COVID-19 Pfizer/BioNTech mRNA Vaccine BNT162b2: toxicolgy and pharmacodynamics

Graham Crawley made this Freedom of Information request to Medicines and Healthcare Products Regulatory Agency

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Dear Medicines and Healthcare Products Regulatory Agency,
Regarding COVID-19 Pfizer/BioNTech mRNA Vaccine BNT162b2 hereinafter called "the vaccine"

Please provide the following information

1. How is the vaccine distributed throughout the body?
2. Which cell types in which tissues do the vaccine lipid nanoparticles transfect?
3. In transfected cells, for how long do the cells synthesise the spike protein and what limits the synthesis?
4. What is the fate of the transfected vaccine mRNA at cell death and cell division?
5. Does the vaccine mRNA, after reverse transcription, integrate into the host cell genome: what studies have been done to address this?
6. Regarding the spike protein:
a) Has the spike protein produced by transfected cells been sequenced and what modifications are there compared to the Wuhan spike protein?
b) Does the spike protein generated by the vaccine comprise both S1 and S2 domains?
c) Does the spike protein generated by the vaccine incorporate the furin cleavage site?
d) As proline or other amino acids have been substituted into the spike protein produced by the vaccine:
i) What are the relative binding affinities of the modified spike protein to the ACE2 receptor compared to the original Wuhan spike protein?
ii) Are the substitutions in the S1 or S2 domains or both domains?
e) have soluble proteins, derived from cleavage of intact spike protein or arising from translation errors, been looked for/detected in the circulation and, if so, what are the biologcal consequences of these proteins?
7. Regarding N-methyl-pseudouridine:
a) how accurately does the N-methyl-pseudouridine base substitute for uridine during translation and what are the consequences of miscoded protein which may result from errors?
b) is the N-methyl-pseudouridine base found in host cell natural mRNA after inoculation?
c) what toxicological studies have been conducted with N-methyl-pseudouridine or a derivative, and what were the results?
8. What toxicological studies have been carried out with lipids ALC-0315 and ALC-0159?
9. The manufacturer has described four identified drug product manufacturing process-related
impurities. What are they?
10. In the final product, what is the % purity of BNT162b2 mRNA based on total synthesised RNA?
11. To evaluate toxicological studies, what are the relative affinities of spike protein produced by transfected cells with human and rat ACE2 receptors?
12. What were the results of the combined fertility and developmental study (including teratogenicity and postnatal investigations) in rats?
13. As the vaccine is more akin to a prodrug generating potentially both membrane bound and soluble spike protein, why have no genotoxicity, including Ames test, and carcinogenicity studies been conducted?

Yours faithfully,

Graham Crawley

MHRA Customer Services, Medicines and Healthcare Products Regulatory Agency

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MHRA Customer Services, Medicines and Healthcare Products Regulatory Agency

Our Ref: FOI 21/715

Dear Graham Crawley,

RE: REQUEST UNDER THE FREEDOM OF INFORMATION ACT 2000

Thank you for your enquiry which we received on 24 June 2021.

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Dear MHRA Customer Services,
Please reply immediately to this request. You should have replied by 23/07/2021

Yours sincerely,

Graham Crawley

MHRA Customer Services, Medicines and Healthcare Products Regulatory Agency

Thank you for your email.  This auto-response is to inform you that your
email has been received and will be reviewed by our Customer Service Team.
We will respond to you as soon as possible. 

 

Please note that we may not respond if your query: 

 

• contains offensive language
• has already been answered in a previous reply to you
• is illegible
• is selling or promoting a product
• is for information only 

 

Medicines and Healthcare products Regulatory Agency
10 South Colonnade, 
Canary Wharf, 
London 
E14 4PU
gov.uk/mhra
Stay connected 
 
For information on how the Agency uses your personal data and your data
protection rights, please see our three centres’ Privacy Notices: MHRA,
CPRD and NIBSC. 

 

The UK has left the EU, and the transition period ends on 31 December
2020. Our [1]guidance and information can be accessed here. 

References

Visible links
1. https://www.gov.uk/government/collection...

MHRA Customer Services, Medicines and Healthcare Products Regulatory Agency

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Dear Mr Crawley,

Thank you for your email.

Please find attached response that was sent on 7 July.

Kind Regards

MHRA Customer Service Centre

Medicines and Healthcare products Regulatory Agency
10 South Colonnade, Canary Wharf, London E14 4PU Telephone 0203 080 6000

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