REWRITING THE BOOK ONBRD TREATMENT

Zelnate™ DNA Immunostimulant is a new chapter in BRD management

Significant progress has been made in the fight against bovine respiratory disease (BRD), yet veterinarians and producers still struggle to manage losses associated with BRD.

Bayer HealthCare Animal Health set out to meet the demand for industry innovation by looking at new ways to approach this complex disease. While past treatments have focused on pathogens, Bayer has developed a new non-antibiotic innovation that focuses instead on the host — specifically, the innate immune system.

Based on Bayer’s long history and expertise in BRD treatment, Zelnate enhances the animal’s natural defense system against infection. Zelnate is the first immunostimulant that:

• Aids in the treatment of BRD associated with Mannheimia haemolytica• Reduces mortality and lung lesions

Zelnate works by jumpstarting the innate immune system in cattle, which has been shown to provide a rapid, potent and broad protective response to infectious agents. Administering Zelnate to cattle at risk of respiratory disease can effectively reduce mortality and lung lesions by enhancing the animal’s own immune system to help fight BRD, potentially reducing the need for antibiotics. Zelnate truly is a novel approach to BRD management—and the story is just beginning.

Innate vs. adaptive immunity

The immune response is commonly thought of as one process, but there are actually two types of immunity: innate and adaptive. The innate immune system is known as the “first line of defense,” because it develops earlier (at birth) and has a faster onset of action than the adaptive immune system—in fact, adaptive immunity is dependent upon an innate immune system response.

While vaccines work with the adaptive immune response to target specific pathogens, immunostimulants trigger the innate immune system in cattle for a rapid and broad response to infection.

Zelnate is different from a vaccine in that it contains no specific antigens, and different from an antibiotic in that it acts on the host rather than the pathogens.

Innate immunity is another approach in infectious disease management.

Linked

hours–days

BroadControls spread

Directs adaptive response

SpecificClears infection

Elicits a memory response

days–weeksONSET OF ACTION*

Innateimmunity

Adaptiveimmunity

Imm

une

resp

onse

*Adapted from Ian Tizard: Veterinary Immuniology 2013.

How Zelnate works

Once administered, Zelnate is engulfed by the animal’s immune cell, where it begins the process of jumpstarting the innate immune system.

The animal’s immune system is now ready to fight infection.

The next generation of immunostimulants

Zelnate™ DNA Immunostimulant is taking immunostimulatory technology to another level with its revolutionary DNA-liposome complex.

Zelnate is made up of a special type of plasmid DNA surrounded by a lipid carrier, or liposome. This DNA has a unique code that mimics infection and jumpstarts the innate immune system in cattle. The liposome protects this DNA as it moves through the immune cell, and has been shown to enhance the uptake of DNA by the immune cell. Finally, the diluent stabilizes the DNA-lipid complex into a ready-to-use solution.

Due to its unique formulation, Zelnate is a stable, effective and safe immunostimulant when used according to the label.

The activated immune cell releases cytokines, which help activate other immune cells and tell them to be prepared for the encounter of pathogens.

Plasmid DNA

Liposome

Diluent

The plasmid DNA PAMP (mixture of CpG motifs and other immuno-stimulatory DNA), is recognized through endosomal TLR9 as well as cytoplasmic DNA recognition pathways. This results in activation of the immune cells.

Immune cell

Within the cell, the Zelnate liposome breaks down, exposing the DNA to endosomal toll-like receptors (TLRs), and delivering the plasmid to the cytosol.

The Zelnate DNA has a pathogen associated molecular pattern, or PAMP, that the animal’s immune cell recognizes as foreign.

Demonstrated efficacy. Real results.

Various studies have been conducted evaluating the efficacy of Zelnate, as measured by:

• Reduction in lung lesions (challenge study)1

• Reduction in mortality (challenge study)2

• Large-scale field comparison to a commonly used antibiotic, Micotil® (tilmicosin Injection)3

Not only did Zelnate significantly reduce lung lesion scores and mortality compared to a negative control group when administered in the face of disease challenge (Fig. 1 & 2), Zelnate also showed similar performance to Micotil when administered to feedlot cattle at medium risk of BRD (Fig. 3).

