October 28,
2022
By Geert Vanden Bossche
On rare occasions I read some vaccine talk produced
by mainstream journalists. It is interesting to see how in light of the
continuing series of disappointing vaccine experiments on humans they
cautiously begin to balance their remaining critical thinking faculties with
the mainstream narrative that dominated their views for so long. The recent
article: ‘Updated Covid-19 vaccines boost protection, but may not beat
original formula against BA.4 and BA.5, early studies suggest ‘ is one
such marvelous
example.(https://edition.cnn.com/2022/10/26/health/updated-boosters-omicron-imprint/index.html)
Since I am much better at mastering the science
than I am the language, I am going to provide science-based critiques to the
big gaps in the immunological interpretation of the data reported on the first
bivalent booster studies. I’ll share my comments to the cited interpretations
of leading scientists and experts, however I’ll refrain from citing their names
as I have no intention to ridicule these individuals—I only intend to point out
the immunological ignorance of those still officially referred to as
acknowledged key opinion leaders and decision makers in the field. Their
immunological ignorance is now inspiring further efforts to fight evil (mass
vaccination) with more evil (mass vaccination with updated vaccines)—a recipe
for disaster that will certainly end the pandemic the ‘hard’ way. Nature will
ultimately teach them how immunology works, and unfortunately not before
massive damage is inflicted by the mass vaccination experiment. Before I get to
the specific comments uttered by our leading ‘experts’ and cited within this
article, I’ll open with a mind-boggling statement made by the journalist to
first give a “masterclass” of softs in immunology to these very leading
‘experts’:
“But the hope was that by tweaking the vaccine
recipe to include currently circulating strains of theOmicron variant, it would
help broaden immunity against those variants and perhaps offer better and
longer-lasting protection”
Geert (G): How can one conduct experiments on
humans just based on some naïve ‘hope’? Why do scientists produce extensive
data on deep mutational scanning without investigating the immunological driver
behind the patterns of such reported mutations? If they would only do so, they
would immediately realize the abundance of scientific rationale that could
substitute for all the hope they put in empirical research on humans.
The scientific evidence clearly indicates that no
single updated/ adapted vaccine booster will improve the temporary protective
effect conferred by the Wuhan-Hu S-based C-19 vaccines but will instead only
expedite immune escape.
Why?
Meanwhile, a myriad of reports documenting the
convergent mutations in steadily evolving SARS-CoV-2(SC-2) variants
unambiguously illustrates that both productive vaccine breakthrough infections
and mRNA vaccine-based boosters place immune pressure on more conserved, immune
subdominant spike (S)-associated epitopes by recalling immature memory B cells
that produce low affinity antibodies (Abs).Of course, the resulting suboptimal
pressure exerted by these Abs on these more conserved antigenic domains drives
immune escape, first away from the recalled broadly neutralizing (i.e.,
variant-nonspecific) Abs and subsequently from the broadly infection-inhibiting
Abs. This is due to ‘immune refocusing’, a phenomenon that occurs when
pre-existing Abs bind to their pathogen-associated target epitopes with low
affinity (i.e., not allowing virus neutralization in case of SC-2, for
example): see fig.attached at the bottom. In this way, previously
immunodominant epitopes expressed on the free-circulating antigen (e.g., spike
protein in case of SC-2) can no longer be recognized by the host immune system
whereas previously outcompeted antigenic determinants comprised within the same
antigen but expressed on infected or transfected target cells will take
advantage of the masking effect to recall the corresponding previously primed
Abs.
The existence of previously primed ‘mismatching’
Abs is quite obvious in case of breakthrough infections, but how does this
occur in case of mRNA booster vaccines?
It suffices to understand that internalization of
secreted in vivo synthesized S protein into antigen-presenting
cells (APCs) will provide cognate and noncognate T help to immunodominant
epitopes on the free-circulating S protein and S
protein expressed at the surface of the mRNA-transfected target cells, respectively.
