Hatchery vaccination by Grupo Asís

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Servet (División de Grupo Asís Biomedia S.L.) Centro Empresarial El Trovador, planta 8, oficina I Plaza Antonio Beltrán Martínez, 1 • 50002 Zaragoza (España) Tel.: +34 976 461 480 • Fax: +34 976 423 000 • www.grupoasis.com

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Hatchery vaccinati n Mohamed Faizal Abdul-Careem

The publishing strength of Grupo AsĂs Editorial Servet, a division of Grupo AsĂs, has become one of the reference publishing companies in the veterinary sector worldwide. More than 15 years of experience in the publishing of contents about veterinary medicine guarantees the quality of its work. With a wide national and international distribution, the books in its catalogue are present in many different countries and have been translated into nine languages to date: English, French, Portuguese, German, Italian, Turkish, Japanese, Russian and Chinese. Its identifying characteristic is a large multidisciplinary team formed by doctors and graduates in Veterinary Medicine and Fine Arts, and specialised designers with a great knowledge of the sector in which they work. Every book is subject to thorough technical and linguistic reviews and analyses, which allow the creation of works with a unique design and excellent contents. Servet works with the most renowned national and international authors to include the topics most demanded by veterinary surgeons in its catalogue. In addition to its own works, Servet also prepares books for companies and the main multinational companies in the sector are among its clients.

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Hatchery vaccination

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Hatchery vaccinati n Mohamed Faizal Abdul-Careem

Author: Mohamed Faizal Abdul-Careem. Format: 17 x 11 cm. Number of pages: 62. Number of images: 37. Binding: paperback, wire-o.

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The number of new technology vaccines available has been increased worldwide, as well as their widespread use in the poultry industry, especially at hatchery level. Therefore, an updated review with practical and visual approachs has been developed in order to highlight the importance of hatchery vaccination in poultry farming, whatever the vaccination technique used (in ovo, subcutaneous or spray vaccination), to control the main diseases affecting this species (infectious bursal disease, Newcastle disease, infectious laryngotracheitis, etc.). This handbook has been written by an expert with a wide experience in this field. Numerous graphic resources have been included to complement the information provided and make the contents more understandable and accessible to readers.

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Hatchery vaccination

Presentation of the book Newly hatched chicks are placed in the barn when they are less than 3 days old. Since then, they are exposed to various pathogens in the contaminated barn environment. The generation of vaccine mediated immune responses requires at least 6–7 days to be mounted, and the earlier the vaccination, the better the protection of chicks. In this regard, vaccination before placing them in the barn environment or “hatchery vaccination” is gaining increasing attention. The goal of hatchery vaccination is to empower or at least to prime the chick’s immune system by the time of placing the chickens in the contaminated barn environment. Since there is evidence that hatchery vaccination also mounts quick innate immune responses, there is a chance that the stimulated innate host responses lead to protection until solid antigen specific adaptive immune responses are generated. Additional consideration of employing hatchery vaccination may be the 1) increasing the vaccine coverage and vaccination efficiency and 2) decreasing the cost of production. On the other hand, the limitations of hatchery vaccination may include the potential overload of the developing immune system of the chick very early and possible interactions among vaccines that are introduced in the hatchery. Disease control maintaining the health of chickens allowing them to express their full genetic potential is a pre-requisite for the profitability of poultry farming. Hatchery vaccination plays a significant role in poultry disease control. The objective of this book is to provide an overview of hatchery vaccination in poultry farming including the immune mechanisms, techniques, precautions, advantages and limitations.

