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by Dr. Joseph Mercola
November 11,
2020
from
Mercola Website
Story at-a-glance
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According to a study that examined how informed consent
is given to COVID-19 vaccine trial participants,
disclosure forms fail to inform volunteers that the
vaccine might make them susceptible to more severe
disease if they're exposed to the virus
-
Previous coronavirus vaccine efforts - including those
for SARS, MERS and RSV - have revealed a serious
concern: The vaccines have a tendency to trigger
antibody-dependent enhancement (ADE)
-
ADE
means that rather than enhance your immunity against the
infection, the vaccine actually enhances the virus'
ability to enter and infect your cells, resulting in
more severe disease than had you not been vaccinated
-
Lethal Th2 immunopathology is another potential risk. A
faulty T cell response can trigger allergic
inflammation, and poorly functional antibodies that form
immune complexes can activate the complement system,
resulting in airway damage
-
There's evidence showing the elderly - who are most
vulnerable to severe COVID-19 and would need the vaccine
the most - are also the most vulnerable to ADE and Th2
immunopathology
According to a study that examined how informed consent is given to
COVID-19 vaccine trial participants, disclosure forms fail to inform
volunteers that the vaccine might make them susceptible to more
severe disease if they're exposed to the virus.
The study, 1 "Informed Consent Disclosure to Vaccine
Trial Subjects of Risk of COVID-19 Vaccine Worsening Clinical
Disease," published in the International Journal of Clinical
Practice, October 28, 2020, points out that,
"COVID-19 vaccines
designed to elicit neutralizing antibodies may sensitize vaccine
recipients to more severe disease than if they were not
vaccinated."
"Vaccines for SARS, MERS and RSV have never been approved, and
the data generated in the development and testing of these
vaccines suggest a serious mechanistic concern:
that vaccines
designed empirically using the traditional approach
(consisting of the unmodified or minimally modified
coronavirus viral spike to elicit neutralizing antibodies),
be they composed of protein, viral vector, DNA or RNA and
irrespective of delivery method, may worsen COVID-19 disease
via antibody-dependent enhancement (ADE),
...the paper states."
"This risk is sufficiently obscured in clinical trial protocols
and consent forms for ongoing COVID-19 vaccine trials that
adequate patient comprehension of this risk is unlikely to
occur, obviating truly informed consent by subjects in these
trials.
The specific and significant COVID-19 risk of ADE should have
been and should be prominently and independently disclosed to
research subjects currently in vaccine trials, as well as those
being recruited for the trials and future patients after vaccine
approval, in order to meet the medical ethics standard of
patient comprehension for informed consent."
What Is
Antibody-Dependent Enhancement?
As noted by the authors of that International Journal of Clinical
Practice paper, previous coronavirus vaccine efforts for,
-
severe acute
respiratory syndrome coronavirus (SARS-CoV)
-
Middle East
respiratory syndrome coronavirus (MERS-CoV)
-
respiratory
syncytial virus (RSV),
...have revealed a
serious concern:
The vaccines have a
tendency to trigger antibody-dependent enhancement...
What exactly does that
mean?
In a nutshell,
it means
that rather than enhance your immunity against the infection, the
vaccine actually enhances the virus' ability to enter and infect
your cells, resulting in more severe disease than had you not been
vaccinated. 2
This is the exact opposite of what a vaccine is supposed to do, and
a significant problem that has been pointed out from the very
beginning of this push for a COVID-19 vaccine.
The 2003 review paper
"Antibody-Dependent Enhancement of Virus Infection and Disease"
explains it this way: 3
"In general,
virus-specific antibodies are considered antiviral and play an
important role in the control of virus infections in a number of
ways.
However, in some
instances, the presence of specific antibodies can be beneficial
to the virus. This activity is known as antibody-dependent
enhancement (ADE) of virus infection.
The ADE of virus infection is a phenomenon in which
virus-specific antibodies enhance the entry of virus, and in
some cases the replication of virus, into monocytes/macrophages
and granulocytic cells through interaction with Fc and/or
complement receptors.
This phenomenon has been reported in vitro and in vivo for
viruses representing numerous families and genera of public
health and veterinary importance.