Abs to the latter have therefore much lower affinity and are the first to be
recalled upon the administration of mRNA vaccine booster doses. As they will
subsequently bind (with low affinity) to the immunodominant determinants on the
free circulating S protein (i.e., once the latter is released from the
mRNA-transfected cell), the subdominant antigenic determinants will be able to
outcompete the immunodominant epitopes for assistance from memory T helper
cells (recalled as a result of internalization of S protein into APCs) to
recall their corresponding, broadly cross-functional memory Bcells. The
neutralizing anti-S Abs (NAbs) recalled as a result of the original Wuhan-Hu
spike memory(i.e., the ‘hidden’ original antigenic sin) imprinted by the mRNA
vaccine have low affinity and are directed at conserved but less immunogenic
S-associated domains. So, repeated boosting with mRNA-based vaccines will
merely drive the immune system to repeat commitment of the ‘hidden’ antigenic
sin. Consequently, mRNA booster injections will expedite immune escape by
enabling immune refocusing to be repeated. As illustrated in the figure
attached at the bottom, immune refocusing subsequently triggers the elicitation
of low affinity infection-inhibiting Abs targeted at more conserved domains.
So, regardless of the S version comprised in the mRNA vaccines, the
mRNA booster vaccine doses facilitate humoral immune pressure on shared (i.e.,
variant-nonspecific) antigenic domains that contribute to viral neutralizability
and infectiousness. Massive mRNA booster campaigns will therefore
accelerate immune escape long before enhanced maturation of the recalled,
poorly matured memory Bcells takes place in germinal centers (as equally
described in several recent publications).
As mRNA boosters (as well as vaccine breakthrough infections) facilitate immune
pressure on variant-nonspecific domains, the type of immune escape they
indirectly promote is no longer determined by specific characteristics of the
dominantly circulating SC-2 variant. This explains why we’re now witnessing
more and more NAb-resistant, highly infectious variants co-circulating in
the population.Lastly, as immune refocusing shifts the immune response to
conserved domains with very different antigenic characteristics, it is not
surprising that ‘mutation spotters’ consider the mutations to reflect ‘large
scale’ immune escape.
End of master class...
Here come the expert interpretations or cited
comments followed by my critique:
“Immunologists say a vaccine against two strains
may not be better than a single strain shot because of a phenomenon called
immune imprinting”
G: These immunologists are confusing ‘immune imprinting’ or ‘antigenic sin’
with ‘immune refocusing’. If immune imprinting was responsible for the
protective effect observed, one would expect improved protection (even if only
short-lived) after the booster dose. This is not the case as each new
additional booster has become less and less effective.
“Scientists say imprinting may complicate efforts to
stay ahead of new variants as the coronavirus continues to evolve, and it adds
urgency to the development of new vaccine technologies to fight the virus” or:
“We may need different kinds of vaccine technologies if the virus ever changes
so much that it outcompetes our immunity altogether”
G: These scientists don’t seem to realize that the virus only needs about
12 hours to put a new generation (and hence, new immune escape variants to
select from) on the globe. What are the new technologies they’re alluding to?
They haven’t yet advanced any scientifically sound approach to a universal
Coronavirus (CoV) or Sarbecovirus vaccine. Is it so difficult to understand
that performing mass vaccination with any kind of CoV vaccine during a pandemic
will drive immune escape? Adaptive immune effector cells (typically those
vaccines are relying upon to protect) need time to mature and reach sufficient
affinity to have optimal neutralizing capacity. Perhaps they were they thinking
of ‘mucosal’ immunization? Regardless, the latter will never solve the issue of
immune escape either when administered during a pandemic.
“When the US Food and Drug Administration issued
emergency use authorizations for new bivalentCovid-19 vaccines from Pfizer and
Moderna at the end of August, it did so on the basis of studies in mice and
previous human trials with a different two-strain booster formulation. Little
was known about the how protective the shots might be in people; full data from
clinical trials testing the BA.4 and BA.5bivalent vaccines in humans hasn’t yet
been made public. But modeling data suggested that getting the boosters out in
September could save tens of thousands of lives....”
G: It is simply unbelievable that experts and regulatory folks largely rely
on mice data to conduct new experiments on humans using yet another mRNA
vaccine! Have those working for decades in this field not yet learned that mice
lie, especially when it comes to immunizing animals with an immunological
background that is not comparable to that of the target human population? And
when will all these computational scientists and mathematicians finally learn
that a model is only as good as its assumptions? As they clearly don’t
understand the immunology involved, their assumptions are always wrong and so
too are the results of their modeling.
