0104 Lahi Newsletter Aug 08 Vol1

avianinsight A L O H M A N N A N I M A L H E A LT H N E W S B R I E F

August 2008

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Volume 1

Live attenuated vaccines: benefits of water stabilizers in drinking water and spray administrations We will continue to invest in research, development and production to assure a steady supply of high quality avian biologics for the poultry industry.

By Iván R. Alvarado, DVM, MS, Ph.D., ACPV, Technical Services Veterinarian, Lohmann Animal Health International

The increasing demand for economical and rapidly available sources of animal protein has highly influenced the constant growth of poultry operations around the world. The capacity of poultry to adapt to diverse geographical conditions and the fact that no large areas of land are required, have also contributed to the expansion poultry operations. As a result of their size increase, it has become necessary to develop and implement massive

inside

A poor administration is still the

tion of live attenuated vaccines.

most common cause of vaccine

The stimulation of immunity in a

failure in poultry. A successful

massively vaccinated popula-

administration of live attenuated

tion (herd immunity) reduces the

vaccines by spray or drinking

…the ease and low cost have made spray and drinking water the preferred methods for massive administration of live attenuated vaccines in the farms.

Introduction

and efficiency of commercial Dave Zacek President, Lohmann Animal Health

techniques for the administra-

Live attenuated vaccines p.1

probability of an individual bird

water requires an adequate

in a vaccinated flock to become

preservation and proper delivery

infected (Marangon and Busani

of the vaccine to the host. In

2006). Since under field condi-

this article, we describe the

tions, it is unrealistic to expect

adverse effects a live vaccine

a 100% protection of the birds

might encounter during resus-

in a vaccinated flock, the goal

pension and administration

is to develop immunity in a high

in suboptimal water, and the

enough proportion of birds to

benefits of using water stabilizers

prevent the transmission or

during vaccination.

minimize the adverse effects of ease and low cost have made

Massive Administration of Live Vaccines

spray and drinking water the

During manufacturing, most

preferred methods for massive

live attenuated vaccines are

administration of live attenuated

subjected to a lyophilization

vaccines in the farms.

process. Lyophilization, in

a disease agent. For poultry, the

President’s Note

p.4

association with adequate refrigeration

Periodic treatments of water wells with

through the bacterial cell membrane.

temperatures (between 4°C and 7°C

high concentrations of chlorine release

Once inside, the week acids dissociate

or 39°F and 44°F), guarantees the

products (CRP), and chlorination of the

and increase the acidification of the

preservation of an adequate vaccine

drinking water through in-line propor-

cytoplasm, affecting the bacterial

titer able to stimulate a satisfactory

tioners, have been effectively used in

survival in drinking water (Cotter and

immune response in the bird. However,

poultry operations to control microbial

Hill 2003). Furthermore, a synergistic

once reconstituted, the limited lifespan

levels. However, CRP also inactivate

effect between low water pH and

of live attenuated vaccines should be

live vaccines. Chlorinated compounds

the bacteriocidal/virucidal activity of

a major concern.

(such as sodium hypochlorite, chlorine

chlorine-released agents has been

dioxide and sodium dichloroisocyanu-

demonstrated. While low pH values

Drinking water is an appropriate method

rate) are highly active oxidizing agents,

(below 5) adversely affect water

of administration for live attenuated

destroying the cellular activity of proteins

consumption, high pH values can affect

vaccines that require an initial infection

(McDonnell and Russell 1999). Sodium

water palatability and form mineral

within the gut, such as Salmonella,

hypochlorite ionizes to produce Na+

deposits which reduce the water flow

infectious bursal disease and avian

and the hypochlorite ion OCL-, which

rate (Vermeulen, Backer et al. 2002).

