Vaccine Safety and (open?) Questions

mostly written in Summer 2021. Partly out of date and wrong. Updates coming.

Rolling publication, new findings and speculations continuously added, since young and healthy people and in some regions even children are not only allowed and motivated but often pressured to take vaccines deemed as safe. Here it is argued that the observed tolerable symptoms do not guarantee safety. Safety is relative: for risk persons of old age, no short term adverse effects is enough for vaccines to be much safer than to catch possibly life-threating Covid. However for young, just knowing there are no serious adverse and diagnoseable effects in the next months, does not mean a vaccine is safe, especially since acute Covid is mild, similar to a common cold or flue, for the young . When its about long-term effects there are unknowns both for SARS-CoV-2 infections and for vaccines. Overall the risk estimation is the protection against adverse events from Covid versus rare and/or speculative adverse effects from vaccination. The possibility of such rare and/or speculative adverse events, is the topic of this page.

In summer 2021, a case of a 18 year old person who died due to thrombosis likely because of vaccination was in the news, which was a push to publish the speculative concerns below. If healthy people are motivated or even pressured to vaccinate, in my opinion, the safety must be ensured and not just be presumed. Often vaccination said to be a considerate and safe action by that the risks and alternatives such as testing come short.

Adenoviruses and how transfected RNA work are currently not main topics of this page and the workings are not discussed with depth. Whether anybody understands all the functions and workings of RNA in depth? RNA can do a lot. RNA is often set equal to messenger RNA (mRNA) which is transcribed from DNA and after a variety of processing steps is translated to proteins. However RNA also has regulatory or enzymatic functions. RNA is used by cells for communication, RNA regulates the translation of mRNA and many cell intern enzymes are RNA. The properties of RNA likely vary with the functions. For example the life time of mRNA produced in the nucleus is usually limited since 1) mRNA is strictly regulated and 2) one break can prevent the translation to the functional protein. RNA with enzymatic functions, such as ribosomes, likely has a longer life-time. Possibly also the RNA of RNA+ viruses including coronaviruses, even though the RNA often is directly translated by ribosomes and thus acts as mRNA.

Information for which of the speculations below the safety is known (both safe and unsafe) is appreciated.

entire page is in work and speculative

Comment and Clarifications in View of Vaccine Mandates

(originally published in the updated section on 9.12. and adapted 19./24.12.21/8.1.22) Some formulations in this chapter are dramatic. // 20.12. changes to more factual formulations in work

• Once to motivate investigations/publications on the cell and tissue tropism and to opt against vaccination of the young until the mechanisms of action are clarified/published.
• To some extent the formulations are/were left dramatic since not only vaccine are recommended but often pushed or even mandated even for the young. Across the world a large share of the people below 30 years is not yet vaccinated and additionally repeated vaccination - commonly referred as ‘boosters’ - is considered/carried out.

Many mentioned of the speculative even if they should occur are likely rare, possibly 1 in 100 or 1000 or less. Possible adverse effects often are random and depend for example on how accurately the vaccine is administrated to the deltoid muscle and whether a draining lymph or a tiny blood vessel is hit.

Besides possible adverse effects, spike targeting vaccines also have epidemiological risks since the outer part of spike mutates frequently is a determinant for the tropism. The frequent mutations make escape forms likely and many mutations can change the tropism. A change in tropism can change the disease pattern - positive and negative. It is not obvious whether anti-spike immunizing those not at risk has advantages on virus evolution. From an individual perspective, it is a weighting of possible adverse effects versus the effects on SARS-2 infections/protection provided (both short-term and long-term).

The speculative adverse effects below are most relevant for children and/or repeated vaccination.

Transparency and Democracy

For democracy transparent and honest information is key. Democracy and a state were everybody is equal before law in agreement with the human rights, may not be possible without transparency. The longer transparency and equality before law are lost, to harder it is to reintroduce them.

Factual and transparent information

• on the different vaccine efficacies (effects on testing positive, on transmission, on hospitalization rates, …)
• on adverse effects and the mechanisms of action.
• on the reasoning behind measures - whether necessary for epidemiological reasons or whether put/left in place for other purposes for example as ‘backdoor’ vaccine mandates (some notes on vaccines mandates in Individual Measures).

