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 , in Pakistan against H7N1 in 2003-2004 , in USA against LPAIV H7N2 in 2003 , and in Korea against H7N7 in 2005 . Recently, inactivated H7N3 vaccines were used in Mexico to control the ongoing outbreaks of HPAI H7N3 since 2012 . 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 . Currently, four countries use different H5N1 vaccines in poultry: China since 2004, Indonesia since 2004, Vietnam since 2005 and Egypt since 2006 . Occasionally, vaccines for HPAI H5N1 have been used for short periods in Cote d’Ivoire, France, Kazakhstan, Mongolia, Netherlands, Pakistan, Russia and Sudan . Furthermore, more than 10 countries used inactivated H9N2 vaccines in poultry like China since 1998 , Korea since 2007 , Israel since 2003  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 . The use of bivalent H5-H7 and H7-H9 inactivated vaccines were used in Italy  and Pakistan , 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 .
- Vaccine-induced antibodies hinder routine serological surveillance and differentiation of infected birds from vaccinated ones requires more advanced diagnostic strategies .
- 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 
- 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 .
- 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 , avian reticuloendotheliosis virus [16, 57], avian leukosis virus  or avian paramyxoviruses  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.
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Read Part 1- A view and an overview on the control of avian influenza outbreaks in poultry: (1-6) Mass-culling of birds (personal experience)