These viruses share
some common features such as preferential replication in
macrophages, ability to establish persistence, and antigenic
diversity.
For some viruses, ADE
of infection has become a great concern to disease control by
vaccination."
Previous
Coronavirus Vaccine Efforts Have All Failed
In my May 2020 interview with Robert Kennedy Jr., he
summarized the history of coronavirus vaccine development, which
began in 2002, following three consecutive SARS outbreaks.
By 2012, Chinese,
American and European scientists were working on SARS vaccine
development, and had about 30 promising candidates.
Of those, the four best vaccine candidates were then given to
ferrets, which are the closest analogue to human lung infections.
In
the video below, which is a select outtake from my full interview,
Kennedy explains what happened next.
While the ferrets
displayed robust antibody response, which is the metric used for
vaccine licensing, once they were challenged with the wild virus,
they all became severely ill and died.
The same thing happened when they tried to develop an RSV vaccine in
the 1960s. RSV is an upper respiratory illness that is very similar
to that caused by coronaviruses.
At that time, they had
decided to skip animal trials and go directly to human trials.
"They tested it on I
think about 35 children, and the same thing happened," Kennedy
said.
"The children
developed a champion antibody response - robust, durable.
It looked perfect
[but when] the children were exposed to the wild virus, they all
became sick. Two of them died. They abandoned the vaccine.
It was a big
embarrassment to FDA and NIH."
Neutralizing
Versus Binding Antibodies
Coronaviruses produce not just one but two different types of
antibodies:
-
Neutralizing
antibodies, 4 also referred to as immoglobulin G
(IgG) antibodies, that fight the infection
-
Binding
antibodies 5 (also known as nonneutralizing
antibodies) that cannot prevent viral infection
Instead of preventing
viral infection, binding antibodies trigger an abnormal immune
response known as "paradoxical immune enhancement."
Another way to look at
this is,
your immune system is actually backfiring and not
functioning to protect you but actually making you worse...
Many of the COVID-19 vaccines currently in the running are using
mRNA to instruct your cells to make the SARS-CoV-2 spike protein (S
protein).
The
spike protein, which
is what attaches to the ACE2 receptor of the cell, is the first
stage of the two-stage process viruses use to gain entry into cells.
The idea is that by creating the SARS-CoV-2 spike protein, your
immune system will commence production of antibodies, without making
you sick in the process.
The key question is,
which of the two
types of antibodies are being produced through this process?
Without
Neutralizing Antibodies, Expect More Severe Illness
In an April 2020 Twitter thread, 6 The Immunologist
noted:
"While developing
vaccines... and considering immunity passports, we must first
understand the complex role of antibodies in SARS, MERS and
COVID-19."
He goes on to list
several coronavirus vaccine studies that have raised concerns about
ADE.
The first is a 2017 study 7 in PLOS Pathogens, "Enhanced
Inflammation in New Zealand White Rabbits When MERS-CoV Reinfection
Occurs in the Absence of Neutralizing Antibody," which investigated
whether getting infected with MERS would protect the subject against
reinfection, as is typically the case with many viral illnesses.
(Meaning, once you
recover from a viral infection, say measles, you're immune and won't
contract the illness again.)
To determine how MERS affects the immune system, the researchers
infected white rabbits with the virus. The rabbits got sick and
developed antibodies, but those antibodies were not the neutralizing
kind, meaning the kind of antibodies that block infection.
As a result, they were
not protected from reinfection, and when exposed to MERS for a
second time, they became ill again, and more severely so.
"In fact, reinfection
resulted in enhanced pulmonary inflammation, without an
associated increase in viral RNA titers," the authors noted.
Interestingly,
neutralizing antibodies were elicited during this second infection,
preventing the animals from being infected a third time.
According to the authors:
"Our data from the
rabbit model suggests that people exposed to MERS-CoV who fail
to develop a neutralizing antibody response, or persons whose
neutralizing antibody titers have waned, may be at risk for
severe lung disease on re-exposure to MERS-CoV."
In other words,
if the
vaccine does not result in a robust response in neutralizing
antibodies, you might be at risk for more severe lung disease if
you're infected with the virus....
And here's an important point:
COVID-19 vaccines are NOT designed to
prevent infection...
