What is ZyCoV-D®?
ZyCoV-D® is a DNA based vaccine for prevention of COVID-19. It comprises of a DNA plasmid vector carrying full length spike (S) gene region expressing SARS-CoV-2 spike (S) protein along with gene coding for signal peptide. The spike gene region was selected from submitted Wuhan Hu-1 isolate sequence. The S protein of the virus includes the receptor binding domain (RBD), responsible for binding to the human angiotensin converting enzyme-2 (ACE-2) receptor, which mediates the entry of virus inside the cell.
ZyCoV-D® is approved for restricted use in emergency situation vaccine that may prevent COVID-19 disease in individuals 12 years of age and older.
ZyCoV-D® uses which vaccine platform?
ZyCoV-D® is a plasmid DNA based vaccine for prevention of COVID-19.
What are the active drug substances present in ZyCoV-D®?
Each 0.1 mL contains:
1 mg of DNA plasmid construct with spike protein gene region from SARS-CoV-2 virus 1.0 mg, produced in E.coli
Does ZyCoV-D® contain any preservative or excipient?
ZyCoV-D® vaccine contains purified concentrated DNA formulated in Phosphate buffered saline having no preservative
What is the pH of ZyCoV-D® product preparation?
The pH for ZyCoV-D® product preparation is around 7.0.
What is the level of purity of ZyCoV-D® drug product?
The product is highly purified as per GMP requirement
Is ZyCoV-D® a WHO-recommended product?
No not currently
ZyCoV-D® has been granted for EUA in India, however we have future plans for getting the product WHO EUL
Why one would chose ZyCoV-D®?
ZyCoV-D® is based on a novel pDNA platform which belongs to third generation of vaccine.
Has proven efficacy of 66.6% against symptomatic COVID 19
In clinical trials, ZyCoV-D® Vaccine has been shown to prevent COVID-19 disease following 3 doses of 2mg each given 28 days apart. The duration of protection against COVID-19 disease is currently unknown.
Has proven safety profile
Has to be given intradermally by a using a needle free injector system
What is a pDNA?
A plasmid is a small, circular, double-stranded DNA molecule that is distinct from a cell’s chromosomal DNA.
The plasmid construct of ZyCoV-D® carries the spike-S gene of SARS-CoV-2. This pDNA enters host cells, where it remains in the nucleus as an episome; without getting integrated into the host cell DNA. The Plasmid DNA expresses the mRNA, which uses cell machinery to express spike antigen
How is the pDNA present in ZyCoV-D® is synthesized?
The DNA vaccine candidate against SARS-CoV-2 is comprised of a DNA plasmid Vector pVAX1 carrying spike-S protein of SARS-CoV-2. Plasmid DNA carrying Spike gene was transformed into E coli cells to select the desired clone with plasmid carrying spike gene . The E coli carrying the plasmid DNA was further propagated for large scale production.
What are the major differences between mRNA and pDNA vaccines?
Both DNA and mRNA platform represents the latest generation of vaccines based on nucleic acid technology. The difference between DNA and mRNA technology is that, DNA molecule coding for target antigen need to reach nucleas where transcription leads to mRNA synthesis using host cell machinery and further protein synthesis happens in cell cytoplasm through translation. On the other hand, the mRNA vaccine does not need to reach the cell nucleus like the DNA ones.
DNA Vaccines are stable at 2-8C and at room temperature, whereas the mRNA vaccines requires ultralow temperatures of -20C and -70C
For more details please refer to section on vaccine basics and media center
What are the therapeutic indications of ZyCoV-D®?
ZyCoV-D® is indicated for active immunisation of individuals ≥12 years old for the prevention of coronavirus disease 2019 (COVID-19).
Does the pDNA present in ZyCoV-D® gets integrated into human genome?
The plasmid construct of ZyCoV-D® carrying the carrying spike-S gene of interest enters host cells, where it remains in the nucleus as an episome; without getting integrated into the host cell DNA.
Current nonclinical and clinical databases support that prior concerns about integration, autoimmunity and immunopathology have not been borne out
What is the mechanism of action of ZyCoV-D®?
