While I had not planned on doing two H9N2-centric blogs in a row, overnight China's MOA published a remarkable announcement - which tacitly admits that many of their current animal vaccines (including against H9N2) are inadequate and/or suboptimal - and orders major regulatory changes in order to accelerate updates.
As we discussed yesterday in EM&I: Enhanced Replication of a Contemporary Avian Influenza A H9N2 Virus in Human Respiratory Organoids - despite near universal vaccination - H9N2 is poorly controlled in China's poultry, and it continues to spill over into humans.
This is not a new revelation, as over 4 years ago we looked at J. Virus Erad.: Ineffective Control Of LPAI H9N2 By Inactivated Poultry Vaccines - China, which warned that their current inactivated vaccines were no match against this rapidly evolving pathogen.
Last April, in NPJ Vaccines: Impact of Inactivated Vaccine on Transmission and Evolution of H9N2 Avian Influenza Virus in Chickens, we saw evidence that not only had inactivated vaccines failed to prevent - or even reduce - H9N2 in China's poultry, they may have driven viral evolution (including mammalian adaptations).This problem extends beyond H9N2, as 2014's EID Journal dispatch Subclinical Highly Pathogenic Avian Influenza Virus Infection among Vaccinated Chickens, China addressed similar concerns with HPAI H5 (bolding mine):
HPAI mass vaccination played a crucial role in HPAI control in China. However, this study demonstrated multiple disadvantages of HPAI mass vaccination, which had been suspected (13,14). For example, this study showed that H5N1 subtype HPAI virus has evolved into multiple H5N2 genotypes, which are all likely vaccine-escape variants, suggesting that this virus can easily evolve into vaccine-escape variants.
This observation suggests that HPAI mass vaccination, which is highly effective in the beginning of an outbreak, may lose its effectiveness with time unless the vaccine strains are updated. Moreover, this study showed that vaccinated chicken flocks can be infected with vaccine-escape variants without signs of illness.
As the world contemplates moving towards more aggressive vaccination of poultry against avian influenza, it must also accept that once we begin, we need to devote considerable and continual time, energy, and resources in order to keep vaccines current.
Otherwise, we risk making matters worse.
The Chinese announcement (MOA No. 962) calls for major changes in the way that new vaccine updates are produced, and approved, in China. While the primary focus of this document is obviously LPAI H9N2, they list 27 animal pathogen vaccines in its appendix.
The intent is to reduce the time it takes to develop, approve, and deploy new updates to animal vaccines; from several years to a matter of months. This would almost certainly involve some trade-offs, particularly in the amount of pre-release testing of updates that would be required.
Of course, continuing to use existing, ineffective vaccines, is problematic in its own right.
The glacial pace of updating agricultural vaccines is not just a problem in China, as we've seen similar issues around the globe, including:
- In 2012's Egypt: A Paltry Poultry Vaccine, researchers examined the effectiveness of six commercially available H5 poultry vaccines used in Egypt and found only one actually appeared to offer protection.
- Six years later, another study (see Sci. Reports: Efficacy Of AI Vaccines Against The H5N8 Virus in Egypt) found `. . . most of the commercial poultry H5 vaccines used in the present study were ineffective. . . '
- in 2023's WUR: 2 of 4 H5 Poultry Vaccines Tested Appear Effective Against H5N1, researchers in the Netherlands found ineffective vaccines were still being marketed.
But the devil is always in the details.
Not only do we need effective (and continually updated) avian flu vaccines, we need ways to ensure they are being properly and consistently applied, along with greatly enhanced surveillance and testing of vaccinated flocks (looking for breakthrough infections), including quarantine and culling if necessary.
None of this will be cheap, or easy. But doing anything less risks making a bad situation far worse in the long run.
Sadly, our 20+ year track record of poultry vaccine stewardship, has not been encouraging.