Fig. 1: Zelnate vs. Control— Reduction of lung lesions1

*Statistically significant reduction (P < 0.05)

*Statistically significant reduction (P < 0.05)

Fig. 2: Zelnate vs. Control— Reduction of mortality2

Fig. 3: Zelnate vs. Micotil—At arrival3

In this study, performance of Zelnate was similar to Micotil

No statistical differences were found between treatment groups across all clinical and performance parameters.

181614121086420

Zelnate ControlAver

age

Lung

Les

ions

(%)

35302520151050

Zelnate Control

Mor

talit

y (%

)

Zelnate vs. Micotil at arrival

Micotil Group

7.65%

17.90%

27.90%

0.44%

3.95%

2.96 lbs

Zelnate Group

13.84%

11.10%

29.10%

0.50%

2.99%

2.91 lbs

Parameter

BRD morbidity

BRD repulls

BRD chronicity

Overall BRD mortality

BRD case-fatality

ADG

Designed with you in mindZelnate™ DNA Immunostimulant was developed not just to work against infection, but also to be easy to implement into routine practices.

Zelnate is available in 5, 10 and 50 dose package sizes to meet the needs of operations of any size. Each box of product comes with a set of mixing instructions and a special color-coded transfer needle, the Zeedle™, to help facilitate ease of mixing and administration. Zelnate is to be administered intramuscularly to cattle at the time of, or within 24 hours after, a perceived stressful event.

There is only one correct way to mix ZelnateIn order for the product to work properly, it is important to follow the instructions closely. The vials themselves were designed with this process in mind, and are numbered 1 through 3 in the order of mixing as well as color-coded to match the Zeedle.

You can view a demonstration video of Zelnate mixing and administration in the video gallery at Zelnate.com.

Bookmark www.Zelnate.com to read up on Zelnate clinical study data, watch informational

videos and more.

For Intramuscular Administration to Cattle

FOR VETERINARY USE ONLY

DNA Immunostimulant

02293

READ IN FULL

DESCRIPTION

ZELNATE™ is a bacterial-produced plasmid DNA with a liposome carrier that stimulates the innate immune system in cattle. The innate immune system has been shown to provide a potent, rapid, nonspecific, protective response to infectious agents, such as those that can lead to Bovine Respiratory Disease (BRD). BRD is a serious condition that commonly causes lung lesions, reduced lung capacity and mortality.

The freeze-dried (desiccate) product is packaged with two different sterile diluents. The First Sterile Rehydrator (vial 1) is used to reconstitute the desiccate cake (vial 2), and then transferred to the Final Sterile Solution (vial 3) to achieve the proper concentration for administration.

INDICATION

ZELNATE™ is indicated for use as an aid in the treatment of Bovine Respiratory Disease due to Mannheimia haemolytica in cattle 4 months of age or older, when administered at the time of, or within 24 hours after, a perceived stressful event.

IMPORTANT STORAGE CONDITIONS

Store Refrigerated 2°C to 8°C (35°F to 46°F) DO NOT FREEZE.

STUDY DATA

In Study A, 3- to 4-month-old steers were randomly allocated to receive either ZELNATE™ or a negative control (N=32 per group). On Day 0, each group of healthy calves was intramuscularly administered their respective treatment and challenged (intratracheally) with Mannheimia haemolytica. Lung lesion scores were obtained on Day 5. ZELNATE™ significantly (p<0.05) reduced lung lesion scores compared to the control group (Figure A).1

In Study B, 3- to 4-month-old steers were randomly allocated to receive either ZELNATE™ or a negative control (N=40 per group). On Day 0, each group was challenged (intratracheally) with Mannheimia haemolytica. Twenty four hours post-challenge (i.e., Day 1), BRD morbidity was observed to be 67.5%. At this time, each group was intramuscularly administered their respective treatment (i.e., in the face of clinical BRD). Lung lesion scores were obtained on Day 5. Among calves that lived until Day 5, ZELNATE™ numerically reduced lung lesion scores compared to the control group (data not shown). The cumulative incidence of death, associated with BRD, was 11.3%. The lung lesion scores among dead calves and those living to Day 5 were observed to be 55.3% and 17.6%, respectively. ZELNATE™ significantly (p<0.05) reduced mortality compared to the control group (Figure B).2

MANUFACTURED BY: Diamond Animal Health, Inc. Des Moines, IA 50237U.S. Veterinary License No. 213Made in U.S.A.

