THE COVEXIN 10 STORYTHE COVEXIN 10 STORY

WHAT’S SO SPECIAL WHAT’S SO SPECIAL ABOUT COVEXIN 10?ABOUT COVEXIN 10?

WHAT’S SO SPECIAL ABOUT COVEXIN 10

• Adjuvant– 2 weeks of age– 3 months of age– 6 months of age– Sheep or cattle– 1 or 2 ml dose– Proven passive transfer– Proven to overcome maternal interference– Proven 1 year DOI– Single 1 or 2 ml dose for annual boost– 10 Clostridials per single dose

Aluminium Adjuvants

Point of Zero Charge• Aluminium Hydroxide 9.5 – 12.1• Aluminium Phosphate 4.6 – 4.7

How Does PZC Affect an Aluminum Adjuvant

PZC

+pH

How Does PZC Affect an Adjuvant

pH 7.2

pH

AlOOHPZC 9.5+

+

AlumPZC 4.5+

+

Point at Which TypicalVaccines are Blended

How Does PZC Affect an Adjuvant

pH 7.2

pH

AlOOHPZC 9.5+

+

AlumPZC 4.5+

+

Point at Which TypicalVaccines are Blended

Protein of Interest

+ PZC 5.5

0

How Does PZC Affect an Adjuvant

pH 7.2

pH

AlOOHPZC 9.5+

AlumPZC 4.5+

Point at Which TypicalVaccines are Blended

Protein of Interest+ PZC 7.8

+

+

Al3+

Al3+

Al3+

Al3+

Aluminum Hydroxide

Al3+

Clostridial Toxoids

Al3+

Al3+

Al3+

Al3+

Al3+

Clostridial ToxoidsAlum

Blending Blending

Alum vs. Aluminum Hydroxide

• Alum in Covexin 10– Very efficient process– Precipitated in presence of toxoids so

more antigen can be associated (trapped) in the gel

– Not as affected by charge interference as proteins are trapped, not bound solely by charge

– Better stability of proteins– Positively charged toxoids can still be

trapped in the matrix and associated with the adjuvant

– Can be autoclaved or filter sterilized on-site prior to blending with no effect on the adjuvant properties.

– Extremely higher potency– Blending involves a large drop in pH

which can be denaturing to the proteins, this has pros and cons.

• Aluminum Hydroxide– Passive process – Relies on

interaction between charge groups.– Like charges repel each other. Limited

amount of binding to adjuvant due to charge interference

– A lot of toxoids in clostridial vaccines will not be bound to the adjuvant because of steric hindrance

– Requires that all antigens be negatively charged to stick to the adjuvant. Toxoids having a net positive charge will be repelled.

– Preformed prior to blending and must be re-sterilized by heat. This process alters the adjuvant properties and is not consistent from batch to batch.

– Blending can be done without a change in pH, but more optimal binding can occur with a drop in pH during blending, depending upon the pI of proteins of importance.

WHAT’S SO SPECIAL ABOUT COVEXIN 10

• Adjuvant• Higher potency than competitors, even our

own.

CLOSTRIDIAL VACCINE POTENCY

Time

Pot

ency

3 yrs6 mosRequiredpotency

CLOSTRIDIAL VACCINE CLOSTRIDIAL VACCINE POTENCYPOTENCY

C. sordellii

0.0

5.0

10.0

15.0

0 10 20 30

Months

An

tib

od

y

resp

on

se (

U/m

L)

363028 1 st te st

363028 2nd te st

C. sordellii

0.0

5.0

10.0

15.0

0 10 20 30Months

An

tib

od

y

resp

on

se (

U/m

L)