“We can’t say that a few months from now, there
won’t be any difference,” he said. “We won’t know that until these individuals
are followed for a longer period of time.”
“Clinical trials being conducted by vaccine makers
Pfizer and Moderna involve hundreds of people who have had the updated boosters
and are being followed for longer periods of time. Data from those studies are
still coming”.
G: Clearly, this scientist/ doctor is alluding to the maturation of the
elicited memory B cells that has now been repeatedly reported to result from
breakthrough infections or booster shots. However, it has been convincingly
documented that this maturation process takes several months (4-6 months)
before accomplishing full-fledged affinity maturation. Again, the virus is not
waiting for this to happen. By the time this occurs the virus will long since
have accomplished additional immune escape operations, especially when immune
pressure is exerted at a population level.
“...the researchers found that neutralizing
antibodies spiked after both shots to about the same high levels, which was
good news”
G: Oh really? Why would this be good news knowing that the only effect of
these Abs is to drive immune refocusing which triggers large scale immune
escape? How many times must I state that if there is one rule that doesn’t
apply to immunology it is that more is not always better (in fact, the opposite
usually applies)
“Unfortunately, neither one increased T-cell
responses very much, and we believe that T-cell responses in addition to
antibody responses are important for protection against severe disease,”
G: Some of the top researchers doggedly continue to preach the power of
cross-reactive T cells in controlling the virus and taming the pandemic. They
seem to have little understanding of the pathobiology and immunology involved
in acute SELF-LIMITING viral infections. Maybe some of themare confused by too
much HIV vaccine research?
Once again, I am citing just a few of the many
articles I’ve written to debunk the critical role of T cells in protecting
against SC-2 infection/ disease:
# When anti-S(pike) antibodies against Omicron can
no longer sustain the narrative, why not resort to T cells?
https://www.voiceforscienceandsolidarity.org/scientific-blog/when-anti-s-pike-antibodies-against-omicron-can-no-longer-sustain-the-narrative-why-not-resort-to-t-cells
# Q&A #09: Do cross-reactive T cells explain
mild course of Omicron infection?
https://www.voiceforscienceandsolidarity.org/scientific-blog/q-a-09-do-cross-reactive-t-cells-explain-mild-course-of-omicron-infection
# To all those who continue to attribute abrogation
of SARS-CoV-2 infection to pre-existing cross-reactive T cells rather than to
innate immunity. The devil is in the detail of peer-reviewed publications.
https://www.voiceforscienceandsolidarity.org/scientific-blog/to-those-who-continue-attribute-abrogation-sars-cov-2-infection-pre-existing-cross-reactive-t-cells-rather-innate-immunity-the-devil-is-the-detail
# Cross-reactive memory T cells are associated with
(but not responsible for) protection againstSARS-CoV-2 infection in COVID-19
contacts.
https://www.voiceforscienceandsolidarity.org/scientific-blog/cross-reactive-memory-t-cells-are-associated-with-but-not-responsible-for-protection-against-sars-cov-2-infection-in-covid-19-contacts
# ‘Killer’ immune cells still recognize Omicron
variant.... oh really?
https://www.voiceforscienceandsolidarity.org/scientific-blog/killer-immune-cells-still-recognize-omicron-variant-oh-really
“A booster is a booster until proven otherwise and
we are in great need of getting more of them in theUS”
G: Yes, and a vaccine is a vaccine until proven otherwise, correct??! This
scientist/ doctor seems to be areal fanatic of the concept: the more, the
better (i.e., the higher the Ab titers and the more boosters,the better)
without asking himself about the immunological mechanism triggered by the
boosted Absand the longer-term effects thereof.
“I would be lying to you if [I said] it doesn’t
keep me up at night worrying that there is a certain chancethat we may have to
deploy another booster – at least for a portion of the population, perhaps
olderindividuals – before next September, October,”
G: It seems to me that many regulators would be better off spending their
sleepless nights on trying toput the pieces of the immunological puzzle
together (or listening to others?!) instead of complainingabout their inability
to answer the obvious questions that keep them up at night....
