Sunday, July 19, 2020

EID Journal: Evolution and Antigenic Drift of Influenza A (H7N9) Viruses, China, 2017–2019

H7N9 Epidemic Waves - June 14th 2017 - Credit FAO


Three years ago, the most worrying pandemic threat on our radar was avian H7N9 - a much deadlier virus than SARS-CoV-2 - which emerged in Mainland China in  2013 and produced its largest human epidemic during its 5th wave (see chart above).

While not alone on the pandemic watch list, two different H7N9 viruses were placed at the very top of the CDC's IRAT (Influenza Risk Assessment Tool) list, and senior Chinese scientists  (see  NPR: A Pessimistic Guan Yi On H7N9's Evolution) expressed deep concerns over the virus's trajectory.

But in the summer of 2017, something unexpected happened.  China announced the creation of a new, experimental H5+H7 poultry vaccine - and after an abbreviated test run - ordered it deployed nationwide (see 2017's China MOA Orders HPAI H7N9 Vaccine Deployed Nationwide This Fall).

While other poultry vaccination programs - in places like Indonesia and Egypt - had fallen short, China's program proved remarkably successful. Human infections with H7N9 - along with two co-circulating H5 viruses (H5N6 & H5N1) - dropped precipitously, as did outbreaks reported in poultry. 

Furthermore, global outbreaks of H5 and H7 avian flu viruses - which often spread via migratory birds coming from China - have dropped markedly as well. 

China's remarkable success of the past 3 years is undeniable, but it is not absolute. H5 and H7 viruses still circulate in China - albeit currently at greatly suppressed levels - and vaccines have a history of losing effectiveness over time. 

In 2015's The HPAI Poultry Vaccine Dilemma, we discussed these issues, including:
  • Poultry vaccines don’t always prevent disease – sometimes they only mask the symptoms of infection - and that can not only allow viruses to spread stealthily, it can also put human health at risk.
  • Poorly matched vaccines, or those inconsistently or haphazardly applied, have been linked to driving vaccine-escape flu variants, and may be at least partially responsible for the sudden proliferation of new avian flu subtypes we’ve seen emerge over the past decade (H5N3, H5N5, H5N6, H5N8, H7N9, H10N8, etc. ).
So - since we know that vaccines can sometimes drive the creation of new variant viruses - for the past 3 years, we've been watching for any signs of new, vaccine-escape variants of H7N9 (or H5Nx), emerging in China.    

And last December, in EID Journal: Antigenic Variant of Highly Pathogenic Avian Influenza A(H7N9) Virus, China, 2019, we learned details of recently emerged antigenic variants of HPAI H7N9 that are already spreading in several regions of China.
From the author's conclusions:
In China, vaccination plays a decisive role in the prevention and control of H7N9 virus–mediated infection. Earlier mass vaccination of poultry with H7-Re1 successfully induced a sharp decline in H7N9 infection prevalence among poultry and humans.
However, as of 2019, H7N9 variants have surfaced, posing a considerable economic and public health threat and highlighting the urgent need for new antigen-matched vaccines and more productive measures to eliminate highly pathogenic H7N9 viruses.

This week we have a new report from China, published in the EID Journal, that details the evolution of H7N9 virus in China since the mass vaccination program was launched.  Once again the authors caution that H7N9 remains a threat, and calls for comprehensive surveillance and enhancement of biosecurity precautions.

Volume 26, Number 8—August 2020
Jiahao Zhang1, Hejia Ye1, Huanan Li1, Kaixiong Ma, Weihong Qiu, Yiqun Chen, Ziwen Qiu, Bo Li, Weixin Jia, Zhaoping Liang, Ming LiaoComments to Author , and Wenbao Qi 


After a sharp decrease of influenza A(H7N9) virus in China in 2018, highly pathogenic H7N9 viruses re-emerged in 2019. These H7N9 variants exhibited a new predominant subclade and had been cocirculating at a low level in eastern and northeastern China. Several immune escape mutations and antigenic drift were observed in H7N9 variants.

Since emerging in China in 2013, influenza A(H7N9) viruses have continued to circulate in mainland China, sporadically causing human infection (1–3). As of February 2020, a total of 1,568 laboratory-confirmed human cases and 616 related deaths had been reported, for a fatality rate of ≈40% (LINK)  

In mid-2016, a highly pathogenic avian influenza (HPAI) virus of subtype H7N9 emerged, and the number of cases in humans began to rise sharply during a fifth wave (4,5). Animal studies indicated that these HPAI H7N9 viruses are highly virulent in chickens and have gained transmissibility among ferrets (5–7). Also, the cocirculation of HPAI (H7N9) viruses caused high genetic diversity and host adaption (8), posing public health concerns.

Although HPAI H7N9 viruses spread widely across China in 2017 (8,9), after an influenza H5/H7 bivalent vaccine for poultry was introduced in September 2017, the prevalence of the H7N9 viruses in birds and humans decreased dramatically (6,10). In early 2019, when the novel HPAI H7N9 viruses re-emerged, the isolation of HPAI H7N9 viruses from birds revealed them to be responsible for continuous epidemics in northeastern China (11).
In March 2019, a human death in Gansu, China, was confirmed to have been caused by an H7N9 virus (12). To explore the prevalence and evolution of influenza A(H7N9) viruses, we sequenced 28 hemagglutinin (HA) and neuraminidase (NA) genes of poultry-origin H7N9 viruses circulating in China during 2019.


China has proven that the rapid and thorough application of a well-matched poultry vaccine can quickly subdue a raging avian flu epidemic, but at the same time the virus has demonstrated its ability to counter by generating vaccine-escape variants. 

Essentially, China is now engaged in an `arms race' with the virus, and must continually re-engineer and redeploy new vaccines in order to keep up with H7N9's evolution (and H5Nx's). 
As long as they can keep up, China can probably keep a lid on the situation. But keeping up requires a huge commitment of money and resources, and getting it right 100% of the time.  A tall order in ordinary times, but made even tougher by our current pandemic situation, a global economic crisis, extensive flooding across Mainland China, and other pressing matters.   

Today's report is another reminder that victories against novel disease threats can be fleeting, and that even as we struggle against COVID-19, nature's laboratory continues to churn out new potential threats.

As unsporting as it would be for nature to unleash another pandemic before COVID-19 has run its course, nature doesn't care.  We need to come to terms with that, and begin to treat pandemics as being every bit as much of a national security issue as terrorism or national defense.