As detailed in "How COVID-19 Vaccine Trials Are
Rigged," a "successful" vaccine merely needs to reduce the severity
of the symptoms.
They're not even
looking at reducing infection,
hospitalization or death rates...
ADE in Dengue
Infections
The Dengue virus is also known to cause ADE.
As explained in a Swiss
Medical Weekly paper published in April 2020: 8
"The pathogenesis of
COVID-19 is currently believed to proceed via both directly
cytotoxic and immune-mediated mechanisms.
An additional
mechanism facilitating viral cell entry and subsequent damage
may involve the so-called antibody-dependent enhancement (ADE).
ADE is a very well-known cascade of events whereby viruses may
infect susceptible cells via interaction between virions
complexed with antibodies or complement components and,
respectively, Fc or complement receptors, leading to the
amplification of their replication.
This phenomenon is of enormous relevance not only for the
understanding of viral pathogenesis, but also for developing
antiviral strategies, notably vaccines...
There are four serotypes of Dengue virus, all eliciting
protective immunity. However, although homotypic protection is
long-lasting, cross-neutralizing antibodies against different
serotypes are short-lived and may last only up to 2 years.
In Dengue fever, reinfection with a different serotype runs a
more severe course when the protective antibody titer wanes.
Here,
non-neutralizing antibodies take over neutralizing ones, bind to
Dengue virions, and these complexes mediate the infection of
phagocytic cells via interaction with the Fc receptor, in a
typical ADE.
In other words, heterotypic antibodies at subneutralizing titres
account for ADE in persons infected with a serotype of Dengue
virus that is different from the first infection.
Cross-reactive neutralizing antibodies are associated with
decreased odds of symptomatic secondary infection, and the
higher the titer of such antibodies following the primary
infection, the longer the delay to symptomatic secondary
infection..."
The paper goes on to
detail results from follow-up investigations into the Dengue
vaccine, which revealed the hospitalization rate for Dengue among
vaccinated children under the age of 9 was greater than the rate
among controls.
The explanation for this
appears to be that the vaccine mimicked a primary infection, and as
that immunity waned, the children became susceptible to ADE when
they encountered the virus a second time.
The author explains:
"A post hoc analysis
of efficacy trials, using an anti-nonstructural protein 1
immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA)
to distinguish antibodies elicited by wild-type infection from
those following vaccination, showed that the vaccine was able to
protect against severe Dengue [in] those who had been exposed to
the natural infection before vaccination, and that the risk of
severe clinical outcome was increased among seronegative
persons.
Based on this, a Strategic Advisor Group of Experts convened by
World Health Organization (WHO) concluded that only
Dengue seropositive persons should be vaccinated whenever Dengue
control programs are planned that include vaccination."
ADE in
Coronavirus Infections
This could end up being important for the COVID-19 vaccine.
Hypothetically speaking,
if SARS-CoV-2 works like Dengue, which is also caused by an RNA
virus, then anyone who has not tested positive for SARS-CoV-2 might
actually be at increased risk for severe COVID-19 after vaccination,
and only those who have already recovered from a bout of COVID-19
would be protected against severe illness by the vaccine.
To be clear,
we do not know
whether that is the case or not, but these are important areas
of inquiry and the current vaccine trials will simply not be
able to answer this important question.
The Swiss Medical Weekly
paper 9 also reviews the evidence of ADE in coronavirus
infections, citing research showing inoculating cats against the
feline infectious peritonitis virus (FIPV) - a feline coronavirus -
increases the severity of the disease when challenged with the same
FIPV serotype as that in the vaccine.
Experiments have shown
immunization
with a variety of SARS vaccines
resulted in
pulmonary immunophathology
once challenged
with the SARS virus.
The paper also cites research showing,
"Antibodies elicited
by a SARS-CoV vaccine enhanced infection of B cell lines in
spite of protective responses in the hamster model."
Another paper, 10
"Antibody-Dependent SARS Coronavirus Infection Is Mediated by
Antibodies Against Spike Proteins," published in 2014, found that:
"… higher
concentrations of anti-sera against SARS-CoV neutralized
SARS-CoV infection, while highly diluted anti-sera significantly
increased SARS-CoV infection and induced higher levels of
apoptosis.
