Issue No.34 / January 2011

The Vector Vaccines Technology in Poultry :The Vector Vaccines Technology in Poultry :The Vector Vaccines Technology in Poultry :The Vector Vaccines Technology in Poultry :

A New Era Has ArrivedA New Era Has ArrivedA New Era Has ArrivedA New Era Has ArrivedBy Christophe CAZABAN, DVM ~ Scientific Direction O fficer ~ CEVA Santé Animale, France

CEVA Santé Animale has held a scientific symposium on vector vaccines technology applied in poultry production in San Diego, California on October 6-8, 2010. External researchers, field practitioners, as well as Ceva scientists displayed their experience in using vector vaccines and the obtained benefits. More generally, the perspectives in terms of better, stronger, and more accurate immunization against several major poultry diseases have been highlighted.

DEFINITIONS

When constructing a vector vaccine, the first step is to select a vector, or carrier. Usually, it is an attenuated microorganism deprived of any residual virulence, or naturally non-pathogenic for chickens. Currently, the most commonly used vectors in the poultry industry are the fowlpoxvirus (FP) and the herpesvirus of turkeys (HVT). In the future, other viral or bacterial vectors may be selected as well.

The relevant immunogen (the “protective factor”) of a targeted pathogen and the corresponding gene (the “protective gene”) encoding for it need to be identified. This gene is in vitro inserted into the genome (DNA) of the vector virus in a compatible insertion site, and associated with a specific promoter. During the natural replication cycle of the vector, the promoter will ensure the translation of the inserted gene into the corresponding antigenic protein (immunogen) that will be expressed like in its original organism.

As a result, the vaccinated bird is immunized against two diseases, because it will develop an immune response to both the vector and the immunogen that is encoded by the inserted gene.

Fig.1: Schematic representation of the design of a live HVT-vector Newcastle disease vaccine.

Why Developing Vector Vaccines?

The vector vaccines technology provides several significant improvements compared to the conventional approach:

• Ensuring a successful vaccine take without any interference with the maternally-derived antibodies, e.g., using HVT vector in cell-associated (frozen) form; this has obvious assets in terms of hatchery vaccination either by in ovo route three days before hatch, or by subcutaneous route at hatch;

• Safer vaccines than some conventional live ones: vector vaccines avoid the vaccine rolling infections that can be observed due to the poor vaccination coverage of the flock, and to the extensive spread of the vaccine strain e.g., when vaccinating against Newcastle disease by using pneumotropic strains (La Sota, Hitchner B1); as an evidence, the US producers are usually vaccinating their chicken flocks with the aim to minimize the respiratory reactions due to the massive usage of Hitchner B1 strain;

• Safer vaccines than some conventional inactivated ones; in particular, oil-emulsion vaccines intended to young (day-old) chicks may still present some tolerance issues to the bird per se, or due to the quality of the injection; on the contrary, vector vaccines are adjuvant-free;

• Developing of vaccine types that do not exist today, e.g., live avian influenza (AI) vaccines;

• Vector vaccines enable to differentiate infected from vaccinated animals (DIVA concept). This is particularly required when vaccinating against Mycoplasma gallisepticum (MG) for instance. Briefly, the vaccinated birds will be protected and still remain seronegative in the official control tests.

Is There Any Risk in Using A Vector Vaccine?

These new generation vaccines are subjected to more tests in the laboratory than conventional ones, because there are several additional trials that are requested by the regulatory authorities. These tests are especially intended to address the stability of the genetic construct in vitro (in cell culture) and in vivo (in chickens).

As a consequence, the vector vaccines are much safer and more stable than conventional live vaccines that may revert to virulence, induce post-vaccination reactions, and “roll” throughout flocks which is critical in a multi-age complex. Due to the high safety profile and the non-spreading character of vector vaccines, the quality of administration is key.Because of the required more extensive set of tests, the vector vaccines are known in details, on the antigenic but also on the genetic level. They are probably better known than the conventional live vaccines that are attenuated through several passages in culture substrate, without knowing what are the exact antigenic changes due to these attenuation passages.

On the other hand, a live vector vaccine instead of a conventional killed oily vaccine (eg, AI) enables a better local tolerance, and a higher operator’s safety.

