A view and an overview on the control of avian influenza outbreaks in poultry: (2-6) The role of vaccines

Historical background

So far, the use of mass vaccination as an option for the control of avian influenza (AI) in poultry was not applied in the field until1995. During the outbreak of HPAI H5N2 in 1994-1995, Mexico applied large-scale vaccination campaign using inactivated homologous H5N2 vaccines [18, 31]. Also, Pakistan used inactivated H7N1 vaccines to control HPAI H7N1 outbreaks in 1995 [37-39]. Thereafter the use of vaccines as emergency, prophylactic or routine strategy was frequently reported to control H5, H7 and H9 viruses. The inactivated H7N3 and H7N1 vaccines as a part of the intervention plan were used in Italy against H7N1 and H7N3 in 2000-2002, respectively [9], in Pakistan against H7N1 in 2003-2004 [39], in USA against LPAIV H7N2 in 2003 [8], and in Korea against H7N7 in 2005 [55]. Recently, inactivated H7N3 vaccines were used in Mexico to control the ongoing outbreaks of HPAI H7N3 since 2012 [25]. After the re-emergence of the Asian H5N1 in 2003, vaccines were used in many countries to mitigate the economic and social impact of the disease which was reviewed comprehensively by Dr. David Swayne [55]. Currently, four countries use different H5N1 vaccines in poultry: China since 2004, Indonesia since 2004, Vietnam since 2005 and Egypt since 2006 [55]. Occasionally, vaccines for HPAI H5N1 have been used for short periods in Cote d’Ivoire, France, Kazakhstan, Mongolia, Netherlands, Pakistan, Russia and Sudan [55]. Furthermore, more than 10 countries used inactivated H9N2 vaccines in poultry like China since 1998 [33], Korea since 2007 [30], Israel since 2003 [13] and Egypt since 2012-2013. Canada and USA used vaccines to control H1 and H3 swine influenza viruses in turkeys. Germany, South Africa and USA used vaccines to control H6 outbreaks and also USA used H2 and H4 vaccines [55]. The use of bivalent H5-H7 and H7-H9 inactivated vaccines were used in Italy [8] and Pakistan [9], respectively.

Types of vaccines

Inactivated whole virus vaccines

The conventional inactivated whole virus vaccines are the currently the most used vaccines in poultry and it was expected to continue for the next 10 years [48, 55]. Generation of inactivated vaccines requires propagation of the virus in embryonated chicken eggs (ECE) to high yield followed by inactivation of the virus by using for example betapropiolactone or formalin. It is worth to mention that in case of HPAIV, for safety reasons propagation of the virus must be conducted in high containment facilities (biosafety level – 3). However, using recent molecular techniques (i.e. reverse genetics) modification of the viral genome can be successfully achieved to decrease virulence of the virus and/or increase replication titer in ECE.

Recombinant viral-vectored vaccines

Some viruses can stably express a foreign gene(s) without hindering their replication in the host. Since the last two decades, there is an increased interest in the insertion of the HA and rarely NA of AIV in other viruses to obtain live bivalent (or multivalent) vaccines. Development of recombinant fowl pox virus (rFPV), Newcastle disease virus (rNDV), herpes virus of turkeys (rHVT), infectious laryngotracheitis virus (ILT), adenovirus or baculovirus have been frequently described [3, 9]. So far, only H5-expressing viral vectored vaccines have been used in the field to control HPAI H5N1 and H5N2 outbreaks in poultry (e.g.: in China, Egypt and Mexico) [6, 55].

Advantages of vaccines

The major advantages of the vaccine to control AIV in poultry are:

decrease the amount of excreted virus.
reduce or prevent morbidity and mortality.
stop bird-to-bird transmission.
limit decrease in egg production.
viral-vectored vaccines, can be applied by mass vaccination (e.g. spray, drinking water, etc.) to protect birds simultaneously against several poultry viral pathogens.
as a form of live vaccines, the recombinant vaccines elicit not only humoral but also mucosal and cellular immune responses.
the generation of recombinant or genetically-modified vaccines can overcome the availability of antigenic match between circulating and vaccine strains as well as providing a tool to differentiate between natural infected and vaccinated animals "DIVA" (for more information please refer to [3, 48, 50, 54, 55].
Protection of valuable birds or zoo birds can be achieved if the vaccine given before the epidemic