Transparency of adverse Effects

If it would known that there are previously unknown/unpublished adverse events, in my opinion the most important is to go transparently public.

• A fond for the affected could be founded. // Founding should be possible - on option is (direct or even indirect) profits and possibly scaled through an insurance.
• Trying to hide possible adverse effect could have high costs both within and between societies and countries - and the world. To costs likely scale with time.
• Supervision and if necessary treatments and other precautions measures could be initiated.

• Summary
• Recent Updates
• Introduction
• Why Symptom Surveillance is often Not enough for Safety
  • The Setting Vaccine Trials were developed
  • Symptom Surveillance is Enough If
  • Symptom Surveillance is NOT Enough If
  • Covid Vaccine Trials
• Kinetics for the Vaccines
  • Introducing Kinetics
  • Motivation to consider the Kinetics
  • Kinetics of mRNA Vaccines
  • Kinetics of Adenovirus Vaccines
• Appendix
  • TBEV Infections

Summary

Surveillance of symptoms is often enough for attenuated live pathogen vaccines since it is known what to except: the possibly severe disease intended to prevent. When the symptoms are tolerable and mild, the (severe) disease is not caused and so the controlled infection by vaccination is safer than the natural infection.

Surveillance of symptoms is not necessarily enough to ensure the safety of other vaccines technologies. Whether tolerable symptoms predict vaccine safety, depends on the technology, the exact formulation and mode of action of a vaccine. Examples where symptom watching is not enough:

• Pathogen causing subtle and/or long lasting infections. In this case to ensure the safety of a live vaccines is not straight forward. E.g. an AIDS vaccine based on the wild type AIDS virus will pass a short term tolerable symptom test and antibodies will be detected. => the kinetics of the pathogen is needed to ensure watching is done over the entire period during which adverse effects can occur.
• For vaccines with adjuvants, safety depends both on the antigens inoculated and the adjuvant. While long-term or subtle adverse effects for protein antigens are unlikely or can be estimated, adjuvants can be anything and possibly reside in the body for decades. => The safety of the adjuvants needs to be ensured.
• Transfected RNA (‘mRNA’ vaccines) may enter arbitrary tissues and cells: Transfection of the wrong cells such as long-lived neurones, stem cells or immune cells can have bad and long lasting effects. Upon transfection different things can happen e.g. cell death can be caused. => For mRNA vaccines it is mandatory to know the tissue and cell kinetics and the exact sequence and nucleoside modifications.
• For adenovirus based vaccines the adenovirus species and its characterization is needed e.g. how they distribute, which cells they attach or infect and the clearance kinetics.
  • Haemagglutination is observed for many adenoviruses, which is possibly the cause of the observed thrombosis events. Which could be prevented e.g. by dosage or administration adaption (e.g. sprayed to the respiratory tract)

    Sprayed vaccines would induce an airway local immunity which unlike systemic immunity provides a good protection against mild disease and transmission.

  • Some adenoviruses have a broad cell tropism. When infecting replication capable cells, adenovirus could in theory increase the cancer risk.

In conclusion, the safety of vaccines can only be ensured by symptoms if a thorough understanding of their behavior in the body is known.

To my knowledge, to behavior of the ‘mRNA’ vaccines and the adeno with spikes vaccines in the body is not published detailed enough for the scientific community to estimate adverse effects.

In software, open source often yields quality improvements. Most successful software at least started open source. Until the 80’s (= before sophisticated compilers and performant mid and high level languages), most software was open source.

Recent Updates

• 23.7.: Extended list of speculative adverse effects:
  • Intramuscular administrated Adenovirus vaccine may increase the cancer risk (depends on the adenovirus strain, mainly whether they enter replication capable cells).

Introduction

There are different definitions of immunisation and vaccination around. Here a general definition is used: Immunisation prepares the immune system to something and thereby protects against a disease. Vaccination teaches the immune system to recognize something.

