Introduction
​
The aim of this article is to demonstrate the need for further investigation into the link between
Covid-19 mRNA injections and the recent rise in cancer cases Worldwide.
It has been observed by many in the medical research community that repeated Covid-19 mRNA
injections produce large quantities of an antibody called igG4 (immunoglobulin G4) which
subsequently turns off the human body’s ability to identify and destroy cancer cells and other severe
disease.
The development of this large quantity of igG4 is usually around the third Covid-19 mRNA
injection according to the literature and occurs via a mechanism called class switching where other
antibodies igG1 and igG3 convert to igG4 and igG2 after a period following inoculation.
There are 4 subclasses of igG antibodies with 1 and 3 being the ones with the highest potential to
activate a positive immune response and are generated initially after receiving a Covid-19 mRNA
injection. Preliminary test results from the Covid-19 mRNA injections will appear promising for
fighting infection but because of the class switching this quickly diminishes and breakthrough
infections will become prevalent and little to no protection will be given. Also immune responses
will be deactivated leaving individuals more susceptible to disease than prior to the mRNA
treatment due to the inhibitor action of igG4 on Natural Killer and igG1 and igG3 antibodies.
There is only a relatively small amount of research on this particular subject but what has been
conducted clearly proves that further investigations are urgently needed, and a reevaluation of the
requirement that these injections be offered to people as a beneficial therapeutic by our healthcare
services.
Below is a collection of published medical journal excerpts which establish a decent foundation for
this hypothesis and a clear urgency to push this issue forward for a comprehensive inquest.
Post-vaccination IgG4 and IgG2 class switch associates with increased risk of
SARS-CoV-2 infections
https://www.sciencedirect.com/science/article/pii/S0163445325000672
Repeated COVID-19 mRNA vaccinations increase SARS-CoV-2 IgG4 antibodies, indicating
extensive IgG class switching following the first booster dose. This shift in IgG subclasses raises
concerns due to the limited ability of IgG4 to mediate Fc-dependent effector functions.
Here, we show that higher levels of IgG4 and IgG2, as well as higher proportions of non-cytophilic
to cytophilic antibodies, following booster vaccination, are associated with a heightened risk of
SARS-CoV-2 breakthrough infection. Conversely, IgG1 levels, C1q- and Fcγ receptor-binding
antibodies and neutralization capacity are associated with protection.
Our study aligns with previous research showing a sharp increase in IgG4 and IgG2 levels
following three doses of mRNA vaccination against SARS-CoV-2,1, 2 but goes beyond the state-of-
the-art by associating this switch with decreased neutralization, Fc-effector functionality, and
protective immunity.
Nevertheless, while our findings indicate that higher IgG4 and IgG2 levels are associated with an
increased risk of SARS-CoV-2 breakthrough infection, these less immune-activating subclasses may
also help prevent severe COVID-19 by mitigating inflammation-driven pathology.20 Previous
studies have also reported negative correlations between Fc-effector functions and IgG4 induction.
For instance, ADCP phagocytosis scores and ADCD were reduced after the third mRNA vaccine
dose compared to the second dose, with these reductions correlating with increased anti-S IgG4
levels.1 Similarly, a higher anti-S IgG4/IgG1 ratio after SARS-CoV-2 mRNA vaccination was
associated with diminished NK (Natural Killer) cell activation and ADCD.6 Beyond its reduced
ability to engage effector functions, IgG4 is functionally monovalent due to its capacity for Fab-
arm exchange,21 which may limit its ability to form immune complexes and effectively neutralize
pathogens.
(From Google: Natural killer (NK) cells, a type of white blood cell, are crucial for the body's innate
immune system, playing a vital role in detecting and eliminating virus-infected and cancerous cells,
as well as regulating other immune responses.)
Both IgG2 and IgG4 B-cells typically accumulate high levels of somatic hypermutations, indicative
of extensive affinity maturation. This suggests that antibodies of these subclasses may exhibit high
binding affinities for their target antigens, which is generally important for neutralization.
However, despite this potential for high affinity, we observed a negative association between
IgG2 and IgG4 levels and neutralizing antibody responses.