Lastly, tests are comparing the vector vaccine to its “parent” virus (eg, HVT) to ensure that the insertion of a foreign gene did not induce any change in the biological features (safety / efficacy) of the carrier.

Where Are These Vector Vaccines Used?

First they represent a real breakthrough in human medicine in the prevention of human flu. They should offer a broader spectrum of protection, which reduces the need to develop new formulas every year in the human flu vaccine.

Another major step is to avoid the usage of embryonated hen eggs for the propagation of the influenza virus, which is responsible for allergic reactions to egg proteins in some people. Last but not least, they are quicker to produce in large quantities.

In veterinary medicine, there are already many vaccines on the market, based on the vector vaccines technology: for pets, livestock, and poultry.

Avian vector vaccines are already used in the United States, in Europe, and in an increasing number of countries worldwide.

A Breakthrough Prevention Tool Against Newcastle Disease: Vectormune HVT-NDV

Newcastle disease remains one of the major issues the poultry industry has to face, notwithstanding the significant improvements that have been made in the past years in biosecurity, monitoring, diagnosis and vaccination programs. This means that there is still room to improve the immunization status (strength and duration) of the poultry flocks.One of the major obstacles is the obligation to immunize as early as possible because the birds are susceptible throughout their entire life (there is no age-related resistance); however, in endemic areas like South-East Asia, the Middle East or Latin America, day-old chicks do carry a significant amount of maternally-derived antibodies (MDA) that partly interfere with the proper vaccine take at hatch. Uneven protection after vaccination is therefore obtained which constitutes a threat to the flock’s performances.

In addition, inactivated oil-emulsion vaccines are usually recommended to increase the immune status, compared to the use of live attenuated vaccines only. This approach is providing significant improvements. However, the MDA do also affect the vaccine take of inactivated vaccines. These killed vaccines must be injected, which represents an additional operation inside a hatchery, which is not always easy to implement without damaging the whole chicks delivery process.

The advent of the vectorization technology based on the HVT (herpesvirus of turkey) vector in cell-associated form enables to address and improve the following issues:

• Its cell-associated (frozen) form enables the vaccine to take in the presence of maternally-derived antibodies. This is valid for MDA against the vector (Marek MDA) and against the inserted gene (Newcastle MDA);

• Its mechanism is to get integrated into cells where it strongly stimulates both the humoral and cellular immune responses: the elicited immunity is deeper;

• It is regularly released into the bloodstream (“viraemia”) before entering new cells: this process is lasting for the entire chicken’s life: therefore, the immune system cells (the memory cells in particular) are permanently stimulated: the elicited immunity is stronger and longer.

• Although some hatcheries may not be familiar with the liquid nitrogen logistics (especially some broiler hatcheries), the proven perspectives in terms of better control of ND do justify to consider this option.

The early immunization using Vectormune HVT-NDV with an apathogenic ND vaccine (Cevac Vitapest L) is the successful combination to start with: the conventional live vaccine will stimulate the local receptors in the upper respiratory tract, after spray administration, enabling an early local immunity, whereas Vectormune HVT-NDV will start its cycle of virus integration and release.

The epidemiology of ND is not uniform in the different parts of the world: of minor risk in some areas, of major risk in some others. Therefore, an adapted vaccination program can be designed on a case by case, including the use of some boosters, if needed.

CONCLUSION

As a conclusion, the vector vaccines offer a real breakthrough innovative approach of prevention programs in poultry farming. These vaccines are globally safer than the conventional ones. In addition, they are more efficient: they do not only confer a protection against the disease, but they also contribute to significantly make the vaccination programs easier. In some instances, they enable to differentiate vaccinated from infected animals.

Convenient administration, simpler vaccination programs, efficacy and better safety all contribute to better performances and costs savings. This is one step ahead in a global disease control on a flock basis.

For more information and to view the Vector vaccines scientific web-seminar please go to www.vector-vaccines.com

Fig 2 : Current list of Ceva’s vector vaccines for poultry

The 1st Ceva Vector VaccinesSymposium was attended by

280 people from 41 countries and

created a unique platform to share

experiences between key note speakers

and guests on this new technology in

control of poultry diseases.

The world leader in vector vaccine technology

Access the free web-seminar showing the symposium at

www.vector-vaccines.com

Vector Vaccines Symposium