What can we expect from Avian Influenza vaccines?
In a country or a territory heavily affected by Avian Influenza (AIAvian Influenza), poultry vaccination is primarily a tool to prevent clinical and economical losses due infection with AIVAvian Influenza Virus. It is also a complement to sanitary and biosecurity practices to achieve eradication of the disease and recover the AI-free status. If it is used as the sole means to combat the disease, vaccination cannot lead to eradication. This is why vaccination against AI needs to be organized, coordinated and accompanied by disease monitoring and eradication plans.
In a country free of AI, vaccination can also be used to lower the risk of being hit and slow down the spread of the virus once a farm is infected.
- What are the specifications for a good Avian Influenza vaccine?
When it comes to efficacy, an AI vaccine must answer the following 5 pre-requisites:
- The capacity to remain efficacious despite frequent antigenic variations of the challenging virus (see more)
- The capacity to overcome MDAMaternally Derived Antibodies: antibodies produced by the breeders and transmitted to their progeny through the egg yolk. that are present in the young chicken when the breeders are vaccinated (or exposed to the virus). (see more)
- The possibility that it can be used at the hatchery where the conditions are right to achieve maximum vaccine coverage. (see more)
- The need for a long lasting immunity so that revaccinations are unnecessary. (see more)
- The ability to keep monitor the spread of the challenge virus following vaccination so that an eradication plan can be followed. (see more)
Antigenic variability of the challenge virus greatly affects the efficacy of classical inactivated vaccines (including those derived from reverse-genetics) and possibly the recombinant vector vaccines of the Fowl Pox (rFP-HAHemagglutinin)or Newcastle Disease (rNDV-HA) types.
Classical inactivated vaccines induce an immunity that is mostly, if not exclusively, composed of antibodies. For this reason, antibody response must be strong and specific, and this can only be achieved if the vaccine is manufactured with a high antigenic mass and regularly updated to take account of the evolution of the field virus. In theory, this is should be possible when the Reverse Genetics technique is used.
But in the real life, it is just impossible to predict when the field virus will mutate, and in the end, which virus will challenge the farm, i.e. which vaccine strain should be used. The vaccine update can only be made after vaccination failures are observed and the necessary reverse genetic antigen is applied. Even so, this does not meet the needs of territories where field strains of various antigenic profiles are present. The use of multivalent killed vaccines or multiple vaccinations using different killed vaccines is simply not realistic.
The vector rHVT-HA5 vaccine has demonstrated its capacity to remain effective even if very significant changes in the field virus occur, as long as the virus is of the H5 subtype (which is the case in the US).
Interference with MDA occurs very soon after vaccination. Breeders are the most valuable animals in the poultry chain, and are generally first to be vaccinated. Soon after, they carry antibodies that are transmitted to their progeny, the MDA. Interference between classical killed AI vaccines and MDA has been well documented. The only way to overcome MDA is to delay vaccination and wait until the MDA have waned. Thus an optimal time for vaccination is difficult to determine for a given flock, and carries the risk of an early field infection. Furthermore, MDA prevent the administration of the vaccine at the hatchery, which is necessary to achieve optimal coverage. Interference between MDA and vaccine has also been shown for the vector Fowl Pox (rFP-HA) and Newcastle Disease (rNDV-HA) types of recombinant vector AI vaccine. For the rFP-HA vaccine, the dominant interference is related to expression of the HA insert; the Fowl Pox virus is able to replicate even in the presence of anti-Pox MDA. For the rNDV-HA vaccine, the interference is more closely related to the NDVNewcastle Disease Virus vector itself, which is well known for vaccination against the Newcastle Disease ( #5 ). Early vaccination against ND with a live ND vaccine both reduces and shortens the immunity.
Interference of MDA when using the vector rHVT-HA5 vaccine is not a major issue. Many years of use of HVTHerpes Virus of Turkey vaccine to prevent the Marek’s disease have established its capacity to replicate in the presence of MDA against the vector. Besides, many experiments have demonstrated the absence of significant interference of MDA directed against AIV on the take of this vaccine ( #8 , #14 , #15 , #22 , #23 ).
Administration of the vaccine at the hatchery is critical and cannot be avoided. It is the only way to ensure good vaccine coverage, so that, in case of challenge, the fewest birds are susceptible. Because of interference with MDA, and the difficulties of administering a large (0.5 ml) dose by the subcutaneous route, killed vaccines are unsuitable for hatchery vaccination, especially when the vaccines are not concentrated. This applied particularly in-ovo vaccination is the only available route of administration.
Similarly, because of interference with MDA, recombinant vector AI vaccines of the rFP-HA or rNDV-HA types cannot reliably be used in the hatchery.
Because of its nature and its capacity to escape interference with MDA, the rHVT-HA5 vaccine is highly suitable as a hatchery vaccine and is presented in a way familiar to users in the US.
The capability of the vaccine to induce a long lasting immunity is critical. In countries where the disease is endemic and where vaccination with killed AI vaccine is used - for example, in China - long living birds like layers or breeders are vaccinated up to 6 times to ensure an acceptable level of protection. This is costly, impractical and shows the limitations of killed vaccines. As of today, no alternative is available when classical killed vaccines are used.
We have described how experience with the vector rHVT-HA5 vaccine has shown that much longer lasting immunity can be achieved, but this needs to be further investigated, either using the vector rHVT-HA5 vaccine alone or in combination with killed vaccine in the same vaccination program.
The possibility to monitor the spreading of the field HPAIV in vaccinated flocks is usually named the DIVA strategy i.e. the possibility to Differentiate Infected from Vaccinated Animals. Killed vaccines are made from whole inactivated AIV so that antibody response to infection cannot be differentiated from antibody response to vaccination, especially when a vaccine homologous to the field virus is used. This is why “vaccination against AI” is often criticized for masking the infection.
The vector rHVT-HA5 vaccine does not contain the whole AIV, and for this reason, it induces antibodies only against the HA insert, and not against the nucleoprotein or the neuraminidase that are other components of the virus. As a result, antibody response to vaccination can be detected using the HI test. If vaccinated birds are infected then the field virus will replicate (although to a much lower degree), and some antibody response to the nucleoprotein or the M2 protein will be detected (see our sources #6 , #16 , #24 ).
This will need further investigation but in the short term, infection could also easily be detected by PCR so that a real DIVA strategy can be applied with this vaccine. Vaccination with the vector rHVT-HA5 vaccine does not prevent the monitoring of the spread of the field virus and can help ensuring the AI-free status of flocks or territories. This is a strong argument to support the maintenance of exports in the presence of vaccination.