AFD - Has mass HPAI poultry vaccination driven us into a corner? H5N1, H5N2, H5N3, H5N6, H5N5, H5N8

[sharon sanders]

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 (seeEID 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.

Discussion
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.
<SNIP>
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.


Posted by Michael Coston at 7:46 AM
Labels: Poultry, reassortment, Vaccine

[Emily]

And now the US is considering using an H5N2 vaccine in development:

http://www.reuters.com/article/2015/...0ND0AI20150422

In the case of China, they vaccinate against an H5N1 strain that can infect humans, with serious illness produced in at least some people. They don't have the huge corporate poultry operations there willing to subject flocks to mass extermination with cruel foams that take minutes to suffocate them, so China felt it best to use a vaccine.

The H5N2 strain that may have evolved from vaccine pressure is an improvement since it does not sicken people. But what if now in the US we drive H5N2 evolution into something worse again, perhaps worse than the H5N1 strain in Asia?

[Emily]

I don't think the information I had about the driving force behind AI vaccination in China was correct. Not all farmers were enthused.

The government has required 100% vaccine coverage in domestic poultry, and financial support from the government ensures the implementation of this strategy. However, many farmers lack the enthusiasm to use the vaccine. They complain of low quality vaccines containing suboptimal concentration of antigens that are passed the quality guarantee dates. In addition, inactivated vaccines induce an antibody peak at least 14 days after immunization [24]. The short growing period of meat poultry and vaccine residues in the tissue of immunized poultry restrict its comprehensive usage in poultry meat production.

http://engineering.cae.cn/fase/article/2014/2095-7505/11914

Some farmers did embrace vaccination:

In addition, many low level biosecurity farms ignore effective management strategies and readily use vaccine to prevent diseases

[JJackson]

Mike thanks for being that broken record. I know it is a thankless task having to continually point out the obvious.

If you introduce selective pressure on a quasi-species, like AI, it is inevitably going to promote those strains within the host that diverge from the vaccine target. If variations about the norm are approximately normally distributed, and the vaccine is a perfect match to the mean, then the inevitable consequence is the change from a 'normal distribution' with a Dromedary hump to a Bactrian form with two humps (the middle having been selected against by the vaccine).

[Pathfinder]

USDA Questions and Answers: Biology of Avian Influenza and Recent Outbreaks

May 2015

Excerpt:

Q. Is USDA developing a vaccine that can be used for these HPAI outbreaks?

A. Yes. SEPRL does vaccine seed strain development and testing as a routine research activity. SEPRL is
developing a vaccine seed strain for potential emergency use, which would be designed to give optimal
protection in poultry, but it is too early in the development process. SEPRL scientists have developed a
candidate vaccine seed strain for an inactivated vaccine that currently is being tested. There are several
steps in the development process. USDA cannot have a vaccine considered for use in the field until it is
shown to work in the experimental studies in the laboratory. USDA SEPRL does not manufacture avian
influenza vaccines nor decide when or if they should be used in field. APHIS decides use based on need.

Q. Has USDA used avian influenza vaccines in the past?

A. USDA has not used vaccines against highly pathogenic avian influenza. However, it has been used
against low pathogenic avian influenza. The last use of H7 vaccine was in 2003 and H5 vaccine in the
1990s against.

Q. When will USDA have a vaccine for the current outbreaks ready?

A. Vaccine development occurs in many stages and because the next steps are dependent on the
outcomes of these stages, USDA cannot predict when the vaccine has reached the stage for use in
poultry. USDA will provide an update as soon as the SEPRL researchers have finished the project.

Q. Will the poultry vaccine be effective against HPAI H5N2, HPAI H5N8 or the ?novel? HPAI H5N1?

A. Because most of the protection from influenza vaccines comes from antibodies to the hemagglutinin
protein, SEPRL is working to make a single vaccine that will provide protection to all the variants that the
scientists are seeing, including HPAI H5N8, H5N2, and ?novel? H5N1. All of these variants share the
same hemagglutinin gene while differing in some the other genes.

http://www.usda.gov/documents/avian-influenza-biology-outbreaks-qa.pdf

[Emily]

This strongly supports Mike's position:

• G. J. D. Smith, X. H. Fan, J. Wang, K. S. Li, K. Qin, J. X. Zhang, D. Vijaykrishna, C. L. Cheung, K. Huang, J. M. Rayner, J. S. M. Peiris, H. Chen, R. G. Webster, and Y. Guan

Emergence and predominance of an H5N1 influenza variant in China PNAS 2006 103 (45) 16936-16941; published ahead of print October 30, 2006, doi:10.1073/pnas.0608157103
Emergence and predominance of an H5N1 influenza variant in China
Abstract The development of highly pathogenic avian H5N1 influenza viruses in poultry in Eurasia accompanied with the increase in human infection in 2006 suggests that the virus has not been effectively contained and that the pandemic threat persists. Updated virological and epidemiological findings from our market surveillance in southern China demonstrate that H5N1 influenza viruses continued to be panzootic in different types of poultry. Genetic and antigenic analyses revealed the emergence and predominance of a previously uncharacterized H5N1 virus sublineage (Fujian-like) in poultry since late 2005. Viruses from this sublineage gradually replaced those multiple regional distinct sublineages and caused recent human infection in China. These viruses have already transmitted to Hong Kong, Laos, Malaysia, and Thailand, resulting in a new transmission and outbreak wave in Southeast Asia. Serological studies suggest that H5N1 seroconversion in market poultry is low and that vaccination may have facilitated the selection of the Fujian-like sublineage. The predominance of this virus over a large geographical region within a short period directly challenges current disease control measures.

http://www.pnas.org/content/103/45/16936.abstract

Pathogen evolution in a vaccinated world
Andrew F. Read

http://www.thereadgroup.net/wp-content/uploads/Read%26MackinnonStearns%26KoelleaChap11.pdf