Results from infectivity assays indicate that SARS-CoV ADE is
primarily mediated by diluted antibodies against envelope spike
proteins rather than nucleocapsid proteins.
We also generated
monoclonal antibodies against SARS-CoV spike proteins and
observed that most of them promoted SARS-CoV infection.
Combined, our results suggest that antibodies against SARS-CoV
spike proteins may trigger ADE effects. The data raise new
questions regarding a potential SARS-CoV vaccine..."
A study 11 that ties into this was published in the
journal JCI Insight in 2019.
Here, macaques
vaccinated with a modified vaccinia Ankara (MVA) virus encoding
full-length SARS-CoV spike protein ended up with more severe
lung pathology when the animals were exposed to the SARS virus.
And, when they
transferred anti-spike IgG antibodies into unvaccinated
macaques, they developed acute diffuse alveolar damage, likely
by "skewing the inflammation-resolving response."
SARS Vaccine
Worsens Infection After Challenge With SARS-CoV
An interesting 2012 paper 12 with the telling title,
"Immunization with SARS Coronavirus Vaccines Leads to Pulmonary
Immunopathology on Challenge with the SARS Virus," demonstrates what
many researchers now fear, namely,.
that COVID-19
vaccines may end up making people more prone to severe
SARS-CoV-2 infection...
The paper reviews
experiments showing immunization with a variety of SARS vaccines
resulted in pulmonary immunophathology once challenged with the SARS
virus.
As noted by the authors:
13
"Inactivated whole
virus vaccines whether inactivated with formalin or beta
propiolactone and whether given with our without alum adjuvant
exhibited a Th2-type immunopathologic in lungs after challenge.
As indicated, two reports attributed the immunopathology to
presence of the N protein in the vaccine; however, we found the
same immunopathologic reaction in animals given S protein
vaccine only, although it appeared to be of lesser intensity.
Thus, a Th2-type immunopathologic reaction on challenge of
vaccinated animals has occurred in three of four animal models
(not in hamsters) including two different inbred mouse strains
with four different types of SARS-CoV vaccines with and without
alum adjuvant.
An inactivated
vaccine preparation that does not induce this result in mice,
ferrets and nonhuman primates has not been reported.
This combined experience provides concern for trials with
SARS-CoV vaccines in humans. Clinical trials with SARS
coronavirus vaccines have been conducted and reported to induce
antibody responses and to be 'safe.'
However, the evidence
for safety is for a short period of observation.
The concern arising from the present report is for an
immunopathologic reaction occurring among vaccinated individuals
on exposure to infectious SARS-CoV, the basis for developing a
vaccine for SARS.
Additional safety
concerns relate to effectiveness and safety against antigenic
variants of SARS-CoV and for safety of vaccinated persons
exposed to other coronaviruses, particularly those of the type 2
group."
The Elderly
Are Most Vulnerable to ADE
On top of all of these concerns, there's evidence showing the
elderly - who are most vulnerable to severe COVID-19 - are also the
most vulnerable to ADE.
Preliminary research
findings 14 posted on the preprint server medRxiv at the
end of March 2020 reported that middle-aged and elderly COVID-19
patients have far higher levels of anti-spike antibodies - which,
again, increase infectivity - than younger patients.
Immune
Enhancement Is a Serious Concern
Another paper worth mentioning is the May 2020 mini review 15
"Impact of Immune Enhancement on COVID-19 Polyclonal Hyperimmune
Globulin Therapy and Vaccine Development."
As in many other papers,
the authors point out that: 16
"While development of
both hyperimmune globulin therapy and vaccine against SARS-CoV-2
are promising, they both pose a common theoretical safety
concern.
Experimental studies
have suggested the possibility of immune-enhanced disease of
SARS-CoV and MERS-CoV infections, which may thus similarly occur
with SARS-CoV-2 infection...
Immune enhancement of disease can theoretically occur in two
ways. Firstly, non-neutralizing or sub-neutralizing levels of
antibodies can enhance SARS-CoV-2 infection into target cells.
Secondly, antibodies could enhance inflammation and hence
severity of pulmonary disease. An overview of these antibody
dependent infection and immunopathology enhancement effects are
summarized in Fig. 1...