Why Symptom Surveillance is often Not enough for Safety

The Setting Vaccine Trials were developed

The first vaccines were based on live pathogens (and nearly all of the most successful vaccines still are). First related life-forms providing cross immunity were used and later also the same pathogen but attenuated (Vaccine history). For such vaccines the main concern is to cause the disease intended to immunize against is caused, this happens from time to time. Many (but not all) infections cause immediate symptoms. For most infections symptoms are a good indication how much damage an infection causes and as long as the symptoms are few, serious damage is unlikely. Thus for live pathogen vaccines, it is usually enough to watch for symptoms and detect whether the disease is prevented or at least attenuated enough.

Later on one started to use adjuvants (substances increasing the immune response). If these substances remain long-term in the body or the effects are diffuse and hard to diagnose symptom watching is not enough.

An example, though not in vaccination, but in medications is mercury. Symptom tests were and are common practice for medications. Mercury once passed such symptom tests (its kinetics and behavior within the body were unknown) and was used as medication. Since quite some ago it became known, that mercury can cause subtle damages and enriches within the body it is not used anymore.

Symptom Surveillance is Enough If

Symptom surveillance is enough if one knows what to except including possible adverse effects can be predicted. All the following points should be true:

• The pathogens or substances in question cause immediate adverse effects. Many pathogens of acute diseases don’t stay latent or in equilibrium in the human body but they replicate and thereby their number growths until the immune system controls and reduces them.
• The kinetics of the medication is known:
  • The distribution of the medication within the body is known.
  • It is known how, how fast and the which products the medication in question is metabolized.
  • It is known that the medication and its metabolites are cleared during the surveillance period.

Symptom Surveillance is NOT Enough If

Symptom surveillance is not enough if

• No clear Diagnosis: Substances which cause unknown or subtle and hard to diagnose damage or symptoms. Examples:
  • MDMA (ecstasy) can damage neurones in the brain and cause a slight loss in mental performance. Such subtle effects are hard to detect and not detected in simple symptom tests.
  • Diagnosis of an immune disorder often requires years of careful investigations.
• No favorable Kinetics: The kinetics is either not favorable or entirely unknown. With unknown kinetics the surveillance period needs to be set to lifetime to exclude unwanted effects. Examples:
  • Even tough low doses of mercury pass a symptom test, it enriches in the human body and can be neurotoxic. The latter is known for mercury therefore it is not used anymore as medicine (it was not used for vaccines but for other medications).
• Unfavorable/unknown kinetics combined with unclear diagnosis: The combination of an unknown/unfavorable kinetics with hard to diagnose symptoms makes it especially hard to predict and symptom observations are hard to interpret and causally link.
  • The safety of aluminum as adjuvant is still unclear despite being in use for 90 years. Hard to diagnose symptoms are possible as well as slow clearance. Nevertheless, some risks of adverse effects can worth it to avoid smallpox or polio.
  • Wild type aids viruses pass a short time symptom test. However their kinetics requires life-long surveillance, since they build their genome into long-lived immune cells and therefore AIDS infections are usually life long. Additionally diagnosis of AIDS by symptoms alone is very difficult, since its effect is indirect by increased to susceptibility to secondary infections.

Covid Vaccine Trials

Regarding the current mRNA and vector technologies long term and subtle health hazards are possible too. The published trials only discuss symptoms. Relevant considerations such as the tissue tropism and the exact sequences are neither mentioned in the trials nor by the health authorities.

To me this is strange and not understandable.

Subtle damage (e.g. brain damage or stem cell damage) are mainly relevant when vaccinating children or repeated vaccination.

In my opinion, the rumoured contracts which frees vaccines companies of liability should be waved unless the companies go open source with the entire vaccine technology stack such that an independent safety assessment is possible. If the companies don’t want, they can buy insurances. In the case of the ‘mRNA’ vaccines, these are sold with margin large enough that insurances can be paid if the adverse effects are indeed as rare and unlikely as claimed.

Kinetics for the Vaccines

Introducing Kinetics

An important property to estimate possible effects of things is their kinetics.