Mohamed Faizal Abdul-Careem

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Hatchery vaccination

The author Mohamed Faizal Abdul-Careem Dr. Mohamed Faizal Abdul-Careem is Assistant Professor (virology) at the University of Calgary (Canada) since 2010. He has obtained his basic veterinary degree (BVSc) from the University of Peradeniya (Sri Lanka) and a Master of Veterinary Medicine degree (MVM) from the University of Glasgow Veterinary School (UK) in 1995. He completed his PhD degree from the University of Guelph (Canada) in 2008. His doctoral thesis entitled “Characterization of Host Responses Following Marek’s Disease Virus Infection or Vaccination Against Marek’s Disease”. Following his PhD degree, he was awarded a prestigious Canadian Institutes of Health Research Fellowship to conduct post-doctoral research on innate immune responses generated against mucosal viral infections at the Center for Gene Therapeutics of the McMaster University (Canada). He is diplomate of American College of Poultry Veterinarians (ACPV) and American College of Veterinary Microbiologists (ACVM). He has expertise and strong interests in the area of avian viral immunology. He has around 31 manuscripts published in peer-reviewed journals and 90 % of these manuscripts are on avian viral immunology. His research programme at the University of Calgary is supported by grants from Canadian federal, provincial and poultry industry sources such as Natural Sciences and Engineering Research Council of Canada, Alberta Livestock and Meat Agency (ALMA), and Canadian Poultry Research Council. He has established stateof-the-art research facility for his experimental animal and laboratory work at the University of Calgary.

Communication services Website Online visualisation of the sample chapter. Presentation brochure in PDF format. AuthorÂ´s CV. Sample chapter compatible with iPad.

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Hatchery vaccinati n Mohamed Faizal Abdul-Careem

Table of contents 1. Introduction General definition History Economic significance

2. Development of immune system General overview Innate immune system development Development of innate immune functions Cell-mediated immune system development Development of cell-mediated immune functions Antibody-mediated immune system development Development of antibody-mediated immune functions Gut-associated lymphoid tissue (GALT) development

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Development of adaptive immune responses in GALT

3. Immune responses to hatchery vaccination General overview

6. Hatchery vaccination techniques In ovo vaccination

Innate immune responses

In ovo vaccination leads to induction ofÂ mucosal immune responses

Adaptive immune responses

Currently available in ovo vaccines

Cell-mediated immune responses Antibody-mediated immune responses

4. Hatchery vaccination Overview Differences between hatchery and field vaccination Current trends of hatchery vaccination practices Practice of in ovo vaccination by broiler chicken industry

5. Hatchery vaccines Currently available hatchery vaccines Attributes of acceptable hatchery vaccines Safety

Vectored vaccines Hatchery spray vaccination Currently available spray hatchery vaccines

Hatchery subcutaneous vaccination

7. Management of hatchery vaccination Practices during pre-vaccination period Practices during post-vaccination period

8. Advantages of hatchery vaccination 9. Limitations of hatchery vaccination

Compatibility among hatchery vaccines Ability to withstand maternal antibody interferences Ability to induce innate responses Persistence of vaccine antigens Ability to induce adaptive responses and protection

10. References

Development of immune system

Hatchery vaccination

General overview Since hatchery vaccination is centred on ED 18 pre-hatch and D 1 post-hatch, the status of development of immune system (innate and adaptive) and immune functions during this period determine the outcome of vaccination. It appears that the development of immune system and its functions are not as optimum as in adult chickens until early post-hatch period.

ED 18

D 1

D 8–12

Immune system organ development Adaptive immune response generation Quality of adaptive immune responses

Figure 2. The status of development of immune system organs and adaptive immune functions are not as optimum as in adult chickens when hatchery vaccination is performed.

DEVELOPMENT OF IMMUNE SYSTEM

Innate immune system development Innate immune system development, including the innate immune cells, innate immune receptors (Tolllike receptors or TLRs) and effectors such as type I and III interferons (IFNs), is completed around the time of hatchery vaccination.

Innate receptors (i.e. TLRs)

Type I and III IFN receptors Type I and III IFNs Macrophages ED 9

ED 12

ED 15

ED 18

Figure 3. Development of various components of the innate immune system during pre- and post-hatch periods.

Development of immune system

Hatchery vaccination

Development of innate immune functions Innate immune stimulants administered into ED 18 eggs and D 1 chickens are capable of inducing potent and transient innate immune responses pre- and post-hatch. Similarly, live, attenuated and vectored vaccines are expected to induce potent innate responses in the host, since the organisms are capable of replication or multiplication.