Currently, there are multiple SARS-CoV and MERS-CoV vaccine
candidates in pre-clinical or early phase clinical trials.
Animal studies on
these CoVs have shown that the spike (S) protein-based vaccines
(specifically the receptor binding domain, RBD) are highly
immunogenic and protective against wild-type CoV challenge.
Vaccines that target other parts of the virus, such as the
nucleocapsid, without the S protein, have shown no protection
against CoV infection and increased lung pathology.
However, immunization
with some S protein based CoV vaccines have also displayed signs
of enhanced lung pathology following challenge.
Hence, besides the choice of antigen target, vaccine efficacy
and risk of immunopathology may be dependent on other ancillary
factors, including adjuvant formulation, age at vaccination...
and route of immunization."
Figure 1:
Mechanism of ADE and antibody mediated immunopathology.
Left panel: For ADE, immune complex internalization is mediated by
the engagement of activating Fc receptors on the cell surface.
Co-ligation of inhibitory receptors then results in the inhibition
of antiviral responses which leads to increased viral replication.
Right panel: Antibodies can cause immunopathology by activating
the complement pathway or antibody-dependent cellular cytotoxicity (ADCC).
For both pathways, excessive immune activation
results in the release of cytokines and chemokines,
leading to enhanced disease pathology.
Do a
Risk-Benefit Analysis Before Making Up Your Mind
In all likelihood, regardless of how effective (or ineffective) the
COVID-19 vaccines end up being, they'll be released to the public in
relatively short order.
Most predict one or more
vaccines will be ready sometime in 2021.
Ironically, the data 17,18,19 we now have no longer
support a mass vaccination mandate, considering the lethality of
COVID-19 is lower than the flu for those under the age of 60.
20
If you're under the age
of 40, your risk of dying from COVID-19 is just 0.01%, meaning you
have a 99.99% chance of surviving the infection. And you could
improve that to 99.999% if you're metabolically flexible and vitamin
D replete.
So, really, what are we protecting against with
a COVID-19 vaccine?
As mentioned, the
vaccines aren't even designed to prevent infection, only reduce the
severity of symptoms. Meanwhile, they could potentially make you
sicker once you're exposed to the virus.
That seems like a lot of
risk for a truly questionable benefit.
To circle back to where we started, participants in current COVID-19
vaccine trials are not being told of this risk - that by getting the
vaccine they may end up with more severe COVID-19 once they're
infected with the virus.
Lethal Th2
Immunopathology Is Another Potential Risk
In closing, consider what this PNAS news feature states about the
risk of vaccine-induced immune enhancement and dysfunction,
particularly for the elderly, the very people who would need the
protection a vaccine might offer the most: 21
"Since the 1960s,
tests of vaccine candidates for diseases such as dengue,
respiratory syncytial virus (RSV), and severe acute respiratory
syndrome (SARS) have shown a paradoxical phenomenon:
Some animals or people who received the vaccine and were later
exposed to the virus developed more severe disease than those
who had not been vaccinated.
The vaccine-primed
immune system, in certain cases, seemed to launch a shoddy
response to the natural infection...
This immune backfiring, or so-called immune enhancement, may
manifest in different ways such as antibody-dependent
enhancement (ADE), a process in which a virus leverages
antibodies to aid infection; or cell-based enhancement, a
category that includes allergic inflammation caused by
Th2
immunopathology.
In some cases, the enhancement processes might
overlap...
Some researchers argue that although ADE has received the most
attention to date, it is less likely than the other immune
enhancement pathways to cause a dysregulated response to
COVID-19, given what is known about the epidemiology of the
virus and its behavior in the human body.
'There is the
potential for ADE, but the bigger problem is probably Th2
immunopathology,' says Ralph Baric, an epidemiologist and
expert in coronaviruses... at the University of North
Carolina at Chapel Hill.
In previous studies
of SARS, aged mice were found to have particularly high risks of
life-threatening Th2 immunopathology... in which a faulty T cell
response triggers allergic inflammation, and poorly functional
antibodies that form immune complexes, activating the complement
system and potentially damaging the airways."
Sources and
References
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