Tuesday, October 12, 2021

J. Virus Erad.: Ineffective Control Of LPAI H9N2 By Inactivated Poultry Vaccines - China


For a ubiquitous, low pathogenic, and seemingly innocuous avian flu virus - one that rarely infects, and mildly sickens humans - we spend an awful lot of time looking at, and trying to analyze, avian H9N2. 

But it is not without good reason, for H9N2 has shared its internal genes with - and thereby helped to create - some of the most dangerous avian flu viruses (H5N1, H7N9, H10N8) on the planet.  A few (of dozens) or studies include:

While an LPAI on its own, H9N2 is so enmeshed in the growing constellation HPAI viruses that I've occasionally called it the Professor Moriarty of avian flu viruses.  Often, when new HPAI flu strains emerge – if you look deep enough – you’ll find LPAI H9N2 was skulking somewhere in the shadows (see PNAS: Evolution Of H9N2 And It’s Effect On The Genesis Of H7N9).

In May of 2020, the CDC added a new lineage (H9N2 Y280 lineage [A/Anhui-Lujiang/13/2018]) to their short list of novel flu viruses with at least some pandemic potential, although it would not be expected to gave the same impact as an H5 or H7 avian flu. 

While originally relegated pretty much to Asia, over the past decade we've seen H9N2 expand to the Middle East and into the African Continent (see Viruses: A Global Perspective on H9N2 Avian Influenza Virus).

Range Of Endemic H9N2 Viruses

This global expansion comes despite massive efforts in China, Egypt, and a few other other countries to control the virus via poultry vaccination. We've seen those poultry vaccination programs loose effectiveness over time however (see Egypt: A Paltry Poultry Vaccine and The HPAI Poultry Vaccine Dilemma), as the virus mutates and vaccines are not updated or uniformly deployed.

All of this has ramifications beyond H9N2, as we've recently seen the resurgence of a far more dangerous HPAI H5N6 in China, three years after a very successful nationwide deployment of a new H5+H7 poultry vaccine.   

While quarantine and aggressive culling is the recommended HPAI control strategy in most nations, for countries with high food insecurity and a heavy reliance upon poultry, vaccines have long been an attractive option  

For the past 15 years they have been heavily employed in nations where bird flu has become endemic, but not without raising concerns. In 2014 and in 2015 (see here and here) we looked at reports of vaccine escape H5 viruses in Chinese poultry. 

Three years ago, in EID Journal: Two H9N2 Studies Of Note, we looked at two reports which suggest that H9N2 continues to evolve away from current (pre-pandemic and poultry) vaccines and is potentially on a path towards better adaptation to human hosts.

All of which brings us to a study, recently published in the Journal of Virus Eradication by researchers from Shanghai Veterinary Research Institute and Wageningen University & Research, the Netherlands that finds the current inactivated virus vaccines used in China against H9N2 to be no match for this rapidly evolving pathogen. 

They warn:

The failure of vaccination might be because of inefficient application, low dose, and low vaccination coverage (especially in the household sector).11,12 Moreover, the continuing transmission in combination with the intensive long-term usage of the inactivated virus vaccine may have led to antigenic changes leading to immune escape.

 The link, and excerpts from the open access study follow. 

Vaccination with inactivated virus against low pathogenic avian influenza subtype H9N2 does not prevent virus transmission in chickens

Hongrui Cui ab Mart CMde Jongb NancyBeerensc Monique M.van Oersd Qiaoyang Tenga Luzhao Lia XuesongLia QinfangLiua ZejunLia

https://doi.org/10.1016/j.jve.2021.100055Get rights and content
Under a Creative Commons license
open access


H9N2 subtype avian influenza has spread dramatically in China ever since first reported in the 1990s. A national vaccination program for poultry was initiated in 1998. Field isolation data show that the widely used inactivated H9N2 vaccine does not provide effective control of the transmission of this low pathogenic avian influenza (LPAI) virus in poultry. 

Current research has focused on two reasons: (i) insufficient immune response triggered by the vaccination with the inactivated virus, (ii) the occurrence of escape mutants selected by vaccine-induced immune pressure. However, the lack of effectivity of the inactivated virus vaccine to sufficiently reduce transmission has been noticed. 

We mimicked the natural infection and transmission process of the H9N2 virus in vaccinated and non-vaccinated chickens. A statistical model was used to estimate the transmission rate parameters among vaccinated chickens, varying in serum hemagglutinin inhibition titers (HIT) and non-vaccinated chickens. We demonstrate, for the first time, that the transmission is not sufficiently reduced by the H9N2 vaccine, even when vaccinated chickens have an IgG serum titer (HIT>23), which is considered protective for vaccination against homologous highly pathogenic avian influenza (HPAI) virus.

Our study does, on the other hand, cast new light on virus transmission and immune escape of LPAI H9N2 virus in vaccinated chickens populations, and shows that new mitigation strategies against LPAI viruses in poultry are needed. 


5. Conclusion

In our research combining an experimental transmission study with mathematical modeling, we show that inactivated H9N2 vaccine is able to provide individual protection, but unable to stop the transmission of the H9N2 virus in chickens. The power of the statistical test used was 78%. Transmission modeling can give a statistical estimation of the vaccine effects on virus transmission in certain populations, thereby providing guidance for control strategies.

           (Continue . . . )

While poultry vaccination programs such as we've seen in China have saved countless millions of birds from being culled and in many cases - have reaped tremendous benefits - unless vaccines are frequently updated to match current viruses - and are correctly and universally applied - they can lose their effectiveness and eventually become a double-edged sword.