363027 1 st te st

363027 2nd te st

CLOSTRIDIAL VACCINE POTENCY

Time

Pot

ency

3 yrs6 mosRequiredpotency

CLOSTRIDIAL VACCINE POTENCY

Time

Pot

ency

3 yrs6 mos

New PotencyLevel

RESULTING RELEASE LEVELSRESULTING RELEASE LEVELS

≥ 2.5 U/ml≥ 4.6 U/mlC. septicum

≥ 1.0 U/ml≥ 6.6 U/mlC. sordelli

≥ 2.5 U/ml≥ 4.9 U/mlC. tetani

≥ 3.5 U/ml≥ 6.0 U/mlC. novyi B

≥ 10.0 U/ml≥ 11.7 U/mlC. haemolyticum

Ph Eur passPh Eur passC. chauvoei

≥ 5.0 IU/ml≥ 5.3 IU/mlC. perfringens D

≥ 10.0 IU/ml≥18.2 IU/mlC. perfringens B & C

≥ 0.5 U/ml≥ 0.5 U/mlC. perfringens A

Potency:

EU Pharm Release Specification

Covexin 10 Release specification

Component

HOW DOES THIS HELP?Immune Response in Cattle to C. perfringens D antigen in different formulations

Day0 V1+Day28 V2+14 V2+14+1m V2+14+2m

Days

Uni

ts/m

L

SecondVaccination

MinimumPotency Level

FirstVaccination

EU MARKET COMPARISON EU MARKET COMPARISON TRIALSTRIALS

• Are our vaccines really that good?• Trials planned for 2005 in Spain

HOW THE TNT TEST WORKSHOW THE TNT TEST WORKS

Serum

+

Serum Toxin

(10 Units)

=

All toxin neutralized≥ 10 Antitoxin Units

Mouse dead≤ 10 Antitoxin Units

How Do We Stack Up Against the How Do We Stack Up Against the Leading Competitor?Leading Competitor?

Level of Protection For C. perf type C After Vaccination

0

2

4

6

8

10

Covexin 8 Vision 8

Nu

mb

er o

f C

alve

s O

ffer

ing

P

rote

ctio

n A

fter

Ch

alle

ng

e

10 IU ToxinChallenge

How Do We Stack Up Against the How Do We Stack Up Against the Leading Competitor?Leading Competitor?

Level of Protection For C. perf type C After Vaccination

0

2

4

6

8

10

Covexin 8 Vision 8

Nu

mb

er o

f C

alve

s O

ffer

ing

P

rote

ctio

n F

rom

Ch

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ng

e

5 IU ToxinChallenge

How Do We Stack Up Against the How Do We Stack Up Against the Leading Competitor?Leading Competitor?

Level of Protection For C. perf type D After Vaccination

0

2

4

6

8

10

Covexin 8 Vision 8

Nu

mb

er o

f C

alve

s O

ffer

ing

P

rote

ctio

n F

rom

Ch

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e

2 IU ToxinChallenge

How Do We Stack Up Against the How Do We Stack Up Against the Leading Competitor?Leading Competitor?

Level of Protection for C. perf type D After Vaccination

0

2

4

6

8

10

Covexin 8 Vision 8

Nu

mb

er o

f C

alve

s O

ffer

ing

P

rote

ctio

n F

rom

Ch

alle

ng

e

1 IU ToxinChallenge

How Do We Stack Up Against the How Do We Stack Up Against the Leading Competitor?Leading Competitor?

Level of Protection For C. novyi After Vaccination

0123456789

10

Covexin 8 Vision 8

Nu

mb

er o

f C

alve

s O

ffer

ing

P

rote

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rom

Ch

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e

0.5 U/mL ToxinChallenge

WHAT’S SO SPECIAL ABOUT WHAT’S SO SPECIAL ABOUT COVEXIN 10?COVEXIN 10?

• Manufactured in NZ using NZ Manufactured in NZ using NZ ingredientsingredients

WHAT’S SO SPECIAL ABOUT WHAT’S SO SPECIAL ABOUT COVEXIN 10?COVEXIN 10?

• Manufactured in NZ using NZ Manufactured in NZ using NZ ingredientsingredients

WHAT’S SO SPECIAL ABOUT WHAT’S SO SPECIAL ABOUT COVEXIN 10?COVEXIN 10?