DISTRIBUTED BY: Bayer HealthCare LLC, Animal Health Division P.O. Box 390Shawnee Mission, KS66201 U.S.A.1-800-633-3796

This product is based on technology developed by Juvaris BioTherapeutics and is patent protected. Animal health applications are being exclusively developed by Bayer HealthCare Animal Health and are protected by Bayer patent applications.

©2014 Bayer HealthCare LLC, Animal Health Division, Shawnee Mission, Kansas 66201 U.S.A.

Bayer (reg’d), the Bayer Cross (reg’d) and ZELNATE™ are trademarks of Bayer. 52405B

In conclusion, ZELNATE™, as a stand-alone therapy, has been shown to: 1) significantly reduce lung lesion scores associated with BRD when administered in the face of disease challenge (Study A), and 2) significantly reduce the risk of mortality when administered in the face of clinical BRD (Study B).1Data on file. Bayer HealthCare Animal Health.2Data on file. Bayer HealthCare Animal Health.

Figure A: Average lung lesion scores between calves receiving either ZELNATE™ or a negative control at the same time as an intratracheal Mannheimia haemolytica challenge. Lung lesion scores reflect those observed on Day 5 post-challenge.

Figure B: Cumulative incidence of mortality between calves receiving either ZELNATE™ or a negative control 24 hours after an intratracheal Mannheimia haemolytica challenge. Mortality estimates reflect those observed from the Day of challenge (Day 0) to Day 5 post-challenge.

* = statistically significant reduction (p<0.05)

83944706, R.0 83944722, R.0 83944730, R.0

METHOD OF ADMINISTRATIONInject 2 mL intramuscularly at the time of, or within 24 hours after, a perceived stressful event (for example: weaning, shipping, commingling or adverse environmental conditions). Use entire contents of vial once first opened.

PRECAUTIONDo not administer within 21 days of slaughter.

OTHER INFORMATIONContains no antibiotics and no preservatives. ZELNATE™ has shown no detectable lesions at the site of intramuscular injection.

HOW SUPPLIED Vials of 5, 10 and 50 doses.

2 31Mixing process must be completed in the appropriate order. Transfer needle must be fully inserted to prevent spillage.  

©2015 Bayer HealthCare LLC, Animal Health, Shawnee Mission, Kansas 66201Bayer (reg’d), the Bayer Cross (reg’d), Zeedle™, Zelnate™ and It’s not an antibiotic. It’s not a vaccine. It’s Zelnate.™ are trademarks of Bayer.Micotil is a registered trademark of Eli Lilly and Company. ZNT151085

1Data on file. Bayer HealthCare Animal Health.2Data on file. Bayer HealthCare Animal Health.3Data on file. Bayer HealthCare Animal Health.

Zelnate™ DNA ImmunostimulantNon-antibiotic treatment for BRDZelnate aids in the treatment of BRD due to Mannheimia haemolytica in cattle 4 months of age or older, when administered at the time of, or within 24 hours after, a perceived stressful event.

DNA ImmunostimulantWith a unique DNA-liposome complex that mimics pathogen invasion to help stimulate the innate immune system in cattle, Zelnate enhances an animal’s natural defenses and contains no antibiotics or preservatives.

Research-verifiedZelnate was demonstrated in research studies to significantly reduce lung lesions and mortality (death loss) in the face of clinical BRD due to Mannheimia haemolytica (P < 0.05).

SafeIn field studies, there were no injection site lesions or adverse events observed with the use of Zelnate when used according to the label.

Versatile and practicalZelnate is available in 5, 10 and 50 dose package sizes to meet the needs of operations of any size. With easy-to-follow mixing instructions, Zelnate is simple to implement into existing routine practices.

This product is based on technology developed by Juvaris BioTherapeutics and is patent protected. Animal health applications are being exclusively developed by Bayer Animal Health and are the subject of Bayer patent applications.

For more product information, visit Zelnate.comFor more information on immunology and the innate immune system,

visit www.innateimmunity.bayer.com