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) and 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 above 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 antibodies5 (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 study7
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 paper9
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.
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 study11
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 paper12
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 findings14
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 review15
“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.”
![Mechanism of ADE and antibody mediated immunopathology]()
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 data17,18,19
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.”
