Biodistribution of Pfizer Covid-19 Vaccine
When a substance is injected into the body, tracking where it goes- its biodistribution is important to know.
Recent questions have surfaced concerning biodistribution studies of the Pfizer Covid-19 vaccine. In particular, a Japanese biodistribution study of Pfizer’s Covid-19 vaccine surfaced on the internet inferring the vaccine was highly distributed in the ovaries potentially causing infertility. This is in contrast to current thinking the mRNA vaccine is quickly broken down at its site of injection in the arm implying no distribution to other organs.
What did the initial Pfizer biodistribution studies show? What is the length of time the vaccine exists in the body after vaccination? In what organs can you find the vaccine? Why are these questions surfacing now? What is the clinical outcome?
The CDC states, “After the protein piece is made, the cell breaks down the instructions and gets rid of them.”** However, a Japanese document of the Pfizer vaccine data showed biodistribution beyond the local injection site, with distribution highest in the ovaries at 48 hours. Why the confusion? What is the real truth?
I thought this would be an easy blog to write, cut and dry. Find the original research and move on! Not so. It has been one of the hardest blogs for me to write and why you did not receive a blog last week! My intent is to bring you facts, not conjecture or opinion. I highlighted important points for easier reading.
After spending 20 hours of research, I found there are no animal biodistribution studies of mRNA vaccines done by Pfizer, Moderna, or J and J published on an internet search.
Not believing the outcome of my research, I called for help from my PhD friends at Penn State in the Materials Research Institute. They confirmed what I had found. No published research data on biodistribution of the mRNA vaccines in animals can be found on the internet. This does not mean the animal studies were not done. It only means the studies are not available on an internet search.
In response to information not being available on the internet, a Citizen petition to the FDA was filed by 27 prominent health experts and scientists on June 1, 2021, requesting proper pharmacokinetic and biodistribution safety studies be revealed or conducted by the vaccine manufacturers. The petition and its supporting documents can be downloaded from the FDA website here: https://www.regulations.gov/docket/FDA-2021-P-0521/document
However, information regarding biodistribution of the Pfizer vaccine in animal studies was referenced by the European Medicine Agency’s (EMA) review of Pfizer’s mRNA vaccine data sent to them by Pfizer. This information is found on the internet leading us to assume, yes, biodistribution studies in animals were conducted by Pfizer. I am giving you the technical version so you can see for yourself the actual data reviewed by EMA. https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf
Most of the studies referenced by EMA are not available on the internet, but can be requested as was done by the Citizens petition.
EMA Reviews Pfizer Covid-19 Vaccine Animal Biodistribution Study Data
The European Medicine Agency (EMA) is an agency of the European Union (EU) in charge of the Evaluation and Supervison of Medicinal Products.
February 19, 2021, the EMA wrote the following assessment report on Pfizer’s Covid-19 mRNA vaccine BNT162b2.*
“Safety pharmacology studies
- No safety pharmacology studies were conducted with BNT162b2.
- The Applicant refers to that as they are not considered necessary according to the WHO guideline (WHO, 2005).
- In addition, no findings on vital organ functions have been recorded in the repeat dose toxicology studies. Thus, the absence of safety pharmacology studies is endorsed by the CHMP, Committee for Medicinal Products for Human Use.
Pharmacokinetics
- No traditional pharmacokinetic or biodistribution studies have been performed with the vaccine candidate BNT162b2.
- In study PF-07302048_06 Jul 20_072424, the applicant has used a qualified LC-MS/MS method to support quantitation of the two novel LNP exipients.
o LNP=LipoNanoParticle which carries the mRNA
o LC-MS/MS is liquid chromatography with tandem mass spectrometry
- The bioanalysis methods appear to be adequate.
When I looked up study PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines) Protocol C4591001, I found no mention of biodistribution, only the following stated on page 72/147:
- 8.5. Pharmacokinetics Pharmacokinetic parameters are not evaluated in this study.
- 8.6. Pharmacodynamics Pharmacodynamic parameters are not evaluated in this study.
- 8.7. Genetics Genetics (specified analyses) are not evaluated in this study.