The plasmid construct of ZyCoV-D® carrying the carrying spike-S gene of interest enters host cells, where it remains in the nucleus as an episome; without getting integrated into the host cell DNA.
Thus using the host cell’s protein translation machinery, the inserted cloned gene in the episome will direct the synthesis of the antigen it encodes. The protein produced by plasmid-transfected cells is likely to be expressed within the cell and folded in its native conformation.
Further the signal peptide prompts cells to translocate the protein, usually to the cellular membrane. The antigen is recognized by antigen presenting cells (APCs) and further induces antibodies including neutralizing antibodies and cellular immune response through major histocompatibility complex (MHC).
Does ZyCoV-D® bind to nCoV virus? How does it act against corona virus?
The mode of action of ZyCoV-D® is to trigger immune response by trigerring both humoral and cell mediated immunity. This is mediated by generation of various interferons and antibodies that would prevent COVID infection by blocking virus entry into cell and also destroys cells already infected with SARS-CoV-2.
ZyCoV-D® does not bind with nCoV virus itself.
What is the route and dose of administration of ZyCoV-D®?
ZyCoV-D® vaccination schedule consists of 3 separate doses to be given at an interval of 28 days each (day 0, day 28 and day 56).
Each dose consists of two shots of 0.1ml each given by needle free injector (Pharmajet Tropis device) via intradermal route at two separate sites (preferably deltoid region of both the arms).
Can ZyCoV-D® be injected in to the blood vessel?
No, it has to be given intradermally only, by using a needle free injector system (pharmajet tropis device)
What is pharmajet tropis?
It is a needle free injector device (Pharmajet Tropis device), for administering ZyCoV-D® via intradermal route at two separate sites.
Is it necessary to give ZyCoV-D® with pharmajet?
ZyCoV-D® has to be given by intradermal route, using needle free injector (Pharmajet Tropis device) only. The step by step guidance on method of administration using Pharmajet Tropis device is available in the medication Guide for Method of Administration
Can ZyCoV-D® be given by a regular injections and syringe?
No it should not be administered by regular injections and syringe.
ZyCoV-D® has to be given by intradermal route only using needle free injector (Pharmajet Tropis device).
How does pharmajet device work?
The spring powered Injector delivers the vaccine by means of a narrow, precise fluid stream, which penetrates the skin in about 1/10 of a second and gets the vaccine where it needs to be. No external power source is required.
What does the needle-free injection feel like ?
Not unlike traditional injections, individuals will respond differently to the needle-free injection. Some feel nothing, while others have reported feeling the pressure of the injection or a snap like a rubber band when the injection is administered.
How many shots can be given with one device?
Pharmajet- tropis device is recommended for 20000 shots (10000 doses) of ZyCoV-D® vaccine. It’s ISO certified & single device is tested for more than 30000 shots.
What are the benefits of needle-free injection system- pharmajet tropis?
Needle-free technology significantly reduces patient fear and anxiety associated with getting a needle injection. It eliminates needle stick injuries to healthcare workers, greatly reduces the need for sharps disposal, eliminates needle reuse and the possibility of cross-contamination
How to ascertain that one pharmajet device has delivered 20000 shots and till how many shots the device could be function worthy?
There is no tracker in device to know the number of shots that have been delivered. This device is mechanical pressure device and this device either works or it will not work (there is no partial performance of device after 20000 shots) device is tested for more than 30000 shots & is ISO certified. We strongly recommend to use the device for 20000 shots only.
Replacement and repair of device in case of any technical issue?
Zydus will take the responsibility to replace the device asap if there is any technical issue with the device. Device damaged due to mishandling will not be replaced.
Inoculation accuracy, spillage of dose – is there any issue?
The device is tested and needle free syringe ensures the accuracy of dose with no spillage. Millions of doses have been given world-wide through such devices.
Dataor experience – pain/reaction at site of injection, contamination?
ZyCoV-D® Interim study demonstrates 0.66% of pain at Injection site (Solicited response) after first dose, Please refer to the ZyCoV-D® Pack insert for more information. There was no contamination reported.
If there is wet patch after the dose, do we need to re vaccinate?
No, tropis ensures the right dose administration if right admistration technique is followed. for any wet patch seen, re-dosing is not recommended.