Kinetics of Things

Kinetics denotes here the temporal and spacial behavior of things i.e. the distribution and clearance paths.

It is a generalization of pharmacokinetics: not just pharmaceutical drugs but any-thing which can distribute in the body such as pathogens including viruses.

Kinetics can also be defined for viruses and is related to the virus tropism: While tropism denotes how virus entities growth, the kinetics of viruses denotes how single viruses move.

The kinetics can be considered for the different compartment of the body.

• Tissue Kinetics: Do the vaccines administrated to the muscles mainly remain there or do they spread out within the body? Which tissues are reached? Is the blood brain barrier crossed and thus the brain or the bone marrow are reached?
• Cell Kinetics: Which cells are infected in certain tissues? Are long lived or replication capable cells infected?
• Within Cell Behavior: Whats the behavior and the kinetics within the cells? Is apoptosis induced, is the cell metabolism altered?

Motivation to consider the Kinetics

Some points relevant for Covid vaccines are:

• How long the vaccines reside within the body? Knowing the decay is mandatory to know the timescales of possible effects and thus needed to determine the surveillance period.

  Animal experiments or pathology of deaths close in time to vaccination including RNA sequencing and detailed analysis in whether there are any coronavirus spikes around in the cells and tissues would help to bring clarity.

• Tissues: To which tissues the vaccines are distributed? If the vaccines reside within the deltoid muscle where administrated, possible direct effects are mostly localized there. If they vaccines are distributed systemically effects are not localized and much harder to diagnose.

  Also there tissues like the bone marrow or the brain where mRNA transfection is not wanted.

• Cells: What’s the cell tropism of the vaccines i.e. which cells they preferably attach and enter?

  Most cells are subject to the cell turnover which means that they die and are replaced by new ones. So these cells don’t live throughout ones lifetime but shorter, usually much shorter. E.g. the cells in the respiratory tract epithelium are replaced within weeks. For this reason Covid-19 unlikely causes long lasting adverse effects as long as only the respiratory tract is infected (in rare cases, mostly severe infections and when the immune system is not good, the SARS-2 viruses can spread via the blood to other organs).

  On the other hand it is usually bad if long-lived neurones or stem cells are infected. These cell are usually well protected by the body: deep within tissues or even within the bones. Additionally these cell have their own protection against virus infections.

• Within Cells: What happens upon cell infection/transfection? Is cell death induced? If yes, orderly through apoptosis? Are anti-apoptotic factors expressed? Is the nucleus entered? How long the induced materials reside inside cells (mainly relevant for long lived and replication capable cells)?

Kinetics of mRNA Vaccines

The kinetics is crucial to estimate possible adverse effects of the “mRNA vaccines” since lipid particles in the nanometer scale can enter into arbitrary tissues and cells. Entering well protected tissues e.g. by crossing the blood brain barrier and transfecting stem cells or neurons would be worrisome.

Tissue Kinetics

Inference of Tissue Kinetics by Symptoms

Since no tissue tropism experiments are officially published, the tissue tropism can just be guessed from the symptom surveillance.

• The side effects observed for the Comirnaty vaccine (Pfizer/Biontech) hint a lymphotropism (swollen lymph nodes and herpes zooster)
• Neurotropism (bell’s palsy, headache) for both Moderna and Pfizer/Biontech.
• Tropism for the fertility organ: For the Moderna vaccine there are reports that it is affecting women’s periods.

Absence of symptoms for a certain tropism does not mean a vaccine lacks that tropism or even is safe. Only published tissue tropisms could bring clarity.

Possible Effects in different Tissues

The cell and tissue tropism is crucial to estimate adverse effects. For virus infections it is known that neurotropism, lymphotropism and reproductive system tropism can be dangerous. Possibly too for artificial RNA transfection.

Even if any of the following effects should occur, the probabilities to occur are likely low. But for in the case of mass vaccination (with unclear benefits for the young) even low probabilities are relevant.

The effects are highly speculative. Predictions can only be done when ALL the cells and tissue tropism experiments are published (including experiments and trials from formulations which were not proceeded)!

