Wednesday, March 04, 2015

Study: Recombinant H5N2 Avian Influenza Virus Strains In Vaccinated Chickens


Photo Credit – FAO


# 9780


At the risk of sounding like a broken record, we’ve another study today that has documented multiple novel, recombinant H5N2 avian flu viruses circulating in vaccinated Chinese poultry.


China, which has relied predominantly on a poultry vaccination policy to control avian flu, has managed to protect their poultry flocks from excess mortality and morbidity, but – as we discussed previously (see EID Journal: Subclinical HPAI In Vaccinated Poultry – China – now finds itself with multiple clades and subtypes of HPAI in circulation and a roster of poultry vaccines that are slowly losing their effectiveness.


This isn’t just a problem in China, as we’ve seen similar results in Egypt (see Egypt: A Paltry Poultry Vaccine) and  Indonesia (see Indonesia: Debate Over Poultry Vaccination) as well.  


While quarantine and aggressive culling is the recommended HPAI control strategy, for countries with high food insecurity and a heavy reliance upon poultry, vaccines have long been an attractive option   And for the past decade they have been heavily employed in nations where bird flu has become endemic.


According to 2012’s Impact of vaccines and vaccination on global control of avian influenza by David Swain, more than 113 billion poultry vaccine doses were used from 2002 to 2010. Five countries accounted for 99% of vaccine used: 1) China (90.9%), 2) Egypt (4.6%), 3) Indonesia (2.3%), 4) Vietnam (1.4%), and 5) Hong Kong Special Administrative Region (< 0.01%).


The problem comes when these vaccines are either improperly applied, or not updated to deal with constantly evolving flu strains, which can drive the creation of vaccine-escape variant viruses.   


A task that becomes more difficult every year as the number of new, reassortant viruses increase.

The OIE (World Organization For Animal Health) has been long aware of the potential of vaccines to hide infection, and potentially drive viral evolution, warning that vaccination of poultry cannot be considered a long-term solution to combating the avian flu virus.


In 2009 the OIE advised:

The use of vaccination could last several years; however it will only be effective if it is applied to all poultry (chickens, hens, ducks, turkeys, geese, quails…) and through appropriate methods, particularly the use of a permanent cold chain. Vaccines should be produced in accordance with international quality standards prescribed in the OIE manual of diagnostic tests and vaccines for terrestrial animals.

As soon as national Veterinary Services are fully operational for early detection and rapid response using biosecurity measures in infected premises vaccination must be stopped; it is not recommended to use vaccination as a long term control measure since very often it contributes to hide the presence of the virus.

Any vaccination campaign must include an “exit strategy” i.e. a return to classic disease control measures.

In 2013, the OIE reiterated this advice in Questions and Answers on influenza A(H7N9), stating:


Does OIE recommend vaccination of animals to control the disease?

When appropriate vaccines are available, vaccination aims to protect the susceptible bird populations from potential infection. Vaccination reduces viral excretions by animals and the virus’ capacity to spread. Vaccination strategies can effectively be used as an emergency effort in the face of an outbreak or as a routine measure in an endemic area. Any decision to use vaccination must include an exit strategy, i.e. conditions to be met to stop vaccination.

Despite these warnings, none of the nations that now use 99% of the world’s poultry vaccines appear willing (or able) to move towards that recommended `exit’.  


First, a link and some excerpts  from a recently published open-access study in Viruses, after which I’ll return with a bit more:


Genomic and Phylogenetic Characterization of Novel, Recombinant H5N2 Avian Influenza Virus Strains Isolated from Vaccinated Chickens with Clinical Symptoms in China

Huaiying Xu, Fang Meng , Dihai Huang , Xiaodan Sheng, Youling Wang, Wei Zhang , Weishan Chang , Leyi Wang   and Zhuoming Qin

View Full-Text   |   Download PDF [1601 KB, uploaded 25 February 2015]   |   Browse Figures

Abstract: Infection of poultry with diverse lineages of H5N2 avian influenza viruses has been documented for over three decades in different parts of the world, with limited outbreaks caused by this highly pathogenic avian influenza virus. In the present study, three avian H5N2 influenza viruses, A/chicken/Shijiazhuang/1209/2013, A/chicken/Chiping/0321/2014, and A/chicken/Laiwu/0313/2014, were isolated from chickens with clinical symptoms of avian influenza.

Complete genomic and phylogenetic analyses demonstrated that all three isolates are novel recombinant viruses with hemagglutinin (HA) and matrix (M) genes derived from H5N1, and remaining genes derived from H9N2-like viruses. The HA cleavage motif in all three strains (PQIEGRRRKR/GL) is characteristic of a highly pathogenic avian influenza virus strain.

These results indicate the occurrence of H5N2 recombination and highlight the importance of continued surveillance of the H5N2 subtype virus and reformulation of vaccine strains.



In this study, three H5N2 influenza virus strains isolated from chickens were identified as novel reassortants with a highly pathogenic viral genotype. Surprisingly, the affected birds had been vaccinated with killed influenza vaccines but still showed characteristic clinical symptoms of avian influenza and eventually died.

These results are in agreement with previous work indicating that AIVs can continue genetic evolution under vaccination pressure [20]. Moreover, this study highlights the importance and necessity of periodic reformulation of the vaccine strain according to the strains circulating in the field in countries where vaccines are applied to control avian influenza.

Therefore, we recommend that routine surveillance to monitor the influenza viral evolution in the field be carried out in combination with a comprehensive control program and vaccination as opposed to vaccination programs alone.

(Continue. . . )


The `elephant in the room’ is that 10 years ago, when most of these countries elected to rely primarily on poultry vaccinations to control H5N1, there was only one HPAI H5 virus of concern; H5N1.   Now we now have at least a half dozen subtypes (H5N1, H5N2, H5N3, H5N6, H5N5,  H5N8) and literally dozens of clades between them.

This rapid growth is likely due in no small part to the continued use of outdated, poorly matched poultry vaccines which only hid symptoms in birds, and allowed viruses to continue to circulate and reassort. 


But it isn’t just me saying that.  Last November the EID Journal dispatch Subclinical Highly Pathogenic Avian Influenza Virus Infection among Vaccinated Chickens, China  addressed these concerns, and suggested a way forward:


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.


We propose that the only way out of this dilemma is to strengthen the strategy published previously, which covers the following components: education, biosecurity, rapid diagnostics and surveillance, and elimination of infected poultry (14). Mass vaccination should be used as an additional tool within this 4-component strategy, not in place of the 4 components.


Supposedly the definition of insanity is doing the same thing over and over again and expecting different results.

While a case can be made for the continued use of poultry vaccines in countries where these viruses are raging, a pattern of increasing risks and decreasing returns makes it imperative that modifications to these strategies are made before we vaccinate ourselves into a very unenviable corner.