Avian Influenza (Bird Flu) Poultry Vaccines
Introduction
Transmission of bird flu (H5 N1)to humans and consequent human-to-human transmission has been declared a serious global health threat. Part of a control strategy for bird flu is the vaccination of poultry flocks provided vaccinated birds can be distinguished from naturally infected birds.
Imugene is developing a range of bird flu vaccines using FAV with the ability to be able to differentiate naturally infected from Vaccinated Animals (DIVA principle). Imugene's vaccines use the patented Fowl Adenoviral Vector containing synthetic and designed generic haemagglutin (HA) and nucleoprotein (NP) genes.
Disease
Avian influenza is a viral infection that occurs in many species of birds. Wild birds worldwide carry the viruses in their intestines. The viruses are very contagious among birds including chickens, ducks, and turkeys.
Infected birds shed influenza virus in their saliva, nasal secretions and droppings. Susceptible birds become infected when they have contact with contaminated secretions or surfaces that are contaminated by infected birds. Intensively reared poultry are at very high risk if exposed to any avian influenza viruses due to the large number of birds housed closely together in commercial rearing sheds.
Infection with avian influenza viruses in poultry causes two main forms of disease distinguished by low and high extremes of virulence. The “low pathogenic” form may go undetected and usually causes only mild symptoms which may result in lower productivity and weight loss. However, the highly pathogenic form such as the outbreaks over the past few years of the influenza A (H5N1) virus – also called H5N1 virus spreads more rapidly through flocks of poultry. This form may cause disease that affects multiple internal organs and has a mortality rate of up to 90-100% within 48 hours.
The H5N1 virus can infect people. The mortality rate in humans infected with the H5N1 influenza virus strain is significant. Most of these fatal cases have occurred in people in close contact with infected poultry or contaminated surfaces.
Other types of avian influenza viruses (H7 & H9 strains) exist in several countries and outbreaks regularly occur. Imugene is developing modifications to existing proven H5N1 vaccine for these two types of avian flu.
Current treatment for poultry producers
Existing methods of dealing with birds at risk of infection are limited to culling (extermination) or individually injecting each bird with one of a few currently available vaccines.
Cull – in areas of disease outbreak (in certain countries can extend well beyond the site of infection) all birds are culled and the area is quarantined.
Vaccines – current preventative avian influenza vaccines suffer two major problems:
- Costs: Administration of vaccines by injection for each individual bird is expensive
- Safety: ‘live attenuated’ flu virus vaccines risk mutating and forming new and possibly more virulent strains of bird flu. Compounding the problem with the existing live attenuated vaccines is that during an avian influenza outbreak, diagnostic tests cannot distinguish vaccinated (uninfected) birds from those affected by the disease. However certain ‘killed’ vaccines do not risk mutation but they require larger doses and must be administered by injection
Imugene’s vector based vaccine
Imugene has developed vaccines that can be administered to broilers in ovo (into the egg) or orally in water to stimulate a bird’s immune system against the bird flu virus. The vaccines use Imugene’s proven Fowl Adenoviral Delivery Vector. This technology delivers a portion of the virus genetic material to stimulate the immune system enabling H5N1 virus infection prevention. Imugene vaccines are safe as they prevent any chance of mutations or recombination with human flu viruses.
The primary aim of commercial bird flu vaccines for broilers is to provide immunity as early as possible in a bird’s life. Immunity only needs to be short term as broiler birds typically reach market weight by 42-49 days of age.
The vaccines are inexpensive, safe, and easy to administer to entire poultry sheds without the need to inject each bird. This will enable rapid and widespread protection of commercial poultry.
Trial results
During late 2006 and 2007 Imugene conducted several poultry H5N1 challenge trials using modified versions of its trial vaccines. After the early trial successes, Imugene optimised the vaccine to deliver higher efficacy and earlier protection in subsequent trials.
Protection levels have reached 100%. This efficacy was achieved with a two-dose regime – the first dose of Imugene's vaccine injected into chicken eggs followed by an oral booster dose when the chickens were seven days old. The vaccinated chickens survived exposure to a high dose of a highly pathogenic Asian strain of the H5N1 avian influenza virus at age 21 days. All birds in this group remained completely healthy.
