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Starting in the spring of 2013, and continuing for the next 4 years, China was embroiled in an LPAI H7N9 epidemic (see chart below), which unlike H5, produced little or no illness in birds, but could be deadly in humans.
Being asymptomatic in poultry, it made control (and human avoidance) of the virus difficult.
By the summer of 2017 - with China, and the world, fearing that H7N9 was on the verge of sparking a wider pandemic - Chinese scientists rolled out a new, experimental H5+H7 poultry vaccine across all of China.
While previous poultry vaccination programs had yielded varying levels of success, China's dramatic drop in human infections, outbreaks in poultry, and virus detection from routine surveillance exceeded all expectations.
Of course, this vaccine did not eradicate H5 and H7 viruses in China, as they continued to circulate and evolve in wild birds and unvaccinated poultry. While H7N9 remains largely suppressed, HPAI H5 viruses (primarily H5N6 & H5N1) have made a significant comeback since 2020.
- In 2021, in EID Journal: Novel Reassortant Avian Influenza A(H5N6) Virus, China, 2021, Chinese researchers described novel reassortants of H5N6 as moving away from the protection of China's poultry vaccines, and warned its transmission risk was likely to increase.
- In 2020, we saw EID Journal: Evolution and Antigenic Drift of Influenza A (H7N9) Viruses, China, 2017–2019, which further described the post-vaccination evolution of H7N9.
- In 2019's 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 were already spreading in several regions of China.
A reminder that no matter how good a vaccine might be, evolutionary processes begin to erode their effectiveness almost immediately. To remain protective, poultry vaccines must be continually updated, and even then, what happens in unvaccinated birds is impossible to control.
With H5N1 on the rise around the globe, many countries - heartened by China's success - are either exploring or are already embracing the use of H5 poultry vaccines to protect their poultry industry.
Poorly matched vaccines, however, can help drive viral evolution and have the potential to make matters worse (see MPR: Poultry AI Vaccines Are Not A `Cure-all’ & New Scientist: The Downsides To Using HPAI Poultry Vaccines).
While some countries are being cautious - and are testing vaccines for their effectiveness (see WUR: 2 of 4 H5 Poultry Vaccines Tested Appear Effective Against H5N1) - others have decided to use existing vaccines.
Meanwhile, the panoply of H5 viruses in the wild continue to evolve and diversify, making it more difficult to devise a one-vaccine-fits-all solution.
All of which brings us to a Dispatch, published this week in the CDC's EID Journal, which warns of novel H5N1 viruses detected in dead birds in China which already display a low antigenic reaction to vaccine antiserum.
This is highly technical report, so I've only posted some brief excerpts. Follow the link for the complete readout of what they found. But the short version is, the continually evolving array of H5 viruses may not be long deterred by our current batch of poultry vaccines.
Novel Avian Influenza Virus (H5N1) Clade 2.3.4.4b Reassortants in Migratory Birds, China
Jing Yang1, Chunge Zhang1, Yue Yuan1, Ju Sun1, Lu Lu1, Honglei Sun, Heting Sun, Dong Chu, Siyuan Qin, Jianjun Chen, Chengbo Zhang, Xiyan Hao, Weifeng Shi, Wenjun Liu, George F. Gao, Paul Digard, Samantha Lycett, and Yuhai Bi
Abstract
Two novel reassortant highly pathogenic avian influenza viruses (H5N1) clade 2.3.4.4b.2 were identified in dead migratory birds in China in November 2021. The viruses probably evolved among wild birds through different flyways connecting Europe and Asia. Their low antigenic reaction to vaccine antiserum indicates high risks to poultry and to public health.
Since the Gs/GD/96-lineage highly pathogenic avian influenza virus (HPAIV) (H5N1) was identified in 1996, H5 HPAIVs have evolved into divergent clades and caused continuous outbreaks in birds (1–11). Moreover, long-distance transmissions of H5 HPAIVs within a relatively short period indicate a crucial role of migratory birds in global spread of HPAIVs (7,8).
Thus far, H5 viruses have undergone at least 4 waves of intercontinental transmission: H5N1 clade 2.2 during 2005–2006, H5N1 clade 2.3.2.1c during 2009–2010, H5N8 clade 2.3.4.4a and H5N1 clade 2.3.2.1c during 2014–2015, and H5Ny clade 2.3.4.4b during 2016–2017 (2–8).
Starting during 2020–2021, a new wave of HPAIV H5N1/H5N8 clade 2.3.4.4b outbreaks was reported in wild and domestic birds in Eurasia (9–11) and Africa (https://wahis.woah.org/#/event-management). Human cases of H5N1/H5N6/H5N8 infection were sporadically documented (https://www.who.int/teams/global-influenza-programme/avian-influenza/monthly-risk-assessment-summary), highlighting the zoonotic risk of H5 HPAIVs.
(SNIP)
In this study, we explored the genetic origin, spread patterns, and antigenicity of H5N1 viruses identified from 2 dead migratory birds in China.
(SNIP)
Current H5N1 viruses have resulted in substantial mortality in domestic and wild birds in Eurasia, Africa, and Americas (https://wahis.woah.org/#/event-management); however, they have only been identified in wild birds in mainland China.
Compared with high HI antibody titers (256) between homologous antiserum and antigens of H5 vaccines, the recent H5N1/H5N8 viruses presented low HI titers (2–16) against Re-11/Re-13 antiserum (Table 1). In addition, cluster 1 H5N8 viruses had HI titers of 64 against Re-14 (cluster 1) antiserum, whereas HI titers for the H5N1 viruses were 128 for Bs/EC/74-L2021 (cluster 2) and 32 for Ws/NC/AK1-O/2021 (cluster 3).
This finding indicates lower antigenic identities between H5N1/H5N8 viruses circulating in wild birds and vaccines used in domestic poultry, even within the same clade. This antigenic variation may correlate to substitutions at antigenic sites (Table 2; Appendix 2 Tables 3,4, Figure 3).
In conclusion, we identified 3 H5N1 HPAIVs in wild birds in autumn 2021, China. The antigenic divergence highlights the high-risk introduction of H5N1 circulating in wild birds to incompletely protected vaccinated flocks in China. The H5N1 viruses have experienced complicated reassortment during long-distance spread through various bird migration routes. Therefore, we call for international cooperation on AIV monitoring in migratory birds to help early identification and intervention of the emerging and reemerging AIVs with public health risks.
Dr. Yang is an assistant professor at the Institute of Microbiology, Chinese Academy of Sciences. Her research interests are focused on the evolution and spread patterns of emerging and reemerging infectious diseases.
While no one can predict the future course of HPAI H5 - or any other emerging infectious disease for that matter - there is one constant that we can be sure of; evolution never stops.
Which is why we need to be prepared for surprises going forward. Both with H5N1, and the pandemic threats that will inevitably follow.