[The] BNT162b2 vaccine also modulated the production of inflammatory cytokines by innate immune cells upon stimulation with both specific (SARS-CoV-2) and non-specific (viral, fungal and bacterial) stimuli. The response of innate immune cells to TLR4 and TLR7/8 ligands was lower after BNT162b2 vaccination. [Emphasis added].
[W]e observed a significant reduction in the production if IFN-α secreted after stimulation with poly I:C and R848 after the administration of the second dose of the vaccine (Figure 1H, 1I). This may hamper the initial innate immune response against the virus, as defects in TLR7 have been shown to result in and increased susceptibility to COVID-19 in young males (Van Der Made et al., 2020). These results collectively demonstrate that the effects of the BNT162b2 vaccine go beyond the adaptive immune system and can also modulate innate immune responses. [Emphasis added].
Three concerns are raised by the above.
- The ability of the immune system to fight viruses has been diminished; specifically, the ability to fight SARS-CoV-2 may be affected;
- Vaccine-induced innate immune tolerance may affect other vaccines; and finally
- What other parts of the immune system may be affected.
On social media and online magazines we are now seeing reports of patients with worsening cancer following SARS-CoV-2 vaccination; headlines like the following:
In the articles above, any causal effect by the vaccine is quickly dismissed, and one patient praises the vaccine for saving her life:
Moseley noted that she had a routine mammogram scheduled in July. But if she hadn’t been vaccinated in April and discovered the swollen lymph node, her cancer could have grown before it was detected. “The COVID-19 shot, I’m gonna say-as much as COVID sucked-it saved me,” she told the Des Moines Register.
A benign, swollen lymph node caused by the vaccination alerted her to check for signs of cancer, which she found. A doctor explains this phenomenon in the Lifestyle section of News.com.au:
Dr. Laura Esserman, director of University of California San Francisco’s Breast Care Center, said women were confusing swollen lymph nodes after the vaccine for signs of cancer.
For Moseley, it was fortuitous: She had cancer.
There is a genuine concern over an increase in cancer, not from vaccination, rather as a result of lockdown and limited medical access. However, others are not convinced by the prevailing narrative and suspect that SARS-CoV-2 vaccination is contributing:
Dr Ryan Cole, a Pathologist, in a recent presentation, stated that he is observing a 20 x uptick in endometrial cancer, and increases in other cancers post SARS-CoV-2 vaccination.
And even more concerning: a senior consultant with decades of diagnosis and treatment at a dedicated cancer hospital described to a journalist off the record that all his vaccinated cancer patients were coming out of remission; and that cancer was jumping between organs, spreading at a speed that he has never seen before (pers. Comm.).
At this stage, these reports are anecdotal but if they reflect a hitherto hidden change in the nature of how cancer is affecting patients post vaccine, then what would be the mechanism? And to what degree might it be obscured, even if just initially, by the expected increase in morbidity and mortality as a result of lockdown and limited medical access?
This would be an interesting intellectual exercise were it not for the original question that did not seem to be adequately asked and answered: but what would be the consequences of switching off that important early warning system?
The answer to that may just be echoing the embryonic observations of doctors such as Ryan Cole.
A clinical clue, albeit reported in low numbers at the moment, possibly supporting the work of Dominguez-Andres et al, and may be immunologically linked to Dr Cole’s observations, appeared as reactivation of Varicella Zoster Virus after vaccination for Sars-Cov-2:
Seven immunocompetent patients aged > 50 years old presented with herpes zoster (HZ) infection in a median of 9 days (range 7–20) after vaccination against SARS-CoV-2. The occurrence of HZ within the time window 1–21 days after vaccination defined for increased risk and the reported T cell-mediated immunity involvement suggest that COVID-19 vaccination is a probable cause of HZ. [Emphasis added].
The data were consistent with the vaccine causing changes to the immune system that made the recipient more vulnerable to developing a herpes zoster (HZ) infection.
Furer et al in Herpes zoster following BNT162b2 mRNA COVID-19 vaccination in patients with autoimmune inflammatory rheumatic diseases: a case series published in the Journal of Rheumatology also reported:
Potential mechanisms that might explain the pathogenetic link between mRNA-COVID19 vaccination and HZ reactivation are related to stimulation of innate immunity through toll-like receptors (TLRs) 3,7 by mRNA-based vaccines. TLR signalling has been implicated during reactivation of herpesviruses, a process essential for these viruses to maintain themselves in the host. Defects in TLR expression in patients suffering from diseases caused directly by herpesvirus infection highlight the importance of these signalling pathways during infection and eventual disease progression. The vaccine stimulates induction of type I INFs and potent inflammatory cytokines, which instigate T and B immune responses but may negatively affect antigen expression potentially contributing to HZ reactivation.
Both aforementioned studies implicating parts of the immune system post SARS-CoV-2 vaccination in HZ infection. One might say: well, those studies have a significant number of older patients; the first study had a mean age of 77yrs, and they have other health problems, and there may be other explanations. For example Methotrexate, a widely prescribed drug for immune mediated inflammatory disease that may be associated with older age, has been questioned in the past for its effect on HZ infection with some studies supporting a causal role, and others not. And more recently, Methotrexate significantly hampered the immune process post Pfizer vaccine for Sars-Cov-2. But the patients in the reactivation study did not appear to be on that drug.