Disadvantages of vaccines

Nevertheless, there are several challenges facing the efficiency of the vaccine to control AIV outbreaks in poultry, for example:

Vaccine is HA subtype specific and in some regions where multiple subtypes are co-circulating (i.e., H5, H7 and H9), vaccination against multiple HA subtypes is required [49].
Vaccine-induced antibodies hinder routine serological surveillance and differentiation of infected birds from vaccinated ones requires more advanced diagnostic strategies [50].
Vaccination may prevent the clinical disease but can’t prevent the infection of vaccinated birds, thus continuous “silent” circulation of the virus in vaccinated birds poses a potential risk of virus spread among poultry flocks and spillover to humans [10, 20, 40, 47].
Formalin levels in the inactivated vaccines may reduce egg production in layer hens [36]
Immune pressure induced by vaccination on the circulating virus increases the mutations rate of the virus (evolution) and accelerates the viral antigenic drift to evade the host-immune response [5, 11, 12, 15, 30-32, 42].
After emergence of antigenic variants, the vaccine becomes useless and/or inefficient to protect the birds and periodical update of the vaccine is required [1, 19, 26, 31, 44].
Vaccine-induced immunity (i.e. inactivated vaccines) usually peaks three to four weeks after vaccination and duration of protection following immunization is not well studied yet [52].
Maternally acquired immunity induced by vaccination of breeder flocks could interfere with vaccination of young birds [2, 14, 27, 34, 46]. To overcome the influence of maternal immunity it was recommended to:

use heterologous prime-boost strategy: e.g. vaccinate birds with recombinant vaccine at 1-3 days of life then another inactivated (or different recombinant) vaccine after 2 – 3 weeks

vaccinate birds with a vaccine different from their breeders

vaccinate birds later (e.g. at 10 – 14 day-old) when their maternal immunity wane

recombinant adenovirus and rHVT vaccines provided good immunity against challenge with HPAIV H5N1 under laboratory conditions in presence of maternal immunity

Other domestic poultry (i.e., ducks, geese, turkeys), zoo and/or exotic birds even within the same species (i.e., Muscovy vs. Pekin ducks) respond differently to vaccination which have not yet been fully investigated compared to chickens [4, 7, 24, 28, 29, 41, 43, 56]. For example: ducks and geese require higher doses and may be multiple vaccination (≥ 3 times).
Like other vaccines in poultry, immune response of AIV-vaccinated birds can be inhibited due to concomitant or prior infection with immunosuppressive pathogens (Gumboro virus, chicken anemia virus, etc.) or ingestion of mycotoxins which are common in poultry operations [21, 22, 45, 51].
For the recombinant vaccines, keeping cold-chain is pivotal
Recombinant vaccines (e.g. recombinant NDV-H5 vaccines) may aggravate respiratory tract infections especially if co-infection with bacteria (e.g. E.coli) exists
Although difficult, reassortment with wild type viruses can not be totally neglected
Although rare, however contamination of live virus vaccines by for example, but not limited to, chicken anemia virus [35], avian reticuloendotheliosis virus [16, 57], avian leukosis virus [17] or avian paramyxoviruses [23] has been reported.
Last but not least, factors related to vaccine manufacturing, quality, identity of vaccine strain, improper handling and/or administration can be decisive for efficiency of any AIV vaccine [52, 53].

Although vaccines are beneficial to mitigate the impact of HPAI outbreaks in poultry, we still need new alternative and/or complementary strategies target different AIV serotypes/subtypes/drift-variants. In the following articles we will throw the light on other possible approaches for control of AIV in poultry.