The underlying mechanisms driving class-switch recombination towards IgG4, especially after
repeated COVID-19 mRNA vaccination, are still unclear. It has been hypothesized that persistent
germinal centre responses induced by mRNA vaccination22—possibly driven by the prolonged
presence of vaccine mRNA or antigen in lymph nodes23—may facilitate class switching toward
distal subclasses such as IgG4.2
IgG4 Antibodies Induced by Repeated Vaccination May Generate Immune
Tolerance to the SARS-CoV-2 Spike Protein
https://pmc.ncbi.nlm.nih.gov/articles/PMC10222767/
Additionally, recent investigations have found abnormally high levels of IgG4 in people who were
administered two or more injections of the mRNA vaccines. HIV, Malaria, and Pertussis vaccines
have also been reported to induce higher-than-normal IgG4 synthesis. Overall, there are three
critical factors determining the class switch to IgG4 antibodies: excessive antigen concentration,
repeated vaccination, and the type of vaccine used. It has been suggested that an increase in IgG4
levels could have a protecting role by preventing immune over-activation, similar to that occurring
during successful allergen-specific immunotherapy by inhibiting IgE-induced effects. However,
emerging evidence suggests that the reported increase in IgG4 levels detected after repeated
vaccination with the mRNA vaccines may not be a protective mechanism; rather, it constitutes an
immune tolerance mechanism to the spike protein that could promote unopposed SARS-CoV2
infection and replication by suppressing natural antiviral responses. Increased IgG4 synthesis
due to repeated mRNA vaccination with high antigen concentrations may also cause autoimmune
diseases, and promote cancer growth and autoimmune myocarditis in susceptible individuals.
Repeated COVID-19 mRNA vaccination results in IgG4 class switching and
decreased NK cell activation by S1-specific antibodies in older adults
https://immunityageing.biomedcentral.com/articles/10.1186/s12979-024-00466-9
Immune checkpoint inhibitors, often known as cancer immunotherapy agents, prevent checkpoint
proteins from attaching with their associated polypeptides, allowing cytotoxic CD8+ T lymphocytes
(CTLs) to attack cancer cells. Immune checkpoint-blocking (ICB) agents include anti-CTLA-4
(cytotoxic T-lymphocyte antigen 4) and anti-PD-1 (programmed cell death protein 1) monoclonal
antibodies [87,88]. ICB has demonstrated therapeutic effectiveness in a wide range of cancer types,
including advanced-stage cancer patients [89,90,91]. Regrettably, only 15–30% of cancer patients
who have received treatment benefit from ICB’s therapeutic efficacy [92]. Most crucially, new
reports show that certain cancer patients receiving anti-PD-1 monoclonal antibody treatment have
rapid disease progression (also known as hyper progressive disease (HPD) instead of cancer
remission [93,94,95]. Notably, the PD-1 antibody belongs to the IgG4 family. Furthermore,
cancers, such as malignant melanoma [48], extrahepatic cholangiocarcinoma [96], and
pancreatic cancer [97], have been linked to plasma B-cell infiltrates that are IgG4-positive.
IgG4′s contribution to cancer is poorly understood, but a groundbreaking study has added
important new knowledge. Karagiannis et al. [48] studied malignant melanoma and found that IL-4
and IL-10 expression was elevated and that tumour-specific IgG4 was generated locally in the
tumor tissues. It is common to think of IL-10 as an anti-inflammatory cytokine; however, this is only
true in low quantities, as at larger concentrations, it shows pro-inflammatory effects [98,99,100].
Karagiannis et al. [48] also found that, in contrast to cancer-specific IgG1, cancer-specific IgG4
failed to activate two immunological processes that employ antibodies to identify and destroy
cancer cells. Moreover, the IgG1 antibody was able to suppress cancer progression in an in vivo
model, while IgG4 failed to do so. IgG4 antibodies cannot directly attack tumour cells and can
interfere with the process of tumour cell death mediated by IgG1 antibodies. The inhibition of
IgG1 binding and activation by Fc RI is the mechanism behind this obstructing activity. Such
findings point to a previously un-researched feature of tumour-induced immune escape: IgG4
synthesis induced by tumours limits effector immune cell activities against tumours [48]. Another
work [101] came to the same conclusion; that is, the IgG4 antibody is important and necessary
for cancer immune evasion. In a cohort of individuals with esophageal cancer, B cells producing
high IgG4 concentrations were markedly raised in malignant cells and also high in serum samples
from patients. More IgG4 seems to be linked to more aggressive cancer growth, and both were
strongly associated with higher cancer malignancy and poor prognosis. It was discovered that
IgG4 can contend with IgG1 (as shown in Figure 3) in binding to Fc receptors present in some
immune cells in vitro. This competition results in the inhibition of typical immune responses against
cancer cells, such as cell and complement cytotoxicity and cell phagocytosis, which are mediated
by IgG1 antibodies.