Higher macrophages and other

innate cells

Higher pro-inflammatory

mediators

In ovo hatchery vaccination

Innate immune responses pre-hatch and D 1 post-hatch

Figure 4. Live, live attenuated and vectored vaccines are capable of inducing innate host responses leading to protection until adaptive immune responses are generated.

DEVELOPMENT OF IMMUNE SYSTEM

Cell-mediated immune system development Development of T lymphocyte colonisation of the main primary lymphoid organ involved in cell-mediated immune responses (thymus) is close to be completed just after hatch. The secondary lymphoid organs acquire the T lymphocytes necessary for the functions during the early post-hatch period.

Table 2. Time scale of the formation of the primary lymphoid organ (thymus) and its colonisation by T lymphocytes during pre- and post-hatch periods. ED 18–early ED 3 ED 6–8 ED 12 ED 12–14 post-hatch period Beginning of development of the thymus First wave of T lymphocyte colonisation Well-developed cortex and medulla Second wave of T lymphocyte colonisation Third wave of T lymphocyte colonisation

Immune responses to hatchery vaccination

Hatchery vaccination

General overview Currently, killed vaccines are used rarely in the hatchery. The vaccines used at hatchery are mostly live, live attenuated and vectored (fowlpox and HVT). Since these vaccines are capable of replication or multiplication, they may induce innate host responses almost immediately following vaccination. However, optimal adaptive immune response generation appears to be delayed due to the incomplete development of adaptive immune system (its structure and functions) by the time of hatchery vaccination.

Vaccine organism

Natural killer (NK) cell

Cytokines

Vaccine antigen

Pro-inflammatory cytokines

Antibody

Macrophage

T cell

IMMUNE RESPONSES TO HATCHERY VACCINATION

Availability of vaccine antigen

Innate response due to vaccine replication or multiplication

Cell-mediated immune response

Antibody-mediated immune response

ED 18

Figure 8. The development and functions of adaptive immune system are not optimum to elicit the antigen-specific immune responses by the time of hatchery vaccination. Thus, the combination of innate and adaptive immune responses protects the chickens once they have been vaccinated at hatchery.

Immune responses to hatchery vaccination

Hatchery vaccination

Innate immune responses Once hatchery vaccination has been carried out, innate immune responses may play a substantial role protecting the chickens during the early post-hatch period. Most of the hatchery vaccines are based on introducing organisms with the ability to induce a mild infection, in order to create potent innate host responses (in response to vaccine organism replication or multiplication) within the hours following vaccination. Such antimicrobial responses are mediated through innate receptor (i.e. TLR) signaling pathways and may persist at least for a few days post-hatch until adaptive immune responses are elicited.

IMMUNE RESPONSES TO HATCHERY VACCINATION

Vaccine organism entry into host cells (i.e. vaccine virus) Vaccine organism TLR 5

Endosome

Vaccine organism-associated molecular patterns

TLR 1

TLR 4 TLR 3

TLR 7

TLR 2 TLR 21

NK cells

Hatchery vaccination

Transcription of antiviral genes

21 Type I IFNs

Nucleus Inhibition of microbial infections

Transient protection from microbial challenges encountered after hatch

Nitric oxide (NO)

Macrophages

Figure 9. Induction of innate responses following hatchery vaccination that culminate in antimicrobial responses.

IFN-γ

Hatchery vaccination

Overview D 1 chickens are placed in the poultry barn environment following the hatch. Upon placement, the chicks may be exposed to numerous pathogens via several routes (ocular, respiratory, oral and cutaneous). Salmonella spp. Escherichia coli Clostridium spp. Mycoplasma spp. Haemophilus paragallinarum Bordetella spp. Chlamydia spp. Pasteurella multocida

Infectious bronchitis virus Infectious bursal disease virus Infectious laryngotracheitis virus Newcastle disease virus Chicken anaemia virus Marek’s disease virus Avian poxvirus Avian leucosis virus Avian encephalomyelitis virus Inclusion body hepatitis virus Egg drop syndrome virus

Eimeria spp. Helminths

Figure 12. The transfer of D 1 chicks from hatchery to barn exposes them to a wide range of pathogens.