- 8.8. Biomarkers Biomarkers are not evaluated in this study.”***
However, the EMA referenced study PF-07302048 and its biodistribution results as below:
”Biodistribution of a LNP-formulated luciferase surrogate reporter”:
(Meaning they substituted a luciferine protein in place of the actual mRNA part of the vaccine. Using Luciferine to follow biodistribution of a product is common practice. Technically, it is not following the mRNA vaccine itself but following where the LNP container-luciferine goes as a surrogate to understanding where the mRNA may go. This is important to understand.)
- “To determine the biodistribution of the LNP-formulated modRNA, the applicant did study distribution of the modRNA in two different non-GLP (Good Laboratory Practice) studies, in mice and rats,
o determined the biodistribution of a surrogate luciferase modRNA formulated with a LNP with identical lipid composition used in BNT162b2 (mouse study)
o or the biodistribution of a [3H]-Labelled Lipid Nanoparticle-mRNA Formulation (rat study).
- The mouse study used three female BALB-c mice per group and luciferase protein expression was determined by in vivo bioluminescence readouts using an In Vivo Imaging System (IVIS) following injection of the luciferase substrate luciferine.
- The readouts were performed at 6h, 24h, 48h, 72h, 6d and 9d post IM injection (intended clinical route) in the right and left hind leg with each 1 μg (total of 2μg) of LNP-formulated luciferase RNA.
- In vivo luciferase expression was detected at different timepoints at the injection sites and in the liver region indicating drainage to the liver.
- As expected with an mRNA product, the luciferase expression was transient and decreased over time.
- Luciferase signals at the injection sites, most likely reflecting distribution to the lymph nodes draining the injection sites, peaked 6h post injection with signals of approximately 10 000 times of buffer control animals.
- The signal decreased slowly during the first 72 hours and after 6 and 9 days the signals were further weakened to approximately levels of 18 and 7 times the signals obtained from animals injected with buffer control.
- The signals from the liver region peaked 6h post injection and decreased to background levels 48h after injection
- The liver expression is also supportive of the data from the rat PK study and the findings in the rat repeat-dose toxicological study showing reversible liver vacuolation and increased GGT levels.
“The biodistribution was also studied in rats using radiolabeled LNP and luciferase modRNA (study 185350).”
- “The radiolabeling data, measuring distribution to blood, plasma and selected tissues, of IM injection of a single dose of 50 μg mRNA over a 48-hour period is considered more sensitive than the bioluminescence method and indicate a broader biodistribution pattern than was observed with bioluminescence.
- Over 48 hours, distribution from the injection site to most tissues occurred, with the majority of tissues exhibiting low levels of radioactivity.
- Radioactivity was detected in most tissues from the first time point (0.25 h) and results support that injections site and the liver are the major sites of distribution.
- The greatest mean concentration was found remaining in the injection site at each time point in both sexes.
- Low levels of radioactivity were detected in most tissues, with the greatest levels in plasma observed 1-4 hours post-dose.
- Over 48 hours, distribution was mainly observed to liver, adrenal glands, spleen and ovaries, with maximum concentrations observed at 8-48 hours post-dose.
- Total recovery (% of injected dose) of radiolabeled LNP+modRNA outside the injection site was greatest in the liver (up to 21.5%) and was much less in spleen (≤1.1%), adrenal glands (≤0.1%) and ovaries (≤0.1%).
- The mean concentrations and tissue distribution pattern were broadly similar between the sexes.
- No evidence of vaccine-related macroscopic or microscopic findings were found in the ovaries in the repeat-dose toxicity studies (Study 38166 and Study 20GR142)
- and no effects on fertility were identified in the DART, Developmental and Reproductive Toxicology, study.”*
The bottom line is mRNA Covid vaccines are still considered experimental by the FDA as research continues to be done. We do not have all the animal or clinical data needed to completely evaluate long term safety of the mRNA vaccines. We won’t know the final answers to many questions concerning the mRNA vaccines until at least 2022 or perhaps longer.
People will continue to gather evidence supporting the vaccine, and people will continue to gather evidence against the vaccine. Ultimately at this juncture, it is a personal decision considering the risk vs. benefit ratio. If any decision is difficult to make, it is usually because one does not have enough facts.
Have an awesome day! Dr. D