Une présentation de: LABORATOIRE G.M.F. inc.

1-800-363-1339450-796-4772

10ièmeJournée Bovine4 juin 2004

Vaccinating for Respiratory Disease

Victor S. Cortese, D.V.M., Ph.D., Diplomat, ABVP (dairy Practice)Associate Director, Immunology - Cattle Veterinary OperationsPfizer Animal Health, Exton, PAVictor S. Cortese, D.V.M., Ph.D., Diplomat, ABVP (dairy Practice)Associate Director, Immunology - Cattle Veterinary OperationsPfizer Animal Health, Exton, PA

10e Journée Bovine4 Juin 2004

FACTORS AFFECTING THE IMMUNE RESPONSE

• STESS• STEROIDS• IMMUNODEFIENCIENCY DISEASES• DEVELOPMENT• AGING• NUTRTION

STRESS

• SHIPPING• WEATHER• CALVING• CASTRATION AND DEHORNING• WEANING• OTHER STESSES

In Utero Development

• Primordial thymus develops first, seen in calves between day 27-30

• Initial thymic cell infiltration are of unknown origin

• Primary CD4 and CD8 cell development occurs in the thymus

• Thymus reaches maximum size by mid-gestation

Neonatal immune system

• Capable of responding but immature and unprimed

• Systemic immune system well developed• Local immune system still developing

Neonatal immune systemmaturation

• T lymphocytes do not achieve peak levels until 8 months of age

• Phagocytic cells in higher numbers – but function not fully developed until 4 months

of age• Complement is 12-60% of adult levels

– reaches adult levels at six months of age• Systemic immune system well developed• Local immune system still developing

COLUSTRUM

• ESSENTIAL TO SURVIVAL• CONCENTRATE SOURCE OF PROTEINS,

VITAMINS, MINERALS, ESPECIALLY VITAMIN A, SUGAR

• CONTAINS ANTIBODIES, ONLY PROTECTION CALF HAS

• LAXATIVE• MUST GIVE ENOUGH EARLY• STIMULATION OF CALF’S OWN IMMUNITY

CALF MORTALITY (%)

02468

1012141618

1,1-6,2 6,3-12,0 12,1-19,3 19,4-46,7

BLOOD ANTIBODIES %

Colostrum has long term impacts on growth, health and production

What about colostral blockage of vaccination?

Blockage is determined by the following criteria

• 1. The disease itself, is it primarily CMI or humoral protection that affords protection?

• 2. The type of antigen MLV versus Killed• 3. The level of the existing antibodies• 4. Route of administration

NUTRITIONAL CONCERNS INCLUDE:

• MACROMINERALS(CALCIUM)• MICROMINERAL(SELENIUM,

COPPER, ZINC, CHROMIUM)• VITAMINS(VITAMIN A, VITAMIN E)

Anamnestic Response

0

50

100

150

Day 0 Day 14 Day 21 day 28

Antibody and T cellresponse

booster given on day 21

« UNFORTUNATELY, THE FACT THAT A VACCINE IS LICENSED

AND AVAILABLE DOES NOT MEAN THAT IT WORKS. »

• Ribble CS, Assembly vaccine efficacy.• Can Vet J Vol 31 October 1990

Viral DiseasesViral Diseases

• BVD• BVD• IBR• IBR• BRSV• PI3

• BRSV• PI3

BVD Virus Type

BVDBVD

Type 1Type 1 Type 2Type 2

Bovine viral diarrhea syndromes are caused by a group of related viruses.

BVD Immune Suppression

• Results in more severe disease– BRD (Bovine Respiratory Disease)

• BRSV• IBR • Pasteurella (Mannheimia) haemolytica

– Salmonella– Calf diarrhea

• Rotavirus

The majority of BVDV infections in the are unnoticed (subclinical)

Over 75% of all BVDV infections are subclinicalOften not noticedIn dairyand beef herds will show up as:

Reproductive failureCalf problems

pneumoniascours

BVD Disease SyndromesBVD Disease Syndromes

• Immune Suppression– Makes animals more susceptible

to other viruses and bacteria• Respiratory disease

• Immune Suppression– Makes animals more susceptible

to other viruses and bacteria• Respiratory disease

Reproductive form of BVDVReproductive form of BVDV

Persistent InfectionPersistent InfectionOnly occurs following in utero exposureOnly occurs following in utero exposure

