,2, Jonathan Runstadler 4, Sarah F. Andrews 5, Patrick C. Wilson 5, Rebecca J. Cox 6, John J. Treanor 7, Adolfo García-Sastre 1,2,8* and Peter Palese 1,8

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

Published ahead of print 22 January 2014, doi: 10.1128/JVI.03095-13 <CITE>JVI.03095-13 </CITE>
<CITE></CITE>
<CITE></CITE>
<CITE></CITE>ABSTRACT

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.


FOOTNOTES

*To whom correspondence should be addressed: florian.krammer@mssm.edu
*adolfo.garcia-sastre@mssm.edu

Copyright © 2014, American Society for Microbiology. All Rights Reserved.


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Yes or No​

At the emergence of H7N9 during early 2013 in China, multiple groups of Western public health and academic researchers profiled the standing H7 vaccines and sweepingly disapproved them for effectiveness against H7N9. Today, while the threat blooms almost one year later and after those organisations have not developed medical advances to protect the public, the standing deans spring into action to anoint the old, previously disapproved, vaccines and bless them for "first line" defense?

Religion is a belief based system of thinking that may drive outcomes more strongly than a fact-based position. The biological mechanism of a vaccine is certainly not affected by mere faith, but apparently vaccine science policy is. A more faithful herd cannot be found. When critical examination has previously led to refusal, but later turns to optimism, on evidence that is unchanged, take note that a faith bias is implicit to the speaker. Observe a tribal religion at play, but don't call it science.

We depend on these labs for observation-based conclusions, not positions malleable to the political winds and driven by faith-based perogatives. Conclusions that are convenient to any political crisis are just that, convenient, useful for a moment. Being caught with no battle strategy and no arsenal is an embarrassment, but foisting on the public a deployment around maps of the 1812 campaign armed only with warped kegs of wet powder, now that hints at a misguided and misguiding general leadership.

An accurate and durable finding on this matter from the research community, separate from political exigencies, would be valuable. Do these vaccines effectively prevent infection for any of the 3 or more current lineages of Emergent H7N9?

Yes or No?

 

[JJackson]

Re: J Virol. Divergent H7 immunogens offer protection from H7N9 challenge

NS1 have you, or anyone else, read the full paper? What tests did they do to come to the conclusion that H7's produce good cross reactive immunity? And for that matter what did the first lot do to come to the opposite conclusion? As a human flu proxy lab mice are a cost effect model but I would not bet the house on results being directly transferable to humans.

The WHO seem to be pushing A\Anhui\1\2013(H7N9) as the candidate seed strain, which was one of the first released sequences, and, looking at the sequence data this seem to still be a high homology match. That said should this sero-type go pandemic it may well be due to a critical change which may leave the pandemic form significantly different, antigenically, to anything we have yet met.