avian influenza vaccination

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  • 1. Avian Influenza VirusVaccines

2. Ideal Avian Influenza Vaccine1. Low pathogenic strain, safe to the environment.2. Able to grow well in eggs, to ensure enough antigen in thevaccine product.3. Be well matched antigenically with the prevalent viruses. 3. Limitation of Protection1. Best protection is in experimental studies with SPF chickens.2. Field protection is less than in laboratory.3. Poor quality vaccines.4. Improper storage and handling of vaccines.5. Reduced vaccine dose, or number of doses used per bird andlength of immunity is important.6. Improper vaccination technique.7. Inability to vaccinate 100% of poultry population.8. Species of birds like ducks and geese are more difficult to getgood immune response. 4. Environmental factors that impact success1. Immunological competence of birds, control of IBDV and CAV.2. Presence of maternal antibodies For broilers research supports a 2 dose regime to providethe best protection throughout the production cycle. For single dose vaccination, a full dose of vaccine at 7-10days maybe the best option at the moment.3. Virus load in environment, high environmental load mayrequire Increasing number of vaccinations. 5. Environmental factors that impact success4. HPAI breaks in vaccinated flocks may need minimum of 2doses and boost every 6 months to optimize protection.5. Changing virus (drift), periodic testing of emerging fieldagainst vaccines every 2 years. 6. Important Factors for Vaccine EfficacyVaccine quality1. HA (antigen) content in vaccine, measured byhemagglutinating activity.2. Quality of inactivation.3. Oil emulsion adjuvant.4. Vaccine stability.5. Demonstrated quality control by vaccine manufacturers. 7. INTRODUCTION 8. Introduction Current vaccines against avian influenza (AI) virus infectionsare primarily based on classical inactivated whole-viruspreparations. 9. Introduction Although administration of these vaccines can protect poultryfrom clinical disease, sterile immunity is not achieved underfield conditions, allowing for undetected virus spread andevolution under immune cover. Therefore, there is an urgent need for a robust and reliablesystem of differentiation between infected and vaccinatedanimals. 10. IntroductionAvian influenza (AI) viruses (AIV) are classified into highlypathogenic and low pathogenicity AIV, depending on the severityof disease in affected species, whereas;1. Low pathogenicity AIV (LPAIV) are ubiquitous, andrepresent part of the wild bird ecosystem, particularly inwater birds.2. Highly pathogenic AIV (HPAIV) are primarily found ascausative agents of outbreaks of fowl plague in poultry. 11. AIV OUTBREAKS 12. AIV Outbreaks Although HPAIV outbreaks have occasionally occurredworldwide, they have, until recently, been restricted ingeographic spread to the regional or, at most, national level. 13. AIV OutbreaksEndemicity of HPAIV in poultry, as observed in several countriesin Southeast Asia and Africa, as well as scattered outbreaks indomestic poultry in numerous other countries, prompted massvaccination campaigns using commercially available vaccines andalso led to increased efforts to develop novel vaccines withimproved characteristics. 14. AIV OutbreaksThe first lines of defense against AI are:1. Surveillance2. Biosecurity3. Restrictions on movement4. Rapid and reliable diagnosis5. Elimination of AI infected poultryVaccination can be an additional measure in a comprehensivecontrol strategy. 15. AVIAN INFLUENZA VACCINES 16. Avian Influenza VaccinesVaccinating poultry not only enables the protection of chickensfrom clinical signs and death following challenge with HPAIV, butalso reduces virus shedding. 17. Avian Influenza VaccinesMore importantly, it can prevent the spread of the notifiableLPAIV H5 and H7, both of which can spontaneously mutate intohighly pathogenic forms, sometimes with only a singlenucleotide alteration. 18. Avian Influenza VaccinesOwing to this potential danger, the application of live virusvaccines based on low pathogenic viruses of the H5 and H7subtype is not recommended. 19. INACTIVATEDWHOLE-VIRUS VACCINES 20. Inactivated whole-virus vaccines Historically, AIV strains used for inactivated vaccines havegenerally been based on LPAIV obtained from field outbreaks. The use of HPAIV for this purpose is limited, since thiswould require high-level biocontainment manufacturingfacilities. Virus preparations are inactivated with beta-propiolactone(EU) or formaldehyde (USA) and administered intramuscularlyin an oil emulsion mixture. 21. Inactivated whole-virus vaccinesHomologous vaccines They are prepared from virus specifying the samehaemagglutinin (HA) and neuraminidase (NA) subtype as thefield virus. The disadvantage of this is that these vaccines do not allowthe detection of infection in vaccinated flocks (DIVA:differentiation between infected and vaccinated animals). 