References

Abdelwhab EM, Grund C, Aly MM, Beer M, Harder TC, Hafez HM (2011) Multiple dose vaccination with heterologous H5N2 vaccine: immune response and protection against variant clade 2.2.1 highly pathogenic avian influenza H5N1 in broiler breeder chickens. Vaccine 29:6219-6225
Abdelwhab EM, Grund C, Aly MM, Beer M, Harder TC, Hafez HM (2012) Influence of maternal immunity on vaccine efficacy and susceptibility of one day old chicks against Egyptian highly pathogenic avian influenza H5N1. Veterinary microbiology 155:13-20
Abdelwhab EM, Veits J, Mettenleiter TC (2014) Prevalence and control of H7 avian influenza viruses in birds and humans. Epidemiol Infect:1-25
Bertelsen MF, Klausen J, Holm E, Grondahl C, Jorgensen PH (2007) Serological response to vaccination against avian influenza in zoo-birds using an inactivated H5N9 vaccine. Vaccine 25:4345-4349
Boni MF (2008) Vaccination and antigenic drift in influenza. Vaccine 26 Suppl 3:C8-14
Bublot M, Pritchard N, Cruz JS, Mickle TR, Selleck P, Swayne DE (2007) Efficacy of a fowlpox-vectored avian influenza H5 vaccine against Asian H5N1 highly pathogenic avian influenza virus challenge. Avian diseases 51:498-500
Cagle C, To TL, Nguyen T, Wasilenko J, Adams SC, Cardona CJ, Spackman E, Suarez DL, Pantin-Jackwood MJ (2011) Pekin and Muscovy ducks respond differently to vaccination with a H5N1 highly pathogenic avian influenza (HPAI) commercial inactivated vaccine. Vaccine 29:6549-6557
Capua I, Alexander DJ (2004) Avian influenza: recent developments. Avian Pathology 33:393-404
Capua I, Marangon S (2007) The use of vaccination to combat multiple introductions of Notifiable Avian Influenza viruses of the H5 and H7 subtypes between 2000 and 2006 in Italy. Vaccine 25:4987-4995
Capua I, Alexander DJ (2008) Ecology, epidemiology and human health implications of avian influenza viruses: why do we need to share genetic data? Zoonoses and public health 55:2-15
Cattoli G, Fusaro A, Monne I, Coven F, Joannis T, El-Hamid HS, Hussein AA, Cornelius C, Amarin NM, Mancin M, Holmes EC, Capua I (2011) Evidence for differing evolutionary dynamics of A/H5N1 viruses among countries applying or not applying avian influenza vaccination in poultry. Vaccine 29:9368-9375
Cattoli G, Milani A, Temperton N, Zecchin B, Buratin A, Molesti E, Aly MM, Arafa A, Capua I (2011) Antigenic drift in H5N1 avian influenza virus in poultry is driven by mutations in major antigenic sites of the hemagglutinin molecule analogous to those for human influenza virus. J Virol 85:8718-8724
Davidson I, Fusaro A, Heidari A, Monne I, Cattoli G (2014) Molecular evolution of H9N2 avian influenza viruses in Israel. Virus genes 48:457-463
De Vriese J, Steensels M, Palya V, Gardin Y, Dorsey KM, Lambrecht B, Van Borm S, van den Berg T (2010) Passive protection afforded by maternally-derived antibodies in chickens and the antibodies' interference with the protection elicited by avian influenza-inactivated vaccines in progeny. Avian diseases 54:246-252
Escorcia M, Vazquez L, Mendez ST, Rodriguez-Ropon A, Lucio E, Nava GM (2008) Avian influenza: genetic evolution under vaccination pressure. Virology journal 5:15
Fadly A, Garcia MC (2006) Detection of reticuloendotheliosis virus in live virus vaccines of poultry. Developments in biologicals 126:301-305; discussion 327
Fadly A, Silva R, Hunt H, Pandiri A, Davis C (2006) Isolation and characterization of an adventitious avian leukosis virus isolated from commercial Marek's disease vaccines. Avian diseases 50:380-385
Garcia A, Johnson H, Srivastava DK, Jayawardene DA, Wehr DR, Webster RG (1998) Efficacy of inactivated H5N2 influenza vaccines against lethal A/Chicken/Queretaro/19/95 infection. Avian diseases 42:248-256
