Wednesday, August 02, 2017

Virology: Selection Of Antigenic Variants Of An H5N1 HPAI Virus In Vaccinated Chickens


For most of the world, the use of quarantine and culling - long recommended by the OIE (see OIE: Countries That Vaccinate Poultry Need An `Exit Strategy') - is the accepted method of dealing with Highly Pathogenic Avian Influenza (HPAI) viruses. 

While still discouraging their use, a couple of years ago the OIE softened the language in their recommendations to allow:
`In short, vaccination should be implemented when culling policies cannot be applied either because the disease is endemic and therefore widely present, or the infection in affected animals is too difficult to detect.'
Although vaccines may seem an attractive option - particularly in regions with high food insecurity - experience has shown that poultry vaccines aren’t necessarily 100% effective in preventing infection; sometimes only masking the symptoms (see New Scientist: The Downsides To Using HPAI Poultry Vaccines).
This can allow viruses to spread asymptomatically through vaccinated flocks - and while that may spare the poultry industry huge losses - humans may be unknowingly exposed, and these `stealthy' viruses may continue to mutate and evolve into new strains or new subtypes (via reassortment).

As we’ve discussed previously (see PLoS Bio: Imperfect Poultry Vaccines, Unintended Results & The HPAI Poultry Vaccine Dilemma), despite more than a decade of heavy use, poultry AI vaccines have not been exactly a panacea for avian flu around the world. 
Five years ago, China had but one HPAI virus of genuine concern; H5N1. Today China – which uses 90% of the world’s supply of HPAI vaccines (cite) - has a growing array of AI subtypes (H5N6, H5N8, H7N9, H5N2, H5N3, H10N8, etc.), each sporting numerous genotypes or clades.
Over the past few years we've seen a growing number of studies strongly suggesting that the use of poultry vaccines may be at least partially responsible for this growing diversity in avian influenza viruses. A few earlier blogs include:
Subclinical Highly Pathogenic Avian Influenza Virus Infection among Vaccinated Chickens, China).
Study: Recombinant H5N2 Avian Influenza Virus Strains In Vaccinated Chickens
EID Journal: Subclinical HPAI In Vaccinated Poultry – China
Today, we can add another cautionary study:

Volume 510, October 2017, Pages 252–261

Selection of antigenic variants of an H5N1 highly pathogenic avian influenza virus in vaccinated chickens

Lam Thanh Nguyena, b, Tatsuya Nishia, 1, Shintaro Shichinohea, 2, Duc-Huy Chua, Takahiro Hionoa, Keita Matsunoa, c, Masatoshi Okamatsua, Hiroshi Kidac, d, Yoshihiro Sakodaa, c, ,

Vaccination in chickens induced the selection of antigenically drifted H5 HPAIVs.
• Antigenic drift occurred despite updating the vaccine strain.
• Residues 179 and 256 in the HA were responsible for antigenic drift.


Vaccination-primed immunity in poultry has been suggested for selection of antigenically drifted highly pathogenic avian influenza viruses (HPAIVs). In this study, we performed two consecutive passage studies of an H5N1 HPAIV in vaccinated chickens, namely, study-I and study-II, to select antigenic variants under immune pressure from the vaccination.
In study-I, nine consecutive passages of a wild-type H5N1 HPAIV were carried out in chickens vaccinated with the homologous challenge strain. Antigenically drifted variants with mutations at position 179 in the hemagglutinin (HA) were selected after three passages. Similarly, in study-II, a vaccination-mediated antigenic variant isolated in study-I was used as the vaccine and challenge strain to confirm further antigenic drift after updating the vaccine; after the third passage, additional antigenic variants with a mutation at position 256 in the HA were selected.
Thus, our study demonstrated the contribution of vaccination in the selection of antigenic variants of H5 HPAIVs in chickens.
China, which is arguably too dependent upon poultry vaccines to change policies now, has decided to roll out a new combination HPAI H5 + H7 vaccine this summer (see China MOA Orders HPAI H7N9 Vaccine Deployed Nationwide This Fall) in hopes that it will help curb their rapidly evolving H7N9 virus, as well as reining in their growing number of HPAI H5 viruses.
A lot is riding on how well this new vaccine protects poultry, how effectively it is deployed, and how (or if) it influences the future evolution of both H5 and H7 viruses.  All questions we may not know the answers to for months, or perhaps even years.
Stay tuned.

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