22. Inactivated whole-virus vaccinesHeterologous vaccinesThe use of heterologous vaccines, containing the same HAsubtype as the field virus but a different NA subtype, allows aDIVA approach by differentiating NA-specific serum antibodies. 23. Inactivated whole virus H5N2 monovalentvaccinesVaccines containing Al/chicken/Mexico/232/94/CPA strain (LPAI):1. FLU-KEM vaccine (CEVA-Mexico)2. Optimune AI (Ceva-Biomune)3. Nobilis Influenza H5 (Intervet)4. Valvac AI (Boehringer) 24. ATTENUATED LIVE VACCINES 25. Attenuated live vaccinesCold-adapted attenuatedinfluenza vaccines have beendeveloped for humans andequines. 26. Attenuated live vaccines The use of attenuated live vaccines (especially of the H5 andH7 subtypes) in poultry is not recommended by the WorldOrganization for Animal Health or the Food and AgricultureOrganization of the United Nations (FAO), since they maypotentially mutate into HPAIV by reassortment or mutation ofthe HA cleavage site. Moreover, like most inactivated vaccines, these live vaccinesdo not support an easy DIVA strategy. 27. Attenuated live vaccinesSince the advent of reverse genetics for influenza virus and thedevelopment of entirely plasmid-based reverse genetic systemsto rescue recombinant influenza virus, without the need forhelper virus, the timely generation of recombinant influenzaviruses, according to the respective epidemiological situation,has now become possible 28. Attenuated live vaccinesThe use of plasmid-based reverse genetics allows the safe andefficient generation of attenuated high-growth reassortantviruses, which derive the genes encoding the envelope proteinsHA and/or NA from circulating influenza A viruses and theinternal genes from vaccine donor strains, such as influenza APuerto Rico/8/34 (PR8) (H1N1) or A/WSN 33 (H1N1). 29. Attenuated live vaccinesTo avoid the requirement for high-level biocontainment facilities,and to obtain high virus yields in ECE, the polybasic cleavage siteof HPAIV H5 has been altered by deletion and/or mutation ofbasic amino acids, resulting in proteins specifying a monobasiccleavage site characteristic for LPAIV. 30. Attenuated live vaccines The resulting viruses were used as inactivated oil emulsion AIvaccines to immunize chickens, ducks and geese. They provided effective protection from clinical disease and asignificant reduction of virus shedding after challenge. 31. VECTOR VACCINES 32. Vector vaccines Influenza viruses possess a limited number of immunogenicproteins, including the envelope glycoproteins HA and NA,matrix proteins M1 and M2, nucleoprotein NP and non-structuralprotein NS1. Of these, HA has been demonstrated to be the most relevantfor inducing neutralizing antibodies. 33. Vector vaccines Different chicken viruses have been used as vectors for theexpression of AIV proteins. They include attenuated strains of DNA viruses, such as fowlpox (FP) virus and infectious laryngotracheitis (ILT) virus, aswell as RNA viruses, such as NDV. 34. REPLICATION-COMPETENTVECTOR VACCINES 35. POXVIRUSES 36. Poxviruses Attenuated but replication-competent viruses are probablythe most economic vaccines, since they combine theimmunogenic properties of protein and DNA vaccines and,due to their proliferation in the immunized animal, areefficacious even at low doses. 37. Poxviruses Over the last few decades, many virus genomes have becomeaccessible to reverse genetics and DNA manipulationtechnology, and directed deletion of virulence genes, as wellas insertion of foreign genes, has become feasible. 38. Poxviruses Poxviruses were among the first viral vectors used for theexpression of heterologous proteins. Avian influenza virus genes were inserted into the genomes ofattenuated FP virus (FPV), which were already in use as live-virusvaccines against FP in chickens and turkeys. 39. Poxviruses Non-essential regions of the FPV genome, such as thethymidine kinase gene locus, were used as insertion sites andthe foreign proteins were expressed under the control ofstrong poxvirus promoters, for instance, the vaccinia virus H6promoter. The considerable size of the FPV genome, of nearly 300kilobase pairs, allowed not only insertions of single genes butalso the simultaneous insertion of several genes, encoding,for example, HA and NA, or HA and NP. 40. Poxviruses Single vaccinations with approximately 10 log 5 infectiousunits of H5 or H7 expressing FPV recombinants protectedchickens and ducks against lethal challenge infections withhomologous or heterologous AIV of the correspondingsubtypes. However, like other AIV vaccines, HA-expressing FPV did notconfer sterile immunity, as demonstrated by the re-isolationof HPAIV challenge virus from tracheal and cloacal swabs. 41. Poxviruses Avian influenza virus vaccines based on fowl pox can beproduced economically on the chorioallantois membrane ofchicken embryos or in primary chicken cell cultures, and canbe administered to one-day-old chickens. However, to obtain optimal protection, individualsubcutaneous vaccination (the wi