Grund C, Abdelwhab el SM, Arafa AS, Ziller M, Hassan MK, Aly MM, Hafez HM, Harder TC, Beer M (2011) Highly pathogenic avian influenza virus H5N1 from Egypt escapes vaccine-induced immunity but confers clinical protection against a heterologous clade 2.2.1 Egyptian isolate. Vaccine 29:5567-5573
Hafez MH, Arafa A, Abdelwhab EM, Selim A, Khoulosy SG, Hassan MK, Aly MM (2010) Avian influenza H5N1 virus infections in vaccinated commercial and backyard poultry in Egypt. Poult Sci 89:1609-1613
Hao YX, Yang JM, He C, Liu Q, McAllister TA (2008) Reduced serologic response to avian influenza vaccine in specific-pathogen-free chicks inoculated with Cryptosporidium baileyi. Avian diseases 52:690-693
Hegazy AM, Abdallah FM, Abd-El Samie LK, Nazim AA (2011) The relation between some immunosuppressive agents and widespread nature of highly pathogenic avian influenza (HPAI) post vaccination. Journal of American Science 7:66-72
Jorgensen PH, Handberg KJ, Ahrens P, Manvell RJ, Frost KM, Alexander DJ (2000) Similarity of avian paramyxovirus serotype 1 isolates of low virulence for chickens obtained from contaminated poultry vaccines and from poultry flocks. The Veterinary record 146:665-668
Kapczynski DR, Swayne DE (2009) Influenza vaccines for avian species. Current topics in microbiology and immunology 333:133-152
Kapczynski DR, Pantin-Jackwood M, Guzman SG, Ricardez Y, Spackman E, Bertran K, Suarez DL, Swayne DE (2013) Characterization of the 2012 highly pathogenic avian influenza H7N3 virus isolated from poultry in an outbreak in Mexico: pathobiology and vaccine protection. Journal of virology 87:9086-9096
Kilany WH, Abdelwhab EM, Arafa AS, Selim A, Safwat M, Nawar AA, Erfan AM, Hassan MK, Aly MM, Hafez HM (2011) Protective efficacy of H5 inactivated vaccines in meat turkey poults after challenge with Egyptian variant highly pathogenic avian influenza H5N1 virus. Veterinary microbiology 150:28-34
Kim JK, Kayali G, Walker D, Forrest HL, Ellebedy AH, Griffin YS, Rubrum A, Bahgat MM, Kutkat MA, Ali MA, Aldridge JR, Negovetich NJ, Krauss S, Webby RJ, Webster RG (2010) Puzzling inefficiency of H5N1 influenza vaccines in Egyptian poultry. Proceedings of the National Academy of Sciences of the United States of America 107:11044-11049
Koch G, Steensels M, van den Berg T (2009) Vaccination of birds other than chickens and turkeys against avian influenza. Revue Scientifique et Technique, Office International des Epizooties 28:307-318
Lecu A, De Langhe C, Petit T, Bernard F, Swam H (2009) Serologic response and safety to vaccination against avian influenza using inactivated H5N2 vaccine in zoo birds. Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians 40:731-743
Lee CH, Byun SH, Lee YJ, Mo IP (2012) Genetic evolution of the H9N2 avian influenza virus in Korean poultry farms. Virus genes 45:38-47
Lee CW, Senne DA, Suarez DL (2004) Effect of vaccine use in the evolution of Mexican lineage H5N2 avian influenza virus. Journal of virology 78:8372-8381
Lee DH, Song CS (2013) H9N2 avian influenza virus in Korea: evolution and vaccination. Clinical and experimental vaccine research 2:26-33
Li C, Yu K, Tian G, Yu D, Liu L, Jing B, Ping J, Chen H (2005) Evolution of H9N2 influenza viruses from domestic poultry in Mainland China. Virology 340:70-83
Maas R, Rosema S, van Zoelen D, Venema S (2011) Maternal immunity against avian influenza H5N1 in chickens: limited protection and interference with vaccine efficacy. Avian Pathology 40:87-92
Marin SY, Barrios PR, Rios RL, Resende M, Resende JS, Santos BM, Martinsa NR (2013) Molecular characterization of contaminating infectious anemia virus of chickens in live commercial vaccines produced in the 1990s. Avian diseases 57:15-21
Meng D, Hui Z, Yang J, Yuan J, Ling Y, He C (2009) Reduced egg production in hens associated with avian influenza vaccines and formalin levels. Avian diseases 53:16-20
Naeem K, Hussain M (1995) An outbreak of avian influenza in poultry in Pakistan. The Veterinary record 137:439
