Public Health

COVID Vaccines’ Biomechanics and Efficacy

While vaccination against COVID confers obvious and substantial benefits in preventing serious illness, booster shots have a complex immunology that means they come with a risk and must be considered with great care. Dr Rochelle Walensky, a physician-scientist who directs the US Centers for Disease Control and Prevention (CDC)  and Dr William Powderly, an infectious diseases physician from Washington State, expressed reservations about the current enthusiasm for Covid vaccination:  “So many of us wanted to be hopeful: this [vaccination] is our ticket out. Now we are done”. Looking back, they say there was “too little caution and too much optimism”. We skated over the possibility of resistant variants. Walensky and Powderley concluded the “the science was grey, not black and white”.

Given that a pandemic threatens unprecedented human and economic destruction, the surprise is that the world hung its hopes on a vaccine designated as experimental.  Lessons learnt over decades of experience with influenza vaccines were of low currency

While all vaccines against COVID shifted the clinical response to infection towards less severe disease, what they were never going to achieve was herd immunity, as seen with, say, measles and poliomyelitis. The immunology of COVID and vaccination against it is quite different to that which applies to those two conditions. Guided — or perhaps misguided is the better word — by experience with polio and measles, where vaccination rates between 85 per cent and 95 per cent led to herd immunity, COVID-related models were developed that suggested vaccination rates could also be calculated to achieve herd immunity. But these models were in error.

The difference between measles and COVID was not understood — and if it was grasped, it was ignored.  Measles is a systemic infection – the virus travels through the blood stream to damage target organs. The measles sufferer demonstrates a vigorous immune response, recruiting an army of cells and molecules to rapidly neutralise the offending virus and kill any infected cell.

Infection by influenza or COVID viruses could not be more different. the COVID-19 virus infects the lining, the  mucosal space, of the respiratory tract. The relationship between the virus and the mucosal immune response, driven by the infection, determines the clinical outcome. The details of the response are complex, so if you will bear with me I will lay out the points in bold and address them in commentary below each.

 

♦ The virus stimulates lymphocytes (B and T cells) that reside in clusters in the wall of the pharynx and the gut. These differ from those generated by measles antigens in the lymphoid tissue elsewhere in the body.

The body mounts an inflammatory reaction to virus in the blood to maintain sterility, but that is not possible in the pharynx and gut because the mucous membranes are bathed in a myriad of bacteria and viruses known as the microbiome.

In this circumstance an inflammatory response such as found with T and B cells in the body more generally, would destroy the respiratory tract mucosa. So, the dominant mucosal antibody – IgA – cannot trigger the extensive inflammatory response seen in polio or measles which IgG  prompts.  Instead, a carpet of dendritic cells in the mucosa processes the virus before migrating to regional lymphoid tissue. There they induce an active population of suppressor T cells, or T reg cells.

The COVID virus stimulates a second set of T cells within the mucosal lymphoid tissue, which are responsible for co-ordinating protection against the virus. Protection is achieved by these T cells, through the creation of an anti-viral environment within the mucosa, made up of molecules (known as cytokines) and activated cells. This collection of molecules and cells (known as the innate immune system) indiscriminately kills whatever it is close to. Think here of an exploding hand grenade. Defects in this process have been linked to severe COVID disease.  

 

The mucosal compartment (COVID) and systemic compartment (measles and polio) are separate systems.

In the mucosal compartment the local immune response to COVID is highly efficient, restricting the virus to the airways. Whether infection is asymptomatic or the cause of local symptoms, such as cough, depends on the efficiency of the mucosal immune response: if T cell function is delayed or inefficient (as it is in older subjects), over-generation of cytokines and activated cells of innate immunity causes non-specific damage to tissues with local symptoms.

More importantly, the virus is not contained within the mucosal compartment, and escapes into the gas exchange part of the lungs. This brings into play the systemic immune system with its vigorous, uncontrolled activation of the foot-soldiers of innate immunity (the components of which differ from those recruited as “innate immunity” within the airways).

