Wednesday, February 18, 2015

JCI: Preexisting Human Antibodies Neutralize H7N9 influenza strains


Credit NIAID


# 9724


Based on some of the press coverage overnight (see below) one could be forgiven for coming away with the impression that if you’ve gotten the flu shot recently, you are probably immune to the avian H7N9 flu.


But of course, things are never as simple as the headline writers would have us believe.

First, this excerpt from Agence France-Presse.


Flu shot protects against new strain H7N9: study

February 18, 2015 12:02pm

29 7 0 38

The flu vaccine may not have protected most people against influenza circulating widely this season, but a study Tuesday showed it was effective against the new H7N9 strain that emerged in China in 2013.

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Pretty definitive, and this story provides little in the way of caveats, although at one point (near the end) it quotes study author Carole Henry as saying,  "Although they are not always protective, H7-reactive antibodies can be found in almost everyone that's been vaccinated."

Not mentioned in this report, however, are the sticky little details that the level of  H7N9 cross-reactive antibodies created by the seasonal flu shot are fairly low, and the amount of protection they would convey to humans is unknown.

While we are reassured that  `three antibodies appeared to completely neutralize H7N9 avian flu’, less clear are the facts that these antibodies were only tested in vitro and in mice


While valid test methods, neither are fully predictive of human physiological responses.


Despite the media’s ambitious interpretation, the study makes no claims as to the level of serum protection in the general population against H7N9 due to previous flu vaccinations.


A far more balanced report on this study can be found on Live Science, by Rachel Rettner (see Flu Shot May Give You a Boost Against Bird Flu), where she quotes one of the study’s authors:


Still, it's not known whether the level of antibodies seen in the study participants would be enough to provide full protection against an H7N9 infection. Wilson said he suspects that vaccination with a seasonal flu shot would not fully protect against H7N9, but that if those vaccinated did become infected with the virus, these "cross reactive" antibodies might improve their situation, for example, by reducing how long they are sick or how ill they become.


In other words, a history of taking the seasonal flu vaccine might provide an `edge’ against novel flu infection that someone with a more immunologically naive system might not have.  


The key finding here is not that we are all already protected against H7N9, but that the seasonal flu shot generates small amounts of broadly neutralizing  antibodies which – if preferentially amplified – might lead to more effective therapies against a broad range of novel flu strains.  


As an added bonus, some of us may already carry some small level of cross-reactive antibodies which might help reduce the impact of an H7N9 infection.


From a University of Chicago press release:


Seasonal flu vaccine induces antibodies that protect against H7N9 avian flu

Study identifies antibodies isolated from individuals with seasonal flu vaccinations that neutralize H7N9 and other influenza strains

February 17, 2015


Despite the efficacy of these antibodies, it is still unclear why they are produced in relatively low amounts. The team is now working to better understand this process and to develop therapeutic approaches based on these antibodies.

"The challenge is to exploit this response on a larger scale to make vaccines or therapeutics that offer broad protection against influenza strains," Wilson said. "For now, it's clear that seasonal flu vaccination provides defense against more than just common strains. Everyone should be vaccinated."

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Below is a link to the actual study, which is available in its entirety online.


Preexisting human antibodies neutralize recently emerged H7N9 influenza strains

Carole J. Henry Dunand1, Paul E. Leon2,3, Kaval Kaur1,4, Gene S. Tan2, Nai-Ying Zheng1, Sarah Andrews1, Min Huang1, Xinyan Qu1, Yunping Huang1, Marlene Salgado-Ferrer1, Irvin Y. Ho1, William Taylor1, Rong Hai2, Jens Wrammert5, Rafi Ahmed5, Adolfo García-Sastre2,6,7, Peter Palese2,6, Florian Krammer2 and Patrick C. Wilson1,4

Published February 17, 2015
Submitted: July 21, 2014; Accepted: January 6, 2015.

The emergence and seasonal persistence of pathogenic H7N9 influenza viruses in China have raised concerns about the pandemic potential of this strain, which, if realized, would have a substantial effect on global health and economies. H7N9 viruses are able to bind to human sialic acid receptors and are also able to develop resistance to neuraminidase inhibitors without a loss in fitness. It is not clear whether prior exposure to circulating human influenza viruses or influenza vaccination confers immunity to H7N9 strains.

Here, we demonstrate that 3 of 83 H3 HA-reactive monoclonal antibodies generated by individuals that had previously undergone influenza A virus vaccination were able to neutralize H7N9 viruses and protect mice against homologous challenge. The H7N9-neutralizing antibodies bound to the HA stalk domain but exhibited a difference in their breadth of reactivity to different H7 influenza subtypes. Mapping viral escape mutations suggested that these antibodies bind at least two different epitopes on the stalk region.

Together, these results indicate that these broadly neutralizing antibodies may contribute to the development of therapies against H7N9 strains and may also be effective against pathogenic H7 strains that emerge in the future.

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