Naeem K, Ullah A, Manvell RJ, Alexander DJ (1999) Avian influenza A subtype H9N2 in poultry in Pakistan. The Veterinary record 145:560
Naeem K, Siddique N (2006) Use of strategic vaccination for the control of avian influenza in Pakistan. Developments in biologicals 124:145-150
Naeem K, Siddique N, Ayaz M, Jalalee MA (2007) Avian influenza in Pakistan: outbreaks of low- and high-pathogenicity avian influenza in Pakistan during 2003-2006. Avian diseases 51:189-193
Oh S, Martelli P, Hock OS, Luz S, Furley C, Chiek EJ, Wee LC, Keun NM (2005) Field study on the use of inactivated H5N2 vaccine in avian species. The Veterinary record 157:299-300
Park KJ, Kwon HI, Song MS, Pascua PN, Baek YH, Lee JH, Jang HL, Lim JY, Mo IP, Moon HJ, Kim CJ, Choi YK (2011) Rapid evolution of low-pathogenic H9N2 avian influenza viruses following poultry vaccination programmes. The Journal of general virology 92:36-50
Philippa JD, Munster VJ, Bolhuis H, Bestebroer TM, Schaftenaar W, Beyer WE, Fouchier RA, Kuiken T, Osterhaus AD (2005) Highly pathogenic avian influenza (H7N7): vaccination of zoo birds and transmission to non-poultry species. Vaccine 23:5743-5750
Rauw F, Palya V, Van Borm S, Welby S, Tatar-Kis T, Gardin Y, Dorsey KM, Aly MM, Hassan MK, Soliman MA, Lambrecht B, van den Berg T (2011) Further evidence of antigenic drift and protective efficacy afforded by a recombinant HVT-H5 vaccine against challenge with two antigenically divergent Egyptian clade 2.2.1 HPAI H5N1 strains. Vaccine 29:2590-2600
Robinson JH, Easterday BC (1979) Avian influenza virus infection of the immunosuppressed turkey. American journal of veterinary research 40:1219-1222
Sarfati-Mizrahi D, Lozano-Dubernard B, Soto-Priante E, Castro-Peralta F, Flores-Castro R, Loza-Rubio E, Gay-Gutierrez M (2010) Protective dose of a recombinant Newcastle disease LaSota-avian influenza virus H5 vaccine against H5N2 highly pathogenic avian influenza virus and velogenic viscerotropic Newcastle disease virus in broilers with high maternal antibody levels. Avian diseases 54:239-241
Savill NJ, St Rose SG, Keeling MJ, Woolhouse ME (2006) Silent spread of H5N1 in vaccinated poultry. Nature 442:757
Spackman E, Swayne DE (2013) Vaccination of gallinaceous poultry for H5N1 highly pathogenic avian influenza: current questions and new technology. Virus research 178:121-132
Suarez DL, Schultz-Cherry S (2000) Immunology of avian influenza virus: a review. Developmental and comparative immunology 24:269-283
Suarez DL (2005) Overview of avian influenza DIVA test strategies. Biologicals : journal of the International Association of Biological Standardization 33:221-226
Sun S, Cui Z, Wang J, Wang Z (2009) Protective efficacy of vaccination against highly pathogenic avian influenza is dramatically suppressed by early infection of chickens with reticuloendotheliosis virus. Avian Pathology 38:31-34
Swayne DE, Kapczynski D (2008) Strategies and challenges for eliciting immunity against avian influenza virus in birds. Immunological reviews 225:314-331
Swayne DE (2009) Avian influenza vaccines and therapies for poultry. Comparative immunology, microbiology and infectious diseases 32:351-363
Swayne DE (2012) The role of vaccines and vaccination in high pathogenicity avian influenza control and eradication. Expert review of vaccines 11:877-880
Swayne DE (2012) Impact of vaccines and vaccination on global control of avian influenza. Avian diseases 56:818-828
Tian G, Zhang S, Li Y, Bu Z, Liu P, Zhou J, Li C, Shi J, Yu K, Chen H (2005) Protective efficacy in chickens, geese and ducks of an H5N1-inactivated vaccine developed by reverse genetics. Virology 341:153-162
Wei K, Sun Z, Zhu S, Guo W, Sheng P, Wang Z, Zhao C, Zhao Q, Zhu R (2012) Probable congenital transmission of reticuloendotheliosis virus caused by vaccination with contaminated vaccines. PloS one 7:e43422