HATCHERY VACCINATION

Differences between hatchery and field vaccination Hatchery vaccination is performed before placing the chickens in the contaminated barn environment. Due to the early induction of host responses, these chicks are better protected compared with those vaccinated in the field as field vaccination is performed once the birds have been potentially exposed to pathogens. 27

In ovo vaccination

Spray vaccination

Subcutaneous vaccination

Hatchery vaccination Before being exposed to pathogens

Spray vaccination

Exposure to pathogens At the poultry barn

Subcutaneous vaccination

Field vaccination After being potentially exposed to pathogens

Better vaccine-mediated protection with hatchery vaccination Figure 13. Hatchery vaccination may induce early host responses in D 1 chickens before being exposed to potential pathogens.

Hatchery vaccination

Current trends of hatchery vaccination practices Hatchery vaccination, particularly in ovo vaccination, has been mainly adapted by the broiler chicken industry because it uses both sexes for rearing. Once female birds are separated in layer industry, the use of other means of hatchery vaccination (coarse spray and subcutaneous routes) is feasible. Table 5. Currently, in ovo vaccination is difficult to perform in layer chickens (unlike in broilers); however, other hatchery vaccination techniques can be applied in layers. 28

Broiler industry

Layer industry

In ovo vaccination

Spray vaccination

Subcutaneous vaccination

HATCHERY VACCINATION

∼ 100 % ∼ 55 %

∼ 50 %

WESTERN EUROPE

ASIA

NORTH AMERICA

∼ 100 %

Hatchery vaccination, particularly in ovo vaccination, is practised mainly in North and Latin America, followed by Asia, Europe, Africa and Middle East. Approximately 65 % of world’s broiler chicken population is hatchery vaccinated.

CENTRAL AND EASTERN EUROPE

∼ 20 %

Practice of in ovo vaccination by broiler chicken industry

∼ 35 %

AFRICA AND MIDDLE EAST LATIN AMERICA

Figure 14. In ovo vaccination is mainly practised in North and Latin America and it is gaining acceptance worldwide.

Hatchery vaccines

Currently available hatchery vaccines

Hatchery vaccination

Table 6. Currently available hatchery vaccines.

Nowadays, a number of viral, bacterial and parasitic hatchery vaccines are available for controlling economically important poultry diseases and they can be administered via in ovo, coarse spray and subcutaneous routes.

In ovo

D 1 spray

D 1 subcutaneous

MD IB IBD

ND ILT Fowlpox Coccidiosis Salmonella spp. Escherichia coli

HATCHERY VACCINES

Ability to induce adaptive responses and protection

31 Ab ma ility to te inte rnal awiths rfer ntib tand enc od es y

Some attributes of hatchery vaccines of ce ns ten ge sis nti Per cine a vac

Hatchery vaccines should possess a number of unique features because they are employed during the late embryo development and the early post-hatch period.

Safety to lity ate Abi ce innses u n indrespo

Attributes of acceptable hatchery vaccines

Com pat ibil ity

Figure 15. Hatchery vaccines should possess some unique features in order to induce protective responses against different poultry diseases.

Hatchery vaccines

Hatchery vaccination

Safety Currently available hatchery vaccines, particularly in ovo vaccines, do not negatively influence the hatchability (Fig. 16). Replicating vaccine organisms are used as hatchery vaccines and their replication in late-term embryo and during early posthatch period should induce minimal or no clinical consequences (Fig. 17).

In ovo vaccination MD vaccines Immune complex vaccine against IBD Herpesvirus- and fowlpox-vectored vaccines

Hatchery vaccination with attenuated or nonpathogenic live organisms The effect of these hatchery vaccines on hatchability is negligible

Figure 16. Currently available in ovo vaccines, such as those against MD, IBD and also vectored vaccines, do not affect the hatchability of eggs.

Replicating or multiplying vaccine organisms induce minimal or no reactions

Figure 17. Almost all the hatchery vaccines are live or attenuated organisms and their replication should induce minimal or no clinical consequences.