Waning immunity and IgG4 responses following bivalent mRNA boosting
https://www.science.org/doi/10.1126/sciadv.adj9945
Studies have shown that COVID-19 mRNA vaccines and adenoviral-vectored vaccines induce
preferentially IgG1 and IgG3, with limited IgG2 and IgG4 in both humans and nonhuman primates
(20–22). However, recent longitudinal follow-up studies after a second or third monovalent
mRNA vaccination showed evidence of some class switching toward IgG4 (23, 24). Further
evolution of IgG subclasses after a fourth mRNA vaccination remains unknown.
IgG subclass and functional responses following bivalent mRNA boosting
To explore in greater detail spike-specific antibody responses following bivalent mRNA boosting,
we assessed IgG subclass responses (IgG1, IgG2, IgG3, and IgG4) against WA1/2020, BA.1, BA.2,
BQ.1.1, and XBB.1.5 following bivalent mRNA boosting. Less than twofold increases in IgG1
responses were observed to WA1/2020, BA.1, BA.2, BQ.1.1, and XBB.1.5 at week 3 and returned to
preboost levels by month 3 (Fig. 4AOpens in image viewer). A similar trend was observed with
IgG3 responses. Slightly higher 4.9-, 2.7-, 1.9-, 1.7-, and 1.5-fold increases in IgG2 responses were
seen to WA1/2020, BA.1, BA.2, BQ.1.1, and XBB.1.5 at week 3 (Fig. 4AOpens in image viewer). In
contrast, markedly higher 11.2-, 11.0-, 9.1-, 8.5-, and 7.8-fold increases in IgG4 responses were
observed to WA1/2020, BA.1, BA.2, BQ.1.1, and XBB.1.5 at week 3, and these responses were
durable at month 3 (Fig. 4AOpens in image viewer). These results suggested that bivalent mRNA
boosting did not substantially increase proinflammatory IgG1 and IgG3 responses but rather
skewed responses primarily to isotype-switched IgG4 responses.
A class switch toward IgG4 happens usually when an individual is frequently exposed to an antigen
(19, 47), which was demonstrated in a study with beekeepers, where IgG1 antibodies specific to
phospholipase A2, a bee venom antigen, class-switched to IgG4 after 6 months of continuous bee
stings (48). Similarly, in the HIV vaccine trial RV144, where participants received canarypox
vector–based HIV Env vaccines and purified HIV Env gp120 protein vaccines, elevated IgG1 and
IgG3 antibodies correlated with enhanced effector functions, whereas in the clinical trial VAX003,
where participants received seven doses of HIV Env gp120 protein vaccines, elevated IgG2 and
IgG4 levels were observed with increasing boosts and correlated with inhibition of Fc effector
functions (49–51). We speculate that a class switch from IgG1 to IgG4 might occur after multiple
mRNA immunizations (23). This is also in line with an observation that class switch to IgG2 or
IgG4 occurs more readily from IgG1 B cells (52), potentially to balance excessive inflammation,
as IgG4 is known to have inhibitory effector functions
Cytokine Storms and Anaphylaxis Following COVID-19 mRNA-LNP
Vaccination: Mechanisms and Therapeutic Approaches
https://pmc.ncbi.nlm.nih.gov/articles/PMC11507195/
Recent reports have indicated that frequent mRNA vaccination may induce a gradual increase in
TRAb levels and promote a class switch to IgG4, which could contribute to long-term immune
responses and might be considered potential late-onset adverse reactions [12,13]. Additionally, it
has been suggested that the use of 100% N1-methyl-pseudouridine (m1Ψ) in mRNA vaccines may
pose a potential risk of promoting cancer development in the long term, as m1Ψ has been
associated with immune suppression and the facilitation of tumor growth and metastasis in certain
models [14].
mRNA vaccines against SARS-CoV-2 induce comparably low long-term IgG Fc
galactosylation and sialylation levels but increasing long-term IgG4 responses
compared to an adenovirus-based vaccine
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1020844/full
Instead, the mRNA, but not the adenovirus-based vaccines induced long-term IgG4 responses – the
IgG subclass with inhibitory effector functions.