encephalomyelitis vaccines. Also, due

is transformed in hypochlorous acid

to the communication of the nasal cavity

(HOCL), the active moiety responsible

Hardness is a measure of the quantity

with the mouth via the choanal cleft, a

for bacterial inactivation (McDonnell and

of salts, mainly of divalent ions such as

successful application of respiratory virus

Russell 1999). The deleterious effects

calcium, magnesium and/or iron, in the

vaccines (such as infectious bronchitis

of CRP on bacteria include a disruption

water. Hardness is expressed as mil-

and Newcastle disease virus) should

of oxidative phosphorylation and other

ligrams of calcium carbonate (CaCO3)

be expected. Coarse spray is a widely

membrane-associated activity as well as

per liter (ppm) and indicates the total

used and effective method to vaccinate

inhibition of DNA synthesis. Hypochlo-

quantity of divalent salts present (Wurts

birds against respiratory viruses, not

rous acid levels as low as 2.6 ppm

1993). However, high hardness in the

only at the hatchery but also in the

completely inhibit the growth of E. coli

presence of low calcium but high

farm. By coarse spray, the vaccine is

within 5 minutes, 96% of DNA synthesis

magnesium levels can be observed.

introduced through the eye, the nostrils

and between 10% and 30% of protein

A previous research study at Lohmann

and by ingestion after pecking.

synthesis (McDonnell and Russell 1999).

Animal Health has shown the detrimental

The virucidal activity of CRP includes

effect of hard water (20 ppm Fe and

nucleic acid fragmentation.

4 ppm NaOCl) on Newcastle disease

Adverse Conditions

virus and Salmonella typhimurium live

At the farm, a poor condition of the water used during resuspension and

pH is a measure of acidity or basicity of

vaccines two and four hours after

administration will have a detrimental

a solution. pH measurements depend

resuspension. Drastic reductions in viral

effect on vaccine titers. Live vaccines

on the concentration of hydrogen (H+)

and bacterial titers have been observed

should be resuspended in fresh water

and hydroxide ions (OH-). Waters with

2 and 4 hours after resuspension in

with a close to neutral pH, moderate

neutral pH (ph = 7.0), have an equal

hard water. In areas with hard water, the

hardness and no chlorine or other

concentration of H+ and OH-. The

constant deposit of insoluble minerals

disinfectant residues. The undesirable

resuspension of live vaccines in low pH

in the nipple drinkers and water lines

effects these factors will have on the

water will cause structural damage to

can also affect the homogeneous

survival of live vaccines are briefly

cell membranes and macromolecules

administration of live vaccines to the

described in the following paragraph.

such as DNA and proteins. Week acids,

flocks. Spray vaccination using hard

such as some organic acids used in

water can create mineral deposits,

drinking water for poultry, can pass freely

clogging the spray nozzles.

Water stabilizers

additive. Other reducing agents are

and administer the vaccines. Furthermore,

Live poultry vaccines are produced in

sodium metabisulfite, sodium bisulfite

the inclusion of dyes facilitates the visual-

specific pathogen free (SPF) embrion-

and ammonium thiosulfate

ization of vaccine in water lines and

ated eggs, tissue cultures or nutri-

(Simpson 2001).

vaccinated birds. The use of water

tional broths under controlled laboratory

stabilizers during vaccination allows a

conditions. Vaccine manufacturers have s pH buffering agents: used to stabilize the water pH between 6 and 7, approxrecognized the adverse conditions live

proper preservation of live vaccines, which, in association with a proper

vaccines face during their administration

imately. Some buffering agents include

administration technique, will contribute

in the farm. For such reason, the use

sodium phosphate, potassium phos-

to a successful vaccination.

of water stabilizers during vaccination is

phate, sodium citrate, sodium bicarbon-

recommended worldwide by technical

ate and potassium bicarbonate.

services veterinarians. s Water soluble dye: food colored dyes One of the first products used to

approved by the Food and Drug

stabilize the drinking water during

Administration are essential to allow

vaccination was skimmed milk. Dilution

the detection of the water containing

of skimmed milk (approximately 2

the live vaccines in the drinker systems

g/liter or 10 g/gallon) in the drinking

and in vaccinated birds (tongue and

water at least 20 minutes before the

nasal cleft after eye drop administration;

addition of the vaccine was a gen-

tongue, oral cavity or crop after water

eral recommendation (Cargill 1999).