• Neuro-Tropism: Infections of neuron tissues in the bone marrow or in the brain are main dangers of mumps and polio. Severe effects do not occur in the case of “mRNA” vaccines as the trials and the ongoing supervision show. However a limited death of neurones could occur: Possibly in the range from a sleepless night to a couple or many MDMA trips.

  Bell’s palsy then could be attributed that by chance neurones involved in the facial nerve were knocked off.

  Analyzing competitive athletes (including E-Sports) could elucidate even slight performance losses.

  Even minor brain damage is not wanted for children, adolescents or pregnant women.

  Infections with viruses having a neuro-tropism can be both serious or harmless. Sometimes such infections can cause neurological damage for example severe mumps or polio infections. Some viruses such as flaviviruses can cause virulent infections but can also subtle persistent infections, adverse effects of the latter are unclear.

• Lympho-Tropism: If lymphoid tissues are entered and many lymphocytes die, a weakening of the immune system can occur: For some this may cause herpes zooster which is easy diagnosable from visible changes on the skin for others it may be something else:
  • The susceptibility for other herpes viruses (such as CMV) could increase.* Some cancer cells may remain undetected and cause cancer in the coming months or years.
• Female Reproductive Organs: If cells in the follicles or even oocytes themselves are transfected this can have unwanted effects:

  • the number of primordial follicles (respectively local stem cell populations) could be affected.

    This is highly speculative and even if the case the effects are likely not very relevant for adults. In the unlikely event an effect occurs (e.g. since a blood vessel is hit accidentally), it could be in the order of an unhealthy lifestyle for some years.

    Concerns on ‘mRNA’ vaccination, should be accepted until more is known about the underlying mechanisms and better risk estimates are possible.

  • Other effects are possible too, e.g. ingredients such as the transfected RNA, polyethylen-glycol or the produced spikes may remain in oocytes or close by cells - in theory this could affect embryogenesis.

    If the latter is the case, waiting with pregnancy a few months after vaccination could be adequate.

• Bone Marrow: If the bone marrow is infiltrated, pluripotent stem cells can be altered or knocked off. The stem cell niches in the bone marrow are some of the best protected cells for good reason. In theory messing around with the bone marrow stem cell niches can cause many adverse effects such as increased cancer risk.

Cell Kinetics

The ‘mRNA’ vaccines encapsulate the RNA in in lipid nano-particles. Such particulates can in theory enter arbitrary cells.

• Are stem cell entered?
• Are long live cells entered such as immune memory cell or neurons?

Most viruses infect differentiated cells and those infecting long lived or stem cells can be dangerous. At least some RNA strands encapsulated in lipid particulates are taken up and processed by stem cells too, since cell communication for differentiation relies on lipid encapsulated RNA.

These are fundamental properties mandatory to estimate possible adverse effects. However nearly nothing is linked in the trials and a search (google scholar) yields very few results published.

Within Cell Kinetics

What happens upon cell entry?

• Well sometimes the RNA is translated to proteins, is this always the case? Are the produced spike subject to glycosylation?
• Has the RNA other effects within the cells?
• Is cell death caused and if yes orderly through apoptosis?
• Does the some of the transfected RNA enter the nucleus?

  Often it is presumed not without argumentation - I except it as rare but not impossible.

Kinetics of Adenovirus Vaccines

In comparison to ‘mRNA’ vaccines, for adenovirus vaccines it seems less likely that they enter arbitrary cells and tissues since adenoviruses are bigger than lipid nano particles and need a receptor to enter cells. However

• some adenoviruses strains have a broad cell tropism.
• adenoviruses can influence the cellular metabolism in many ways e.g. they can prevent apoptosis.
• adenoviruses can reside within tissues or within cells for a long time since double stranded DNA is stable.

Natural adenovirus infection are mostly limited to the respiratory tract and not systemic, therefore the observation that these infections are mostly harmless does not transform to the systemic administration of vaccines.

Adenovirus Vaccines Clearance

The adenovirus vaccine induced antibody production increases slowly over the time span of several weeks. This indicates a slow clearance. The adenoviruses can reside dormant within tissues but outside of cells or within cells.