Nevertheless, all three vaccines seem to induce high protection from severe disease conditions in
the next weeks after a second immunization (5, 18, 19), assuming a robust long-term systemic T and
B cell response – also against non-RBD parts of the virus and virus escape variants (15). However,
the influence of the different new vaccine formats with unclear co-stimulatory/”adjuvant” effects on
the long-term B cell and Ab Fc response remains unknown.
IgG Fc-mediated effector functions are influenced by the induced IgG subclass and the IgG Fc N-
glycosylation pattern. Human IgG1 and IgG3 subclasses have been described to convey the highest
potential to activate immune cells via classical activating Fcγ receptors (FcγRs) and the classical
complement pathway via C1q (20–24). These IgG subclasses can form hexamers, thereby
facilitating the interaction with the six-arm C1q molecule (21, 25–29). IgG2 hardly interacts with
classical FcyRs and C1q and its effector function-inducing capacity needs further investigation (20,
22, 23). In contrast, IgG4 shows higher affinity to the classical IgG inhibitory receptor FcyRIIB
than to classical activating FcyRs (20, 22, 23). Furthermore, IgG4 cannot activate C1q but
instead is able to disturb the hexamer formation of the C1q-activating IgG subclasses (21).
Furthermore, IgG4 can generate Fab arm-exchange, meaning that heavy chains with different
specificities can dimerize resulting in bispecific Abs, which reduces their ability to form immune-
complexes (30). Thus, IgG1 and IgG3 are the IgG subclasses with the highest potential to activate
the immune system, whereas IgG4 has less activating potential and can even inhibit the effector
functions of IgG1 and IgG3.
Exploring the possible link between the spike protein immunoglobulin G4
antibodies and cancer progression
https://www.explorationpub.com/Journals/ei/Article/1003140
However, after the second mRNA vaccine injection, an unexpected long-term side effect has been
observed worldwide: a switch in the isotype of IgG antibodies took place. Before the emergence of
these observations in the general mRNA vaccinated population, this phenomenon appeared to have
been documented in single individuals and described as a rare vaccine side effect; either producing
IgG4-related disease (RD) [9–13] or experiencing a relapse of IgG4-RD symptoms [14]. The
phenomenon of rising IgG4 antibodies post mRNA vaccination has now been documented in
studies involving human participants [8, 15–28] and at least one animal study [29]. It appears
that the rate of increase of IgG4 antibodies can surpass all other IgG antibodies developed
towards the spike protein, rising consistently from an average of 0.04% after the second
immunization to 19.27% after the third one [8]. This was echoed by another study, where the
median level of IgG4 antibodies directed against the spike protein was 21.2% of all IgG antibodies
[19]. In stark contrast, this phenomenon has not been reported in non-vaccinated individuals [16,
17, 23, 25, 27] )
Roles of immunoglobulin G4 (IgG4) antibodies in local immune escape. Under normal conditions,
the IgG1 antibody recognizes the cancer-associated antigen. IgG1 then binds through the fragment
crystallizable (Fc) to its receptor, located on the natural killer (NK) cells (shown) or macrophages
These are activated and NK cells release perforins and granzymes that destroy the cancer cell while
macrophages phagocytose the cancer cell. However, when present, IgG4 could bind to the Fc
region of the IgG1 antibody, thus inhibiting its union with its respective receptor located on the
NK or macrophage cell. As a consequence, these effector cells are not activated and therefore
cannot destroy the cancer cell.
