Notifiable Avian Influenza
Hazard Specific Plan

Appendix N: Overview of Avian Influenza Vaccines

Based on the information available concerning the control and use of vaccines against AI, the main advantages and disadvantages that can be expected regarding the use of vaccination for NAI prevention and control are summarized below:

• Advantages
  • Vaccination reduces clinical signs, including mortality and associated losses;
  • It reduces the risk of virus infection to individual birds, and, therefore, the risk of disease introduction into a vaccinated farm; and
  • It reduces the amount of virus that is shed in the environment by an infected bird. Thus, if the virus enters a vaccinated farm there is less risk that the virus will spread to other farms.
    
• Disadvantages
  • The administration of a vaccination is difficult and expensive, requiring intensive organization (e.g., at the present time, the only vaccines available that induce protective immunity must be administered by individual injection one to three times);
  • In certain species, such as ducks, geese, and turkeys, the immune response induced by vaccination is not well known;
  • Vaccination may mask the occurrence of disease on a farm and delay its detection;
  • If a vaccination is not properly administered and surveillance is not properly conducted, the disease may eventually become persistent as the virus could continue to circulate among birds that are not fully immune, which may lead to an LPNAI virus mutating to a highly pathogenic form;
  • Vaccination may induce a false sense of security and thereby favour the relaxation of biosecurity and surveillance by the owner; and
  • Vaccination may induce countries to apply trade restrictions.

Vaccination Against Avian Influenza in Canada

There is no vaccination against NAI allowed in Canada at the present time; however, limited use permits were issued for an inactivated H3N4 vaccine for use in turkey breeder flocks in 2005 by the CFIA's VBS. The purpose of vaccinating these flocks with an inactivated H3N4 vaccine was to mitigate the clinical picture of H3N2 infection. All of the veterinarians applied to use the vaccine on behalf of companies with turkey breeder flocks located near a swine farm that had experienced problems with H3N2 swine influenza.

The decisions to issue limited-use permits were made on a case-by-case basis. Each permit was for shipments of vaccine to be used in turkey breeder flocks, all of which had experienced clinical signs, mainly a drop in egg production due to the presence of H3 virus. Only four companies in Canada applied for the import permit in 2005. As of June 2006, three of these companies continued to use the vaccine as a disease-control tool concurrently with enhanced biosecurity measures.

Worldwide Vaccination Against Avian Influenza

There is limited precise information available on the use of vaccination against NAI on poultry, especially against the Asian strain of HPAI H5N1. Although the answers to many questions are not yet available, the experience gained by some countries using vaccination against NAI , and the willingness of international animal health organizations to recognise vaccination, leads the international veterinary community to seriously consider vaccination as a valuable disease-control method.

The quantity of AI vaccine used around the world in poultry is not well documented, but reliable information suggests that the largest single use was more than two billion doses of inactivated H5N2 AI vaccine in China (December 2003 to present day). The following countries have also used AI vaccines:

• Indonesia uses H5 inactivated vaccine;
• Pakistan began using H7 inactivated vaccine in 1995 in three regions following outbreaks of H7N3 HPAI (1995, 2001, and 2004);
• In Mexico, an AI vaccination program was implemented in January 1995 with over 1.3 billion doses of inactivated vaccines and 850 million doses of recombinant fowl pox used. Although H5N2 HPAI was eradicated in 1995, H5N2 LPAI continues to circulate in central Mexico.

In contrast with LPAI, H9N2 inactivated vaccines have been and continue to be used in many countries within Asia, the Middle East, and Eastern Europe, although the number of doses is unknown. Vaccines for the control of LPAI have been used sporadically. In northern Italy, H7 inactivated vaccine has been used to control LPAI since 2001. Recently, H7 inactivated vaccine was successfully used in the US to control LPAI in a commercial table egg layer operation.

Notifiable Avian Influenza Vaccine Availability in Canada

Only killed vaccines of AI virus, or biotechnology-derived vaccines containing the HA are considered suitable for use in poultry as part of an AI control program. The ability of the virus to mutate or to recombine with related influenza viruses makes live vaccines of H5 and H7 serotypes unacceptable for use at the present time. The vaccines currently available require the injection of vaccine into individual birds (i.e., intramuscular or subcutaneous), rather than the less costly oral or spray administration that is available for other live avian vaccines.

Note: While the following information is considered current at the time of writing, it is subject to change as additional studies and new products become available. Future advances in biotechnology-derived vectored vaccines may include products with other more automated routes of administration, such as in ovo, water, or spray administration.