A key driver of systemic innate immunity are IgG antibodies. If IgG is present through vaccination or previous Corona viral infection (including COVID-19), the IgG antibody, through its activation and direction of innate immune mechanisms, rapidly disposes of the virus before any damaging hypersensitivity can occur. However, if no IgG antibody exists when a rapidly dividing virus enters the systemic compartment of the lungs, the consequences are very different.

Classical immunology teaches that an antibody-antigen immune complex with excess antigen promotes inflammation: in the context of COVID, inflammation manifests as pneumonia and serious disease.

Understanding these separate immune systems, each having its impact on different phases of viral infection, makes sense of the fact that vaccines have little impact on infection or infectivity (as they have little impact on mucosal immunity), but limit the severity of disease by preventing antigen-in-excess complexes forming when virus enters the gas-exchange section of the lungs.

There are major differences between the body’s primary immune response as seen in, say, measles immunisation and the antibody response from lymphoid tissue associated with mucous membranes.  The mix of lymphocytes in the peripheral lymph nodes is different.

Vaccines stimulate a vigorous IgG antibody response for either measles or CCOVID. But with the COVID vaccine suppressor cells are also stimulated that curtail the antibody response. So, with Covid, vaccination is followed by an immune response that is the balance of these two opposing reactions. Repeated vaccinations or infections could shorten the duration of antibody response to the infection as “suppression” dominates.

 

What is the actual experience with booster vaccinations, and what is the science behind this development of tolerance? Protection against severe disease and death and reducing admission to hospital have been the principal goals of COVID management. Recognition that a shift in disease severity was not the same as a reduction in infection was less well understood.

After about six months, infections in vaccinated subjects were reported more commonly and protection against more severe disease began falling. This was contrary to classic vaccinology, where protection lasted years due to the capacity of systemically primed (vaccinated) subjects to respond rapidly and vigorously to infection. This is known as the anamnestic response. In fact, IgG antibody levels following second COVID vaccine shots were blunted. In those developing COVID following vaccination, the expected antibody increase did not occur.

Over time it became clear that specific protection was not just lost in those with repeated vaccinations but became negative. This meant vaccinated subjects were more prone to infection than were unvaccinated subjects.

The best data came from Scotland and in the weekly UK government reports. For example, in the UKHSA report for week 9 (2022), COVID infections in immunised subjects were three times as common per 100,000 subjects, compared to unimmunised. Comparison of deaths in triple-vaccinated with unvaccinated subjects over the first eight weeks of 2022, shows protection by booster shots against severe disease and deaths lasted less than two months.

While this is a controversial area, consistent international data must be explained. My view is that these observations were predictable given that COVID is a mucosal disease.

Systemic vaccines specifically activate T- and B-cells seeded from mucosal lymphoid tissue, thus establishing a mix of positive (disease preventing) and negative (disease promoting) immune activities. Many factors influence this mix, and each activity has its dynamic and time course. Progressive reduction in duration of protection, followed by a trend towards infection promotion as found in a number of countries, is  consistent with this explanation.

The idea that mucosal infection produces both local and systemic tolerance or non-responsiveness began when questions were asked about why the body failed to develop an inflammatory response to leaked food antigen as 2 per cent of ingested protein is absorbed into the blood stream. Marion Sulzberger (1929), an eminent twentieth century dermatologist, then Merrill Chase (1947) described the phenomenon of abolition of dermal contact hypersensitivity to sensitising agents such as picryl chloride produced by prior oral feeding of the agent. Years of study led to recognition that the respiratory tract as well as the gut processed antigen via those carpets of dendritic cells, migrating to local lymphoid tissue to drive formation of T reg cells. These cells migrated to both mucosal and systemic sites to suppress immunity to the eliciting antigens.