Impairment of anti-tumour responses by immunoglobulin G4 (IgG4) antibodies engaging inhibitory
FcγRIIB receptors. In normal circumstances, macrophages can recognize and eliminate cancer
cells by phagocytosis. Tumours nevertheless continue to grow despite their presence. Some cancers
have evolved immune evasion mechanisms, for example, by inducing over-expression of the
fragment crystallizable gamma receptor IIb (FcγRIIB) receptor on macrophages. High levels of
IgG4 could activate this inhibitory receptor (when the same cell is co-engaged with an activating
FcγR receptor), inducing a state of anergy or even apoptosis of effector cells. It is hypothesized
that IgG4 antibodies, by engaging FcγRIIB receptors located on macrophages can also impair
anti-tumor responses, thus reducing their phagocytic functions.
Class switch toward noninflammatory, spike-specific IgG4 antibodies after
repeated SARS-CoV-2 mRNA vaccination
https://www.science.org/doi/10.1126/sciimmunol.ade2798
RNA vaccines are efficient preventive measures to combat the severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) pandemic. High levels of neutralizing SARS-CoV-2 antibodies are an
important component of vaccine-induced immunity. Shortly after the initial two mRNA vaccine
doses, the immunoglobulin G (IgG) response mainly consists of the proinflammatory subclasses
IgG1 and IgG3. Here, we report that several months after the second vaccination, SARS-
CoV-2–specific antibodies were increasingly composed of noninflammatory IgG4, which were
further boosted by a third mRNA vaccination and/or SARS-CoV-2 variant breakthrough
infections. IgG4 antibodies among all spike-specific IgG antibodies rose, on average, from
0.04% shortly after the second vaccination to 19.27% late after the third vaccination. This
induction of IgG4 antibodies was not observed after homologous or heterologous SARS-CoV-2
vaccination with adenoviral vectors. Single-cell sequencing and flow cytometry revealed substantial
frequencies of IgG4-switched B cells within the spike-binding memory B cell population [median
of 14.4%; interquartile range (IQR) of 6.7 to 18.1%] compared with the overall memory B cell
repertoire (median of 1.3%; IQR of 0.9 to 2.2%) after three immunizations. This class switch was
associated with a reduced capacity of the spike-specific antibodies to mediate antibody-dependent
cellular phagocytosis and complement deposition. Because Fc-mediated effector functions are
critical for antiviral immunity, these findings may have consequences for the choice and
timing of vaccination regimens using mRNA vaccines, including future booster immunizations
against SARS-CoV-2.
The appearance of anti-spike receptor binding domain immunoglobulin G4
responses after repetitive immunization with messenger RNA-based COVID-19
vaccines
https://pubmed.ncbi.nlm.nih.gov/38029832/
The seropositivity of anti-RBD IgG4 after the vaccination was 6.76% at 1 month after the second
dose, gradually increased to 50.5% at 6 months after the second dose, and reached 97.2% at 1
month after the third dose. The seropositivity and titers of anti-RBD IgG1/IgG3 quickly reached
the maximum at 1 month after the second dose and declined afterward.
Repeated vaccinations induce delayed but drastic increases in anti-RBD IgG4 responses. Further
functional investigations are needed to reveal the magnitude of the high contribution of spike-
specific IgG4 subclasses after repeated mRNA-based COVID-19 vaccinations.
Conclusion
The majority of the journals which have covered this particular subject state that there is little
research on the subject and more needs to be done especially in light of the amount of inoculations
given worldwide from 2021. There has been a drastic increase in the people who have autoimmune
conditions and cancer and while it would not be objective to associate these solemnly with the
Covid-19 mRNA vaccine, the medical research is providing a strong link which warrants a much
deeper investigation but only conducted free from conflict of interest and interlocks with the
pharmaceutical industry.
I would like to see this issue raised in Parliament and something tangible be carried out rather than
dismissed as controversial. It is the very least the public deserve to have a thorough investigation
into the matter with transparency especially because these products still continue to be given to this
day and are claimed to be completely safe.
Understandably this is a contentious issue but I believe that through reasonable debate and avenues
for testing set up to find out who may have been harmed we can help restore the public’s trust in the
health services instead of the current situation which is spiralling ever more out of control as the
days go by and the ubiquitous silence of the establishment continues.