Virus crosses the placenta before the immune Virus crosses the placenta before the immune system has developedsystem has developed

Calf learns to recognize the that strain of BVD Calf learns to recognize the that strain of BVD virus as part of selfvirus as part of self

Persistent Infection - Route

Persistently Persistently infectedinfectedfemale giving female giving birthbirth

Acute infection-pregnant female exposed to NCP

BVDV

(Wittum, et al, Prev Vet Med 49 (2001) 83-94)

93%

7%

Persistently Persistently Infected Infected calfcalf

Persistently infected CalvesPersistently infected CalvesMay be born weak and runtedMay be born weak and runted

May be born clinically normalMay be born clinically normal

Are immunologically frailAre immunologically frail

Are persistently infected forever Are persistently infected forever

Are the source of BVDV spread in most Are the source of BVDV spread in most herdsherds

May remain in the herd as cows and bulls May remain in the herd as cows and bulls spreading the virusspreading the virus

Outcomes of PersistenInfected Calv

• 50% of PI cattle will die within first year of life• Outcomes

– Death at/near time of birth– Death due to mucosal disease– Death from other cause but BVD immune

compromising was factor– Survive to maturity but less than healthy– Survive to maturity and reproduce

(Duffell & Harkness Vet Rec 117:240-245, 1985)

BVD EconomicsEffects of Persistent Infection

• 10 year farm profitability model– Reduced pregnancy rate (5%)– Increased preweaning mortality (10%) – Decreased weaning weight (0.5%)

• Economic effect was $14.85-$24.84 per yeardecreased return to fixed costs per beef cow exposed.

• Herd BVD control is economically beneficial in high risk herds

Larson, et al, Bov Pract 36(2) 106-112, 2002

BVDV Vaccines

• Will cross protect and decrease clinical disease and mortality

• Differences in reproductive protection• DOI 1 year + for MLV• DOI 6 months -1 year for inactivated• Some degree of maternal antibody blockage

Viral DiseasesViral Diseases

• BVD• BVD• IBR• IBR• BRSV• PI3

• BRSV• PI3

BHV-1

• Can cause severe respiratory disease• Immunosuppressive• Causes intracellular bridges – blocks

antibody neutralization• Other forms of BHV1 infections

BHV-1 Vaccines

• Many choices requires a strong cell mediated immune response

• Intranasal vaccines short durations of immunity, typically used immunomodulation

• DOI 6 months – 1 year

Viral DiseasesViral Diseases

• BVD• BVD• IBR• IBR• BRSV• PI3

• BRSV• PI3

BRSV

• Severe lower respiratory tract infections• Mild upper respiratory tract infections• Nutritional component• Forms syncytia – blocking neutralizing

antibodies

BRSV Vaccines

• Majority of information is on MLVs• The weakest of the four viral components• No local immunity stimulated• DOI 4-6 months• Limited systemic replication of the MLVs

What about Bacterins

Mannheimia haemolyticaPasteurella multocidaHemophilus somnusMycoplasma sp.Misc bacteria

Mannheimia haemolytica

• Can be a primary after stresses• Leukotoxin is primary virulence factor• Demonstrated blockage of immune

responses to Mannheimia bacterins in IBR sero-negative animals when MLV IBR was simultaneously administered

• Some questions concerning efficacy of these vaccines

Pasteurella multocida

• Never known to be primary invader even following a stress

• No good challenge model established for vaccine efficacy

• Questions concerning efficacy• Blockage has not been studied

Hemophilus somnus

• Respiratory Hemophilus is always secondary to another invader

• TEME only known primary syndrome• Reproductive syndrome is a big ?• No good challenge model for primary

infection

Mycoplasma species

• Still learning about this bacteria• No cell wall – need good antibiotic choices• Highly mutable• Is it a primary .. Trigger• Can it cause severe respiratory disease by

itself?• Good challenge models need to be

established

Thank you!!!!!!!!!!!!!