How can we clean the device?
You can use the alcohol swab to wipe the device. Device doesn’t come in contact with vaccine directly
Storage condition for device? As India has extreme temperature condition
Device can be kept at room temperature. Follow the storage process and guideline for any other medical device as per local recommendation.
Sterilisation process of vial top – one more step, which material should be used for sterilisation?
Sterilisation process should be as per MOHFW COVID 19 vaccine guideline if required.
Would there be any impact of alcohol usage ( while wiping device/ vial top) on Vaccine efficacy?
No study has been conducted regarding impact of alcohol wipe for sterilisation on ZyCoV-D® Multi-dose vaccine vial tip. We recommend to use MOHFW Covid-19 Vaccine operational guidelines.
For how many days, multi dose vial of ZyCoV-D® can be used?
ZyCoV-D® vial once opened (multi-dose vials) should be used as soon as practically possible and certainly within 14 days when kept between +2ºC and +8ºC. All opened Multidose vials of ZyCoV-D® should be discarded at the end of immunization session or within 14 days whichever comes first. Please refer to ZyCoV-D® Pack Insert for more information
How to treat discarded syringe?
Kindly follow the MOHFW Covid-19 operational guidelines. As ZyCoV-D® is administered through a needle free injection System, the hub-cutter process is not required. NFIS syringe used can be directly put in the red bag. Do not put the syringes on the table or on a tray after use.
Route of administration – ID or ID With Pharmajet device?
Each dose consists of two shots of 0.1ml each given by needle free injector (Pharmajet Tropis device) via intradermal route at two separate sites (preferably deltoid region of both the arms).
What if the electricity issue & Cold-chain of 2-8 degree storage is not maintained?
It is recommended to store ZyCoV-D® at 2° to 8°C. However our developmental studies have shown that it is stable for upto 3 month at 25 deg C.
Is the vaccine freeze sensitive? Can we freeze it?
In case of unexpected freezing of vaccine at 2-8ºC storage, it can be administered after thawing.
Is there any VVM on vial?
No as per MOHFW Covid-19 operational guidelines 7.2.1, there will be no VVM on the vial. Cold chain management for the all vaccine is the prime importance by the vaccination site supervisor.
Two shots – is this scientific or technical limitation of device?
ZyCoV-D® has to be given by intradermal route only using needle free injector (pharmajet tropis device). pharmajet tropis device has the limitation to administer 0.1ml ID dose with this device.
Can alternative route of ID needle be used?
No, ZyCoV-D® has to be given by intradermal route only using needle free injector (pharmajet tropis device).
Is there any study on cost of device versus standard ID route?
No, there is no study conducted till date. But feasibility study conducted on NFIS device in IPV in pakistan show better acceptability of NFIS among care givers with 0% vaccine loss.
Can adaptor be re-used for multiple vials?
1 filling adaptor is recommended to be used for only 1 multi-dose vial for 10 dose (20 shots) of ZyCoV-D®. There are chances of contamination during the process of re-use. Therefore, it is not recommended to use the filling adaptor for more than one multi-dose vials.
Will there be any issue of in filling syringe if vacuum is developed after few dosage.
As per process the vial has to be inverted to drive the vaccine in syringe. Chances of vacuum to be developed through filling adaptor in syringe are negligible. If vacuum is developed re-do the entire process.
Who should not get ZyCoV-D® vaccine?
You should not get ZyCoV-D® vaccine if you:
- Had a severe allergic reaction after a previous dose of this vaccine
- Had a severe allergic reaction to any ingredient of this vaccine
- Had a severe allergic reaction to any other vaccine
For more details please refer to the fact sheet of ZyCoV-D®
Can we get pharmajet device demo usage & medication guide material for self training.
1. Yes, you can connect with the vaccine state immunisation officer/ vaccination
site supervisor. Training Kit’s is available with vaccination site supervisor/ state
immunisation officer on pharmajet device. For any query on vaccine follow Pack
Insert.
OR
2. Every Pack of ZyCoV-D® has the printed medication guide.
3. Access QR code printed on ZyCoV-D® Pack/ Pack insert /Medication guide to view
the medication guide for admistration of ZyCoV-D® video in english & hindi.