Early studies in mucosal immunology showed that infection of the airways stimulated waves of consecutive positive and negative immune responses, and that mucosal T cells, obtained from resected human lung, powerfully inhibited specific systemic immunity.

Almost reversed are the data from desensitisation using injected allergens in those allergic to inhaled or ingested antigens. Two years of pre-season allergy shots induced a state of specific non-responsiveness to antigen exposure which lasted five years.

Taken together, studies on mucosal tolerance fit the observed data of COVID vaccines’ failure to achieve what was so lavishly promised in the pandemic’s early days, when public health officials and others promised what the mass media relayed to the public as the silver bullet that would tame and defeat the virus. This failure became more pronounced with repeated vaccinations involving poorly spaced boosters. The data from desensitisation of allergic subjects suggests that established T reg dominance following repeated COVID boosters may render the recipient prone to corona infections, including COVID, which has now been observed. In the longer term, and as antigen-induced tolerance can last years following desensitisation in allergic subjects, repeated poorly spaced boosters, threatens the value of seasonal corona virus vaccination post-pandemic.

 

♦ Can the immune response following vaccination cause adverse events?

Anaphylaxis, immune complex-mediated vasculitis, and exacerbations of existing autoimmune disease have all been documented. A link has been observed between the spike protein encoded by mRNA vaccines and life-threatening serious adverse events. mRNA vaccines cause spike protein to be produced in an unregulated way throughout the body, as detected in blood for two weeks following vaccination.  Thus, antigen is available for immune complex formation causing inflammatory lesions in blood vessels while spike protein on cell surfaces creates a target for potential autoimmune disease.  Additionally, spike protein is toxic to endothelium, cardiac and nerve tissue. Given the neurological adverse events reported following genetic vaccines, and the recent MRI evidence of reduced brain volume following Covid infection, similar studies are needed to exclude brain damage following the administering of mRNA vaccines.

German pathologists have described unusual lymphoid accumulations, microvasculitis and spike protein in damaged blood vessels after mRNA vaccination. Post-mortem studies in deaths post-vaccination must be standardised and extended to clarify the implications of these early studies.

 

CONCLUSION: The primary objective of this essay is to discuss the immunology of COVID-19 and its response to vaccination. If we accept COVID is a mucosal compartment infection, we can see why repeated unspaced vaccination can backfire. Many years of repeated infection by corona viruses that we encounter along the way establishes a state of regulated immunity with respect to the pandemic variant, COVID-19. Natural immunity and, to a greater extent, vaccine-induced immunity are limited. There is always the risk of dominant immune suppression, a risk amplified by repeated antigen stimulation.

Current data from many countries point to promotion of infection in subjects exposed to compressed booster programmes. Experience with allergy desensitisation points to the risk of long-term immune tolerance serving to compromise anticipated seasonal vaccination programmes for COVID.

Vaccines do, and will, play an important role in COVID management for the foreseeable future. Lessons from influenza vaccination, honed over decades, inform us that antigen vaccines using appropriately spaced periods will play an important public-health role into the future. Realistic outcomes for COVID-19 vaccines will be imprinted by experience with influenza vaccination.

Genetic vaccines have a long way to go to reassure their many critics they are safe, and that they offer any advantage over classical antigen vaccines. Replacing spike protein, or eliminating pathogenic sequences within it, is a challenge for those designing next-generation vaccines.

A strategic approach that combines exploration of optimal vaccine spacing with easily available safe, cheap, and effective drugs to manage intercurrent infections, makes scientific and clinical sense.

Acknowledgement: I thank Professor Stephen Leeder for his support, and superb editorial skills, to convert a science statement into an understandable communication.

Professor Robert Clancy AM MB BS BSc(Med) PhD DSc FRACP FRCP(A)  FRS(N) is a practising clinical immunologist with interests in autoimmune disease, immunisation and mucosal inflammatory disease. He was Foundation Professor of Pathology at the University of Newcastle, where he established the Newcastle Mucosal Immunology Group, identifying mechanisms of airways protection and the pathogenesis of mucosal disease, and discovered new methods of disease control

 

19 comments
  • Xebec

    Great sought after insights, thanks again Robert.

