Issue No.

34 / January 2011

The Vector Vaccines Technology in Poultry :

A New Era Has Arrived
By Christophe CAZABAN, DVM ~ Scientific Direction Officer ~ CEVA Sant Animale, France

CEVA Sant 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 fowlpox
virus (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 operators 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 flocks 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 chickens 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 Cevas vector vaccines for poultry

Vector Vaccines
Symposium

The 1st Ceva Vector Vaccines

Symposium 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.

Access the free web-seminar

showing the symposium at

www.vector-vaccines.com

The world leader in vector vaccine technology