OR
4. Visit website www.zycovd.co.in for more information & connect for any other
query.
How is ZyCoV-D® stored?
Store at 2° to 8°C. Do Not Freeze
Multidose Vials: To be used within 14 days of opening
What is the shelf-life of ZyCoV-D® product?
The shelf life of vaccine is 6 months when stored at 2° to 8°C.
Once opened, multi-dose vials should be used as soon as practically possible and within 14 days when kept between +2ºC and +8ºC. All opened multidose vials of ZyCoV-D® should be discarded at the end
of immunization session or within 14 days whichever comes first.
The expiry date of vaccine is indicated on the label and packaging.
Can ZyCoV-D® product be stored at room temperature?
It is recommended to store ZyCoV-D® at 2° to 8°C.
However our developmental studies have shown that it is stable upto 3 month at 25 deg C.
Can ZyCoV-D® product be stored under frozen condition?
It is recommended to store the vaccine at 2° to 8°C.
Do Not Freeze
In case of unexpected freezing of vaccine at 2-8ºC storage, it can be administered after thawing.
How many formulations with different strength of doses are available?
Vaccine is formulated in Phosphate Buffered Saline and the dose strength is 1mg per 0.1 mL
Available in presentation of 0.5 ml vial or 2 ml vial.
ZyCoV-D® is supplied in a USP type-1 tubular glass vial.
Can ZyCoV-D® be used for multi-dosing?
Yes, ZyCoV-D® is available in 2 ml vials that can be used for multidosing for different individuals
To be used within 14 days of opening
What is the dosing regimen of ZyCoV-D®?
ZyCoV-D® vaccination schedule consists of 3 separate doses to be given at an interval of 28 days each (day 0, day 28 and day 56).
What is the efficacy of ZyCoV-D® vaccine?
ZyCoV-D® vaccine has shown efficacy of 66.6% in interim analysis.
Does ZyCoV-D® vaccine neutralize delta variant and other nCoV virus variants?
In clinical trials, ZyCoV-D® Vaccine has been shown to prevent COVID-19 disease following 3 doses of 2mg each given 28 days apart.
The phase 3 clinical trial of ZyCoV-D® that had been conducted during the peak of second deadly wave of pandemic that was attributed to delta variant for evaluating the efficacy of vaccine.
ZyCoV-D® has shown an overall efficacy of 66.6% in this clinical trial against symptomatic COVID-19 and an efficacy of 100% agasint moderate COVID-19 infection.
However specific neutralization assays against various variant needs to be conducted.
What was the immunogenicity data from phase 3 clinical trial of ZyCoV-D®?
The interim immunogenicity titres for both the adults and adolescents are as under:
How does the activity (immunogenicity) of ZyCoV-D® measured?
For evaluating immunogenicity following assays were conducted:
IgG ELISA against spike protein (S1 antigen ELISA)
Wild type virus neutralization assay (PRNT50)
Cellular response by INF gamma secreting cells (Ellispot)
Would an individual be protected against COVID-19 if that individual could not complete all three doses of ZyCoV-D®?
If an individual receives one dose of ZyCoV-D® vaccine, then the 2nd / 3rd dose should be administered 28 days after the previous dose. It is imperative that an individual completes all 3 doses of ZyCoV-D® vaccine.
At present, there is no data on efficacy of vaccine with 1/2 doses (2mg) of vaccine till date
As per interim analysis, we have efficacy data after day 28 after the third dose.
Can ZyCoV-D® be administered to pregnant females?
The safety and efficacy of ZyCoV-D® in pregnancy has not been established
Can ZyCoV-D® be administered to breastfeeding females?
The safety and efficacy of ZyCoV-D® in lactating females has not been established.
Can ZyCoV-D® be prescribed for infants or children?
Efficacy and safety data are currently limited in adolescents aged 12 to <18 years. No dosage adjustment is required in adolescents 12 to <18 years of age.
The safety and efficacy of ZyCoV-D® in children (aged <12 years old) has not yet been established.
Has ZyCoV-D® been tested in Geriatric population?
Yes it has been tested. Efficacy and safety data are currently limited in individuals ≥ 60 years of age. No dosage adjustment is required in elderly individuals ≥ 60 years of age.