    Your last para. “A strategic approach that combines exploration of optimal vaccine spacing with easily available safe, cheap, and effective drugs to manage intercurrent infections, makes scientific and clinical sense” may not have been able to mention by name the safe, cheap, and effective drugs.

    They are of course, IVM, HCQ, VitD, Zinc, etc, etc. for which you often have advocated.

    And after “spacing” perhaps current vaccines should only be for the elderly and vulnerable,
    as you clearly point out the hazards of repeat vaccination with these genetic vaccines on the immune system. A price too high for those less frail with healthy immune systems.

    As you say, speed on the next generation of vaccines for which you hope, along with advice from health bureaucrats as to how we can optimise our individual Immune health.

  • exuberan

    Would Dr Clancy please clarify which drugs he is referring to in the last paragraph. If indeed he is referring to IVM and HCD would the Doctor please further advise if these drugs are in his own personal pill cabinet. Also, how many vaccinations has the Doctor had please? Always easier in hindsight and the point on developing immunity is good for those who are fit and healthy with no underlying health issues. The Health Departments in Australia had to cater for ALL Australians and in a big hurry. They might now also be reflecting on past actions and might even agree with Dr Clancy.

    • Robert Clancy

      “My families experience with Covid and its vaccines is a microcosm of the above. Yes, all my family including myself, are “double vaxed”. My wife and I will have an “antigen-based” booster (NovaVax), 12 months after our second vaccine dose, as the best data re “spacing” is a 12 month interval (experience with influenza vaccines).

      Two close family members had life-threatening adverse events following mRNA vaccines, and were admitted to a major Sydney teaching hospital. Neither event was reported to the TGA as an AE (it seems the narrative is more important than the reality).

      Four close family members have been infected with Covid-19. Three are aged over 45 years and have been treated successfully with ivermectin-based combination therapy (two had additional risk factors).

      My wife and I both take prophylactic hydroxychloroquine.”

  • rod.stuart

    In a converstion with Dr. John Campbell, Professor Clancy explained that within the mucosal compertment, mucus is continually transported in the mouth (at the rate of about a cupful per day) after which it is swallowed. I can relate to this since I have Bonchiectasis and so the auto transport mechanism has failed and it is a conscious effort to produce the result.
    Consequently a patch in the small intestine has the capacity to analyse the viral material from the mucosal compartment and to create the IgA and IgG which it then “sends” special delivery through the lymphatic system to various parts of the body where it is required. I found that fascinating.
    Professor Clancy please correct me if I misunderstood your explanation to Dr. Campbell.

  • ianl

    Thank yoiu for the clarity, Dr Clancy.

    The MSM will ignore this because their scientific understanding is almost non-existent, so clinging to current bureaucratic “consensus” seems safer to them.

  • Stephen Due

    Robert, many thanks for this clear and concise summary of a complex scenario!
    Some comments:
    (1) Under your heading “Can the immune response following vaccination cause adverse events?” you include the vital information that it is not only the immune response but also the vaccine itself that is toxic, damaging the vascular and neurological systems. We know, in addition, that the vaccine material accumulates in the ovaries and appears also to be causing damage there, the effects of which include dysregulated menstruation and infertility.
    (2) Because of the deficiencies of these experimental gene therapies, logic dictates that persons who are not at risk from the disease should not be vaccinated with them. This applies particularly to children.
    (3) Whether the vaccines really do reduce the severity of infection has not in my view been demonstrated. There are many confounding factors, and no clear trial data. In the context of the ready availability of cheap and effective drug treatments – sadly banned in Australia and elsewhere to promote the vaccines – it is doubtful whether vaccination confers any benefit at all, particularly in the case of persons who have already been infected and have recovered. In view of the vast scope of the known adverse effects, the likelihood that there is any overall benefit from the vaccines seems quite small.