We must also note that HZ infection has also been observed in Covid-19 cases, and not just the elderly:
While there have been cases of varicella-zoster virus reactivation due to COVID-19 or COVID-19 vaccine inoculation in older individuals with pre-existing conditions, this case report describes the first case of varicella-zoster virus reactivation on a healthy, young male in the absence of pre-existing conditions. The mechanisms underlying varicella-zoster virus reactivation in patients with COVID-19 are unknown and should be further characterized. [Emphasis added].
Therefore, both Covid-19 infection and SARS-CoV-2 vaccination have been associated with HZ infection. How many others have had a similar reaction but have gone unidentified?
Indeed, the mechanism needs to be characterised, and does it involve dysfunctional toll-like receptors? The above studies think so and blame the stimulation of specific toll-like receptors.
Toll-like receptors do play an important role in herpes infection; and TLR2, 3 & 9 specifically in Varicella Zoster infection; and any potential change in their function may therefore impact the body’s ability to control HZ infection.
Although, research has not demonstrated post vaccine effects on TLR2 and 9 (please see below for TLR3), we are reminded of the statement made by Dominguez-Andres et al regarding the other toll-like receptors:
The response of innate immune cells to TLR4 and TLR7/8 ligands was lower after BNT162b2 vaccination.
They did also reported changes in TLR3, more specifically involved with Varicella Zoster infection but did not meet statistical significance:
TNF-α production (Figure 1B-1G) following stimulation with the TLR7/8 agonist R848 of peripheral blood mononuclear cells from volunteers was significantly decreased after the second vaccination (Figure 1C). The same trend was observed after stimulation with the TLR3 agonist poly I:C (Figure 1D), although the difference did not reach statistical significance. [Emphasis added].
We can see from the above research that scientists are concerned that parts of the immune system are being negatively affected both by Covid-19 infection and SARS-CoV-2 vaccination that may be leading to reactivation of Varicella infection. Stimulation of toll-like receptors has been suggested, but the implicit design of the mRNA SARS-CoV-2 vaccines is such that they will stimulate certain toll-like receptors less; TLR 7 & 8 are RNA sensors and would be affected by Uridine changes to vaccine mRNA. TL4 would not.
Regardless, researchers have demonstrated that The response of innate immune cells to TLR4 and TLR7/8 ligands was lower after BNT162b2 vaccination. And that’s not good for the innate immune response.
The immune system is highly regulated with interconnected paths that immunologists are still discovering, and by changing one part you affect another. If SARS-CoV-2 vaccination is changing something in our immune system, be it via changes in vaccine mRNA code and negatively affecting toll-like receptors or by other means, what else does it change in our immunity?
We have already seen a clue to that in the research we have covered but to expound let us consider the following:
Lynn et al describe the importance of toll-like receptors in Impact of Polymer-TLR-7/8 Agonist (Adjuvant) Morphology on the Potency and Mechanism of CD8 T Cell Induction:
Small molecule Toll-like receptor-7 and -8 agonists (TLR-7/8a) can be used as vaccine adjuvants to induce CD8 T cell immunity. [Emphasis added]
InvivoGen summarising Craft et al (2005) & Reece et al (2005) support that finding:
The ability of TLR7-8 agonists to activate DCs and thus elicit Th1 and CD8+ T cells responses can be exploited to enhance the efficacy of vaccination. [Emphasis added]
From those authors, we see an important connection between toll-like receptors, dendritic cells (DC) and T cells, specifically CD8 T cells.
Toll-like receptors activate dendritic cells, eliciting a response from CD8 T cells. CD8 T cells are established as a vital part of the immune system’s defence against infection but also cancer.
Fu and Jiang in Dendritic Cells and CD8 T Cell Immunity in Tumor Microenvironment explore the complex interplay further and reveal the importance of dendritic cells in the role CD8 T cells play in fighting cancer:
While direct presentation of tumor antigens onto their MHCI by tumor cells play an important role in effector function of CD8 T cells, cross-presentation by professional antigen presenting cells in particular DCs are required for prime naive CD8 T cells and sustaining the cytotoxic immune responses. [Emphasis added].
If, as the authors state, that toll-like receptors are required to activate dendritic cells, and dendritic cells sustain T cell cytotoxic killing against cancerous tumours, then what happens if those toll-like receptors are not working so well?
An uptick in cancer? And infection?
The toll-like receptors 7 & 8 are described in the literature as important in eliciting the vital CD8 T cell response. With that in mind, let us remind ourselves what Drs. Weissman and Kariko wrote in 2005 in Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA:
We show that RNA signals through human TLR3, TLR7, and TLR8, but incorporation of modified nucleosides m5C, m6A, m5U, s2U, or pseudouridine ablates activity.
That very technology is being used in SARS-CoV-2 vaccines: It switches off TLR 7 & 8 signalling, that the immune system needs to fight infection and cancer.
Changes to key parts of the mRNA code in SARS-CoV-2 vaccines may be causal in changing the innate immune response via toll-like receptors. Toll-like receptors are important components in defence against infection and downstream effects may also include inhibition of CD8 T cell response. CD8 is a vital part of the immune system’s ability to eradicate infection and cancer. Those changes may be reflected in recent reactivated Varicella Zoster infections although specific mechanisms are unclear at the moment. Anecdotal reports of significant uptick in cancer presenting to medical consultants may be consistent with aberrant toll-like receptor and dendritic cell changes leading to an inhibition of the anti-cancer CD8 effector response. Further data are required but the prospect of an altered CD8 response to infection and cancer is very concerning and should prompt urgent investigation.
One might be forgiven for asking: surely someone must have cautioned against doing that? And isn’t that why new drug/vaccine products are supposed to be thoroughly tested before they are given to large populations?