• Manufactured in NZ using NZ Manufactured in NZ using NZ ingredientsingredients

• Media Production Plant on siteMedia Production Plant on site

WHAT’S SO SPECIAL ABOUT WHAT’S SO SPECIAL ABOUT COVEXIN 10?COVEXIN 10?

• Manufactured in NZ using NZ Manufactured in NZ using NZ ingredientsingredients

• Media Production Plant on siteMedia Production Plant on site• Continuous flow “Flash” steriliserContinuous flow “Flash” steriliser

WHAT’S SO SPECIAL ABOUT WHAT’S SO SPECIAL ABOUT COVEXIN 10?COVEXIN 10?

• Manufactured in NZ using NZ Manufactured in NZ using NZ ingredientsingredients

• Media Production Plant on siteMedia Production Plant on site• Continuous flow “Flash” steriliserContinuous flow “Flash” steriliser• 4000L scale fermenters4000L scale fermenters

WHAT’S SO SPECIAL ABOUT WHAT’S SO SPECIAL ABOUT COVEXIN 10?COVEXIN 10?

• Manufactured in NZ using NZ Manufactured in NZ using NZ ingredientsingredients

• Media Production Plant on siteMedia Production Plant on site• Continuous flow “Flash” steriliserContinuous flow “Flash” steriliser• 4000L scale fermenters4000L scale fermenters• Computer controlled fermentationsComputer controlled fermentations

WHAT’S SO SPECIAL ABOUT WHAT’S SO SPECIAL ABOUT COVEXIN 10?COVEXIN 10?

• Manufactured in NZ using NZ Manufactured in NZ using NZ ingredientsingredients

• Media Production Plant on siteMedia Production Plant on site• Continuous flow “Flash” steriliserContinuous flow “Flash” steriliser• 4000L scale fermenters4000L scale fermenters• Computer controlled fermentationsComputer controlled fermentations• Toxin production monitored though a Toxin production monitored though a

unique liquid chromatography processunique liquid chromatography process

WHAT’S SO SPECIAL ABOUT WHAT’S SO SPECIAL ABOUT COVEXIN 10?COVEXIN 10?

• Manufactured in NZ using NZ ingredientsManufactured in NZ using NZ ingredients• Media Production Plant on siteMedia Production Plant on site• Continuous flow “Flash” steriliserContinuous flow “Flash” steriliser• 4000L scale fermenters4000L scale fermenters• Computer controlled fermentationsComputer controlled fermentations• Toxin production monitored though a unique Toxin production monitored though a unique

liquid chromatography processliquid chromatography process• Continuous feed centrifugationContinuous feed centrifugation

WHAT’S SO SPECIAL ABOUT WHAT’S SO SPECIAL ABOUT COVEXIN 10?COVEXIN 10?

• Ultrafiltration/Diafiltration processUltrafiltration/Diafiltration process

WHAT’S SO SPECIAL ABOUT WHAT’S SO SPECIAL ABOUT COVEXIN 10?COVEXIN 10?

• Ultrafiltration/Diafiltration processUltrafiltration/Diafiltration process• 6000L blending vessels6000L blending vessels

WHY IS COVEXIN 10 BETTER WHY IS COVEXIN 10 BETTER THAN ULTRAVAC, ETCTHAN ULTRAVAC, ETC

• New technologyNew technology• 2 week age claim2 week age claim• Neonatal coverageNeonatal coverage• Proven to work in the face of maternal Proven to work in the face of maternal

interferenceinterference• NZ ingredients/manufacturingNZ ingredients/manufacturing• Low dose/less crap in the vaccineLow dose/less crap in the vaccine• Cell free (except for C. chauvoei)Cell free (except for C. chauvoei)• Complete Coverage for all possible clostridiaComplete Coverage for all possible clostridia• Meets modern regulatory requirementsMeets modern regulatory requirements