administration, and skin and feathers

Skimmed milk has shown to efficiently

after coarse spray vaccination).

overcome the detrimental effects of chlorine. However, the presence of un-

s Thermo-stability conferring agents:

dissolved residues in cold water, which

bovine serum albumin, sorbitol,

can eventually block nipple drinkers,

maltose, lactose, sucrose and glycerol

and the presence of residues inside the

are some of the most common vaccine

water pipes after vaccination, serving as

stabilizers (Barbour, Abdelnour

a source of nutrients for bacterial growth

et al. 2002).

(build up of biofilms), has limited its use. More efficacious dyed water stabilizers

Conclusions

for the protection of live vaccines are

The administration of live attenuated vac-

commercially available. These are some

cines by massive methods such as drink-

of the characteristics and components

ing water and spray is a very common

used in water stabilizers:

practice in poultry operations. Massive

References Barbour, E. K., A. Abdelnour, et al. (2002). “Evaluation of 12 stabilizers in a developed attenuated Salmonella Enteritidis vaccine.” Vaccine 20 (17-18): 2249-2253. Cargill, P. (1999). “Vaccine administration in poultry.” In Practice 323-328. Cotter, P. D. and C. Hill (2003). “Surviving the acid test: responses of Gram-positive bacteria to low pH.” Microbiol. Mol. Biol. Rev. 67(3): 429-453. Marangon, S. and L. Busani (2006). “The use of vaccination in poultry production.” Rev. Sci. Tech. Off. Int. Epiz 26(1): 165-274. McDonnell, G. and D. Russell (1999). “Antiseptics and disinfectants: activity, action and resistance.” Clinical Microbiology Reviews: 147-149. Simpson, G. D. (2001). The reduction of the Chlorite ion. International symposium on chlorine dioxide., Las Vegas, Nevada. Vermeulen, B., P. D. Backer, et al. (2002). “Drug administration to poultry.” Adv. Drug Del. Rev. 54: 795-803.

administration methods are not as efficient sReducing agents: used to neutralize

as individual vaccination. However, they

oxidizing sanitizers (i.e. residual

offer several advantages, such as low cost

chlorine) or contaminants present

and rapid administration of one or several

in farm water. One of the most

vaccines. Since live attenuated vaccines

commonly used reducing agents is

are very fragile organisms, it is important

sodium thiosulfate (Simpson 2001),

to neutralize the adverse chemical agents

which is recognized as a safe food

present in the water used to resuspend

Wurts, W. A. (1993). “Understanding water hardness.” World Aquaculture 24(1): 18.

President’s Note hired additional staff are now fully

be completed by fall of 2009.

integrated and part of the vaccine manufacturing team in Maine. The

In addition, we are adding a fermentation

majority of our production consists of

suite in the manufacturing plant. This new

inactivated vaccines.

production addition will allow increased volumes of our bacterial products, both live

Increased demand for AviPro® vaccines

and killed.

both in the USA and internationally, Dave Zacek President, Lohmann Animal Health

It has been nearly one year since we opened our newly expanded production/testing/label, pack and ship site in Maine after having closed our Vineland site and transferred vaccine production to Winslow, Maine. Newly

require we build again. We have begun

Recognition of AviPro® quality is driving the

a large, state-of-the-art animal testing

demand. We are pleased that customers

complex on property adjacent to our

value our vaccines and keep demand-

current manufacturing plant in Winslow.

ing more year after year. We will continue

Included on the site are the Animal

to invest in research, development and

Services Administration Center, a large

production to assure a steady supply of

pen isolation unit, small test houses and

high quality avian biologics for the poultry

a large multiple isolation unit. Ground was

industry. And we will continue to work hard

broken for phase I of this project June

to be your Avian Professionals.

2008. The multi-million dollar facility will

375 China Road Winslow, Maine 04901

avianinsight

for more information: 207.873.3989

800.655.1342

www.lahinternational.com