Tissue Kinetics

Which tissues are entered? Which share of the administrated dose remains in the muscle, which share is distributed?

The tissue kinetics together with the cell kinetics can help to predict effects: E.g. when many adenoviruses are released into the blood, by the cell kinetics which predicts attachment to red blood cells, blood clumping can be caused.

Cell Kinetics

Two things can happen upon match with a cell:

• Cell Attachment: adenoviruses just attaches but does not enter.
• Cell Entry adenovirus enters the cells.

Adenovirus Cell Attachment

Many adenoviruses attach to red blood cells and thereby can cause haemagglutination i.e. they act as glue to clump red blood cells.

When the vaccine is now overdosed and/or not accurately administrated into the muscle, a large number of adenoviruses can be released into the bloodstream which may cause the blood cells to clump.

The deaths of young people observed would agree with the theory of overdosing. In the trials possibly the personal was better able to accurately administer the vaccine exactly into the muscle.

This can be prevented by

• weight adjusted dosage (still risky)
• using a nasal or oral spray formulation as it is done in farming for decades. Nasal administration would also reduce the risk for other side effects. Additionally provide airways local immunity which helps to reduced viral loads early on and not just prevent pneumonia.

Adenovirus Cell Entry

Different adenovirus strains use different cell entry receptors. Some adenoviruses have a very broad cell tropism.

The broad cell tropism of adenoviruses is worrisome due to their within cell behavior. Adverse effects may occur if long lived or replication capable cells are entered.

The modified adenoviruses used in the vaccines seem to enter mainly myeloid immune cells [to confirm and cite]. If the myeloid are terminally differentiated the cell would not be replication capable and the risk for long-term adverse effects would be greatly reduced [to check and cite].

Within Cell Behavior

Adenoviruses vaccines used adenoviruses rendered replication incapable but apart from this the adenoviruses are similar to their wild type counterparts. As such they can do a lot within cells:

• Enter the cell nucleus. The cell nucleus is the core part of the cell for long lived or replication capable cells this could have adverse effects.
• Alter the cells metabolism in various ways: One thing they do is to produce proteins including the coronavirus spike. Additionally they produce also anti apoptotic substances which is mainly a problem in replication capable cells since the cancer risk could increase.
• Reside dormant within cells for a long time.

Appendix

TBEV Infections

Coincidentally when thinking about the above kinetics in early summer 2021, I didn’t pay attention to ticks, caught one and likely also caught tick-borne encephalitis virus (TBEV). Stupidly didn’t screen for ticks afterwards and realized the tick late, which increases the chance for the transmission tick borne pathogens (Borrelia are unlikely due to symptoms and due to 2x200mg doxycycline post-exposure prophylaxis). The initial illness was very mild which was followed by a regular but slight back pain for a couple of months which more and more faded - so I seem to have been lucky and come through without sequela.

There are vaccines against TBEV which protect mice against deadly disease and produce IgG antibodies in humans, but the effects (positive or negative e.g. ADE is a risk for flaviviruses) of these vaccines (all inactivated viruses with adjuvants) on subtle but possibly persistent infections are to my knowledge unknown. Ideally there would be a safe vaccine mimicking natural infections. Because 1) wild type infections reliably protect against subsequent infections; however 2) wild type infections have risks associated both short-term and long-term. TBEV protection is useful if one loves to move through nature.

The above example of TBEV, is to emphasize that quite common viral infections can be much much more risky than ‘mRNA’ vaccination. TBEV can infect both the CNS and the bone marrow and unlike ‘mRNA’ vaccines TBEV can cause life-long persistent infections. This relativizes the risks and helps factual discussions about the tropism of vaccines.

• No point in worrying about past Covid vaccination. Careful weighting the risk versus the benefits for future ones - regardless whether 1st, 2nd, 3rd, 4rd, … .
• TBEV cases are few, so when 1 in 10 gets hit baldy the absolute numbers are still low. Vaccination is done for millions and even repeatedly. When 1 in 1000 shots causes adverse effects, the risk is low on a individual basis, however the overall numbers would be high.