  • Stephen Due

    Having digested the contents of this informative article, readers might like to visit the Australian Government Department of Health’s website by way of comparison. Truth takes a back seat when government officials get to work to manipulate and deceive the public. Of course, this is only for our own good. The authorities, who consider themselves to be members of an elite intelligentsia, know that the public need to be addressed as infants of little mental capacity.
    The website, therefore, is festooned with dozens of simpering, simplistic statements expressly designed to reassure the public that the government is keeping them safe, while ignoring the minor matter of (in most instances) a complete absence of scientific evidence.
    One statement that is especially noteworthy is the following:
    “You may not be fully protected against COVID-19 until 7 to 14 days after your second dose or booster”.
    In fact you will not be “fully protected against COVID-19” at all, ever, by these vaccines, no matter how many “doses or boosters” you have.
    What the authorities will undoubtedly say, if you ask them about this duplicitous statement, is that you will not have acquired the maximum protection afforded by the vaccine until you have a second dose or booster. To the untrained eye, that is not the same as being “fully protected”. A sleight of hand is taking place here, a little magic trick that turns an ineffective product into something truly wonderful.
    These vaccines use clever technology, but they are also expensive, toxic products that behave unpredictably in the human body. They have killed and maimed a lot of people, although according to the authorities this is fine because statistically the killings and maimings are ‘rare’.
    The authorities do not actually know what is in these vaccines (trade secrets). They have no scientific information about their long-term effects. In reality, this is a vast, irresponsible, effectively unregulated, uncontrolled scientific experiment. It would be nice to think justice might be done eventually, but justice, like reason and evidence, seems to be in short supply in these days.
    The one bright spot is that there are people like Robert Clancy, along with Robert Malone and others, who are working hard to honestly inform the public and restore the reputation of medical science.

  • jackgym

    Sing this song to your doctor, replacing alouette with Ivermectin:
    Alouette, gentille alouette,
    Alouette, je te plumerai.

  • Stephen Due

    See also the recent 52-page letter from the (Australian) Covid Medical Network to the Australian Therapeutics Advisory Group on Immunisation (ATAGI), the CMO, the Therapeutic Goods Administration (TGA) and the Minister of Heath:
    https://www.covidmedicalnetwork.com/open-letters/Letter-to-ATAGI-TGA-FedHealth-8MarchFINALsignatures2.pdf

  • vickisanderson

    Professor Clancy has chosen an extremely diplomatic argument to persuade the advocates of the genetic vaccines to think again.

    To my simple mind, he is basically advising the vaccinologists to go back to traditional antigen vaccines as are used to combat influenza, and to forget these Trojan horse vaccines which release enemies, rather than friendly combatants, into our bodies.

    No mention this time of Ivermectin – even as a research document has just been released which shows its efficacy in countering Japanese Encephalitis, which is inciting the media into new hysteria in the media.

  • Peter C Arnold

    Why do so many scientific commentators ignore the genetics of people encountering Covid-19? A partial explanation (or perhaps the whole, for some people) would be their individual genetic susceptibility to the virus’s attack on their cells. With the mildness of the illness for most affected people, and the low serious illness and death rates cf the 1917-19 influenza, why are individual genetics being ignored?
    Peter Arnold, former GP.