AI inactivated virus vaccines licensed in Europe have been used in a recent eradication program in Italy through the Differentiating Infected from Vaccinated Animals (DIVA) Strategy. This strategy requires that the master seed virus used in the vaccine be different than the outbreak strain, so most companies marketing AI vaccines have at least two different N types of H5 and H7 strains available. Tests for antibodies to the N proteins can be used to differentiate poultry flocks exposed to outbreak virus from vaccinated poultry flocks, and are especially important as AI vaccines cannot immediately protect vaccinated birds exposed to an outbreak strain. This strategy would also be available for any biotechnology-derived vaccine which lacks the NA. At this time, NC-FAD does not have the capacity to perform NI testing in an outbreak situation.

Killed NAI Vaccines

AI vaccines against H5 and H7 subtypes have been licensed or conditionally licensed in the US and could be made available in Canada. The United States Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS) has a vaccine bank contract for killed AI vaccines, including two strains of H5 and two strains of H7 AI virus, which may also be available for use in Canada, with the permission of the USDA-APHIS.

Efficacy-These vaccines are able to protect chickens from disease and death from HPAI virus if challenged two or more weeks after vaccination. There is a concern that the widespread use of these vaccines may mask the clinical signs of HPAI, and allow the replication and shedding of the outbreak virus during the first week or two after vaccination. The use of surveillance strategies (e.g., monitoring cloacal swabs for influenza virus antigens) rather than just monitoring clinical signs in poultry flocks at risk would reduce the significance of this concern. Some initial data has been generated to show that vaccinated chickens challenged two or more weeks after vaccination may not shed sufficient virus to infect unvaccinated birds, and this reduction of shedding may reduce the risk of human disease from exposure to poultry infected with some serotypes of virus.

Label-The label on a currently available USDA-APHIS conditionally licensed killed AI vaccine has the following instructions, which are probably present on similar products: "Inject 0.5 ml subcutaneously, using aseptic technique, per chicken. Vaccinate at four weeks of age; revaccinate four to six weeks later."

Withdrawal time-The label also includes the statement, "Warning: Do not vaccinate within 42 days before slaughter." This withdrawal time is based on the local reaction to the oil-based adjuvant generally found in this type of product, and could be reduced in Canada if data was provided to show that no residues affecting food safety are present in the vaccinated chickens. Europe's licensing of similar vaccines has no withdrawal time requirement.

Other poultry species-Some efficacy data is being generated in other poultry species, such as ducks and turkeys, with these products in Europe. Preliminary data suggests that ducks may require twice the dose required for chickens, and protective antibody titres may initially appear five weeks after vaccination. Challenge protection data in species other than chickens are not yet generally available, but trials looking at duck and turkey protection are apparently in progress in Europe. Preventive vaccination to protect poultry with access to migrating wild birds has been recently used in several countries.

Biotechnology-derived Vaccines

The USDA-APHIS licensed AI fowlpox vaccine, live fowlpox virus vector, and H5 subtype (Merial) could be available for use in Canada.

Efficacy-The manufacturer has shown protection against highly pathogenic H5 challenge between four and 20 weeks after vaccination. The expected time of the onset of protective immunity is not clear from the data presented, and may be less than four weeks. Some independently generated data showed that vaccine efficacy may be reduced in birds already immune to fowl pox, but this would not be a problem in day-old birds.

Label-This vaccine is recommended for inoculation of chickens at one day of age or older by subcutaneous injection of 0.2 ml.

Withdrawal time-The vaccine has a withdrawal time of 21 days before slaughter, which is the minimum regulated withdrawal time for all vaccines in the US. Again, this withdrawal time could be reduced in Canada if data was provided to show that no residues affecting food safety are present in the vaccinated chickens.

Other poultry species-Current labelling indicates use in chickens only and currently there do not appear to be any studies to demonstrate protection in any other poultry species.

As part of preparedness efforts and in consideration of the fact that there is no authorized NAI vaccine available in Canada, the CFIA is in the process of accessing different sources of NAI vaccines should vaccination be accepted for a control program.

OIE Standards and Trade Implications

According to the OIE's Terrestrial Animal Health Code, preventive or emergency vaccination against NAI should not affect the timing of re-entry into international commerce following an outbreak; however, individual countries may decide otherwise. Prolonged trade restriction may be imposed when an NAI vaccination program does not enable the application of a DIVA strategy either because of the type of vaccine used or because the monitoring program does not guarantee that the virus is no longer circulating. On the other hand, trade restrictions may be lifted if it is possible to demonstrate that the virus is not circulating in the vaccinated poultry population.

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