Can ZyCoV-D® be prescribed for immune-compromised individuals including HIV/AIDS?
It is not known whether individuals with impaired immune responsiveness, including individuals receiving immunosuppressant therapy, will elicit the same response as immunocompetent individuals to the vaccine regimen.
Should ZyCoV-D® be administered to person who has been exposed to COVID?
Yes it may be given to people who have recovered from COVID-19, as per GOI guidelines
Who should not get ZyCoV-D® vaccine?
Following individuals should not get ZyCoV-D® Vaccine:
• If the individual had a severe allergic reaction after a previous dose of this vaccine
• If the individual had a severe allergic reaction to any ingredient of this vaccine
• If the individual had a severe allergic reaction to any other vaccine
Can ZyCoV-D® vaccine cause anaphylactic shock?
Yes it may cause anaphylactic shock, as with all injectable vaccines, however no case has been reported in clinical trials till date.
Can ZyCoV-D® product be administered with any other vaccine?
No interaction studies have been performed.
Concomitant administration of ZyCoV-D® with other vaccines has not been studied.
Is it safe to administer ZyCoV-D® at a dose higher than the recommended dose?
Experience of overdose is limited. There is no specific treatment for an overdose with ZyCoV-D®.
In the event of an overdose, the individual should be monitored and provided with symptomatic treatment as appropriate.
Is there any drug-drug interactions observed between ZyCoV-D® and other antibodies, vaccines, drugs etc?
No interaction studies have been performed.
Concomitant administration of ZyCoV-D® with other vaccines has not been studied
Does ZyCoV-D® vaccine lead to impairment of the ability to drive a vehicle?
ZyCoV-D® has no or negligible influence on the ability to drive the vehicle.
Does ZyCoV-D® vaccine lead to impairment of the ability to operate machines?
ZyCoV-D® has no or negligible influence on the ability to operate machines.
What are adverse events observed after taking ZyCoV-D®?
Most commonly observed adverse events are:
• Injection site redness
• Injection site pain
• Injection site itching
• Injection site swelling
• Fever
• Muscle Pain
• Headache
• Nausea
• Fatigue / Tiredness
• Diarrhea
Most of the adverse events were mild or moderate in severity.
These may not be all the possible side effects of ZyCoV-D® Vaccine. Serious and unexpected side effects may occur.
Does skin lesion occur at the site of ZyCoV-D® vaccine?
Yes it can cause redness, swelling at the site of administration, however this susides quickly with or without symptomatic treatment
How to report adverse event?
To report adverse events, call toll free on 1800 419 1141 or visit www.zyduscadila.com
Can I contract COVID-19 by taking ZyCoV-D® vaccine?
No. ZyCoV-D® Vaccine does not contain SARS-CoV-2 virus and cannot give you COVID-19 infection.
Can ZyCoV-D® product be mixed with saline or dextrose solution for administration?
No it should not be mixed with saline or dextrose solution.
Please follow the medication guide for more details about administration of vaccine
Is ZyCoV-D® drug product required to be reconstituted before administration?
No, ZyCoV-D® is a sterile preservative free clear colorless liquid solution for intradermal injection.
Is ZyCoV-D® drug product presented in ready-to-use form?
Yes, ZyCoV-D® is a sterile preservative free clear colorless liquid solution for intradermal injection.
Is ZyCoV-D® available in countries other than India?
At present, it has been granted EUA only for use in India.
How can the authenticity of ZyCoV-D® be verified?
With increasing instances of counterfeit products in the market it has become important to ensure that a 100% genuine product is available to patients. So to safeguard patients against the counterfeit drugs Zydus’ has developed and launched a new tech enabled initiative known as Zydus Verify.
Zydus Verify can help in verifying the authenticity of ZyCoV-D® vaccine.
How does Zydus Verify work?
Each pack has a concealed secret code which comes with a scratchable surface
The individual who buys the pack, scratches the surface and finds a code
Individual downloads Zydus Verify App from Google Play store and Apple Store or visit the website www.zydusverify.com and enters the code on the pack
The App connects the code and flashes the brand name verifying a genuine purchase.