  • mpaine

    Professor Clancy’s views are of vital importance. He is mostly retired so I assume somewhat protected from the cancelling of those who step outside of the ‘narrative’. So do I understand this post correctly?
    The mrna vaccines are experimental genetic therapies.
    They do seem to alleviate the severity of covid.but for a limited time.
    They do not prevent the contracting or the spreading of covid.
    The booster should be treated with caution. It has even more limited duration.We are seeing negative efficacy with these vaccines – you are more likely to get covid if you are vaccinated and could be why we are seeing so many folk getting multiple cases of covid – particularly just after vaccination. Haven’t we been told that the immune system is compromised for a week or so after vaccination?
    Great – get the toxic spike protein into your cells so your body makes it for goodness knows how long. It travels all over the body triggering poorly controlled and limited immune responses. It lessens severity for a brief window of time but you will catch covid more often and should not get vaccinations too close together. Tell me again why employers are mandating vaccinations and we are delivering our precious children to the vaccinologists. Professor Clancy seems to be recommending we develop traditional vaccines and use treatments stead of the mrna vaccines.
    Can we just say so simply, clearly and loudly and stop these poor people losing their jobs.because they are reluctant to be vaccinated. It seems a reasonable position to me..

  • andrew2

    Hi Professor Clancy, Thank you for posting this article. I have a question regarding the following quote:

    “…while spike protein on cell surfaces creates a target for potential autoimmune disease. Additionally, spike protein is toxic to endothelium, cardiac and nerve tissue.”

    If the spike protein is responsible for such issues, do “antigen-based” vaccines such as Novavax which contain a manufactured dose of the spike protein pose a similar risk? Or is it just the fact that mRNA vaccines produce an unregulated amount of spike protein that makes them likely to produce more spike protein or have spike protein in the blood stream for a longer period of time that makes them particularly dangerous in these areas? Is Novavax safer simply because the amount of spike protein is pre-determined and the damage it can cause is limited by this?

    I’m in the process of organising to be vaccinated with Novavax. Despite the requirement to have two doses to be fully vaccinated I’m tempted to only have one dose as my goal is not to be “fully vaccinated” but simply to prevent severe disease. Can you see any flaw with this approach? Thanks in advance.

  • ArthurB

    Andrew: I am also interested in this question, since I refused to be Jabbed with one of the mRNA vaccines, but because of pressure from family and friends I had no option but to be vaccinated, and chose Novavax, I had the first shot last week, so far no problems. In WA you have to be double vaxxed, otherwise you are forbidden to enter hospitality venues, etc.

    I have absolutely no doubt that the mRNA vaccines are potentially lethal, but I guess it will take time before we discover whether the conventional vaccines have any effects that will be manifested only after a long time.

  • lbloveday

    “I have absolutely no doubt that the mRNA vaccines are potentially lethal”
    .
    The Tasmanian Coroner concluded:
    I am satisfied on the evidence to the requisite legal degree that Mr Reed dies of an adverse reaction to the AstraZeneca vaccine for COVID19.

    https://www.magistratescourt.tas.gov.au/__data/assets/pdf_file/0008/652427/Reed,-Ian-William-McDonald.pdf

  • lbloveday

    died not dies

  • john2

    I was talking to a couple of young blokes the other day and the subject of asbestos came up (in the context of the excellent insulating properties of asbestos building materials). They were both acutely aware of the dangers of asbestos, but seemed not to know how great it was as an insulator, fire-retardant and heat-resistant material. I explained that these properties led to its popular, widespread use in many applications. Unfortunately, the conversation ended there, and I missed the opportunity to observe that yesterday’s “safe and effective” wunder-produkt can backflip to become today’s demonic scourge – especially when rigorous and prudential regulatory approval processes are so easily short-circuited.

  • rosross

    It is hard to see how the Covid Jabs can offer any benefits given the huge increase in cases and hospitalisations where Jab campaigns have made an impact.

    From the data coming in it looks like being Jabbed, and the more Jabs the worse it gets, means a greater chance of serious illness for people.

    I understand the pressure on professionals to maintain the Jab narrative but surely there must be a growing understanding that not only do the Jabs not confer any benefits they make it all much worse.

  • Lewis P Buckingham

    ‘for potential autoimmune disease’
    Speaking to a sufferer of Hashimoto’s disease she commented that her endocrinologist has noticed a rise in cases after vaccination.
    This is a devastating disease.
    Any vaccine needs be screened for such a side effect.

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