The results of trials to date can be summarised:
- 100% protection against highly pathogenic H5N1 with two-dose regime
- Dual method of delivery demonstrated – in ovo (egg) and orally
- Protection as early as 14-21 days of age
- Single dose also effective (>80% effective) with birds at 14 days old
- Platform suitable to make vaccines against other avian influenza viruses
- Protective across virus strains as all trials use a heterologous challenge model
- Vaccine is a marker vaccine (vaccinated birds differentiated from infected birds)
Next phase in product range development
Imugene is continuing the H5N1 product optimisation process prior to offering licenses for the global rollout in the near future. This optimisation maximises the ultimate license value for the Imugene suite of avian influenza vaccines.
The H5N1 vaccine is being supplemented with the development of a wider range of avian influenza vaccines - H7 and H9 virus vaccines. While these viruses are not as pathogenic as the H5N1 virus, they have been very damaging in commercial poultry including in the US.
Development of a matching diagnostic tool for each of the vaccines is also underway. The Imugene diagnostic test will enable vaccinated chickens to be differentiated from naturally infected chickens – a key feature if governments mandate flock vaccination. Most existing vaccines do not allow blood tests to distinguish vaccinated birds and infected birds. In a disease outbreak or during surveillance this creates confusion about which birds to cull or when the infection is gone.
Commercial proposition
An effective, easy to administer and inexpensive vaccine could be used to protect the world’s poultry industry from avian influenza outbreaks and halt the spread towards Australia, Europe and the US.
Imugene aims to produce a suite of viable avian influenza vaccines that can be used to prevent or control outbreaks in all regions of the world. The Imugene vaccines are safe, effective and can be quickly and easily administered on a large scale to broiler poultry sheds.
Major advantages of Imugene’s bird flu vaccines for broilers
- High efficacy at an early age – 14 days from hatch
- Low cost of producing commercial quantities of the vaccine
- Low cost of mass administration
- Orally or in ovo administration proven
- Individual bird handling not required
- In ovo administration via egg injection equipment undertaken by most US poultry broiler hatcheries
- Very cost effective for mass administration to entire poultry sheds containing many thousands of birds
- Marker vaccine
- Allows authorities to differentiate between infected and vaccinated birds – a vital consideration for the international poultry industry
- Safe to use
- As only a portion of the flu genetic material is used the Imugene vaccine is safe and cannot mutate or recombine with human flu viruses
- Adaptable
- Easily and quickly adapted to protect against other strains of influenza
These advantages are commercially compelling.
A summary of the most recent H5N1 trial results
Interim Avian Influenza Trial Summary - May 2007
The trials were undertaken at Benchmark Biolabs’ bio-secure clinical trial facilities in Nebraska USA.
| Group | Dose | Vaccination | Age at H5N1 Challenge | Mortality | Survival |
|---|---|---|---|---|---|
| 5 | 1 x 108 | Day 18 in ovo | 14 days | 2 of 11 | 82% |
| 7 | 1 x 106 | Day 18 in ovo | 14 days | 4 of 12 | 67% |
| Control | Nil | NA | 14 days | 5 of 8 | 37.5% |
| 6 | 1 x 108 | Day 18 in ovo Boost day 7 oral |
21 days* | 0 of 9 | 100% |
| 8 | 1 x 106 1 x 108 |
Day 18 in ovo Boost day 7 oral |
21 days* | 2 of 8 | 75% |
| Control | Nil | NA | 21 days* | 7 of 8 | 12.5% |
*Challenge dose increased
All treated groups commenced with 14 eggs however group size at challenge varied due to differences in hatching percentages and deaths occurring due to other causes (1 bird in group 8). There was no discernible difference in hatching percentages between groups receiving in ovo vaccine and other groups or control groups, suggesting the vaccine does not have a detrimental effect on hatching percentages.
The challenge virus strain was different from virus strain used to make the vaccine (heterologous challenge) to document protection across virus strains. It is normal for protection to be lower in this type of challenge model than if the challenge virus and vaccine come from the same strain of the virus (homologous challenge).