HATCHERY VACCINES

Compatibility among hatchery vaccines Nowadays, a number of viral, bacterial and parasitic vaccines are available to be used between ED 18 and D 1 using various routes, and the potential interactions among these vaccines may lead to vaccination failures.

ED 18

D1 D1

Hatchery vaccination within a period of 4 days

Viral (n = 6), bacterial (n = 2) and parasitic (n = 1) available vaccines

A number of in ovo vaccines should be administered simultaneously

There may be potential interactions among viral, bacterial and parasitic vaccines

Different spray and subcutaneous vaccines should be applied the day of hatch

Developing immune system should be able to withstand the antigen load

Figure 18. Hatchery vaccination is practised within a small window of time with a number of vaccines to be administered. Potential interferences among these vaccines may lead to vaccine efficacy problems.

Hatchery vaccination techniques

Hatchery vaccination

Vaccine is deposited in the amniotic cavity

In ovo vaccination

In ovo vaccination targets ED 18 embryos. The vaccine is delivered into the amniotic cavity with an accuracy of more than 95 % and its uptake into the embryo is via oral, cloacal and respiratory routes.

C E 38

Vaccine uptake by the embryo

Figure 23. In ovo vaccination involves delivering the vaccine into the amniotic cavity, where it will be absorbed by the embryo via oral, cloacal and respiratory routes. A, B, C, D and E represent air sac, chorioallantoic membrane, amniotic cavity, yolk sac and embryo, respectively.

HATCHERY VACCINATION TECHNIQUES

In ovo vaccination leads to induction of mucosal immune responses In ovo vaccination aims to deliver the vaccine onto the mucosal surfaces of gastrointestinal and respiratory tracts.

Immune responses post-hatch In ovo vaccination at ED 18

CD8 cytotoxic T cells Antibody

Induction of both innate and cell- and antibody-mediated immune responses locally in the respiratory and gastrointestinal tracts

Figure 24. In ovo vaccination may lead to the induction of cell- and antibodymediated immune responses in addition to innate host responses in the respiratory and gastrointestinal systems.

Hatchery vaccination techniques

Hatchery vaccination

Currently available in ovo vaccines MD vaccine MD vaccine was the first ever in ovo vaccine made available for the poultry industry. MD vaccines are cell associated and can withstand the maternal antibody levels without compromising the vaccine efficacy during the early post-hatch period. Although the exact underlying mechanisms of the vaccine-induced protection against MD virus (MDV) are unknown, it is believed that chickens are protected due to the elicitation of both innate and adaptive immune responses. 40 NO

NK cell IFN-Îł

Days post-vaccination

Cytotoxic TÂ lymphocytemediated killing

Antibody-dependent cell-mediated cytotoxicity

Macrophage Reduce MDVinfected cells

Reduce MDV-infected cells 3

Figure 25. Proposed mechanism of host responses induced by in ovo MD vaccine, which involves both innate and adaptive immune responses.

HATCHERY VACCINATION TECHNIQUES

IBD vaccine In ovo immune complex vaccines against IBD are protected from maternal antibody interferences because the vaccine virus is protected from immune complex antibodies (Fig. 26). The decay of immune complex antibodies over time allows vaccine virus to replicate at a low maternal antibody levels. At around 3 weeks of age, vaccine virus-mediated antibody production begins leading to protection of vaccinated chickens against IBD, once maternal antibody levels are also waned (Fig. 27). Vaccination with naked viral particles 1:500 1:250 1:125

Age 0

Vaccination with antibody-virus immune complexes

Maternal antibody titer

3 weeks

Vaccine virus neutralisation

6 weeks

1:500 1:250 1:125

Age 0

3 weeks

6 weeks

Vaccine virus is protected as far as antibodies are attached with the virus particles

Figure 26. Immune complex vaccines can withstand maternal antibodies compared with naked viral vaccines against IBD.

Presentation brochure

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Hatchery Vaccinati n Mohamed Faizal Abdul-Careem