“Both new studies have limitations, but I think
when you put them together, they paint a pretty clearpicture that that
antigenic imprinting is causing issues here, for sure.” “That’s the reason some
strains ofthe flu may hit certain age groups harder than others, too. When viruses
look more similar to the firstinfection or vaccine you had, your body tends to
do a better job fighting them off.”
”It probably would have been better to update the
vaccine by including only the components againstBA.4 and BA.5.” or: “For me,
the take-home message is, if you want to boost and provide protection against
Omicron, leave the original variant out of the vaccine.” Or: “Imprinting will
complicate efforts to keep up with the virus”
G: Given the fact that ‘immune imprinting’ or ‘original antigenic sin’ is
one of the oldest and irrefutable paradigms in immunology, why was the
ancestral S version made part of the bivalent booster formulations in the first
place? But as I explained before, it wouldn’t have made any difference as any
version of mRNA-based S protein will entail immune refocusing to other (i.e.,
subdominant) epitopes.Immune refocusing implies immune imprinting (i.e.,
‘hidden’ antigenic sin) but not the other way around.
“It’s possible to break through immune imprinting.
Certain kinds of vaccine ingredients, or adjuvants –things that just happen to
really wake up the immune system – can do it.”
G: This fellow has forgotten about one key principle in vaccinology: The
vaccine is only as good as the antigen! Of course, adjuvants can increase the
magnitude and breadth of the immune response, but this will not influence
noncognate Th-dependent priming of low affinity Abs to spike protein because
the latter are directed against membrane-bound spike protein which is de
facto not internalized into APCs, which is a conditio sine
qua non for putting adjuvants at work!
Conclusion: Given the deep immunological incompetence of our leading scientific,
public health and regulatory experts, one can easily predict that there will be
many more plans for empiricism and injecting yet other experimental
formulations than there are lucid brains. We should not forget, though, that
mankind has never been in control of this pandemic and that this is even less
the case as their rational experimentation continues. Indeed, the more man
mismanages the pandemic by scientifically irrational immune interventions, the
more (and the faster) the virus is evolving towards teaching a lesson in
immunology that will hopefully be remembered by the future generation of
scientists to come.History, however, will not be as mild as I am with the
quotes of those who thought to learn from inconsiderate and dangerous
experiments conducted on humans.
Fig.: Immune
refocusing (IR) occurs when pre-existing Abs bind to their target epitopes with
low affinity (e.g., in case of vaccine breakthrough disease or vaccine boosters
in previously mRNA vaccine-primedpersons). Masking of immunodominant
S(pike)-associated epitopes allows subdominant epitopes tooutcompete the former
for assistance from memory T helper cells. This will enable the subdominant
S-associated epitopes to recall low-affinity Abs directed at these epitopes. By
placing suboptimal immunepressure on these more conserved antigenic domains,
the recalled Abs promote large scale immuneescape. The latter results in
natural selection and dominant propagation of a multitude of
NAb-resistant,highly infectious immune escape SC-2 variants.
Geert Vanden Bossche received his DVM from the
University of Ghent, Belgium, and his PhD degree in Virology from the
University of Hohenheim, Germany. He held adjunct faculty appointments at
universities in Belgium and Germany. After his career in Academia, Geert joined
several vaccine companies (GSK Biologicals, Novartis Vaccines, Solvay
Biologicals) to serve various roles in vaccine R&D as well as in late
vaccine development.
Geert then moved on to join the Bill & Melinda
Gates Foundation’s Global Health Discovery team in Seattle (USA) as Senior
Program Officer; he then worked with the Global Alliance for Vaccines and
Immunization (GAVI) in Geneva as Senior Ebola Program Manager. At GAVI he
tracked efforts to develop an Ebola vaccine. He also represented GAVI in fora
with other partners, including WHO, to review progress on the fight against
Ebola and to build plans for global pandemic preparedness.
Back in 2015, Geert scrutinized and questioned the
safety of the Ebola vaccine that was used in ring vaccination trials conducted
by WHO in Guinea. His critical scientific analysis and report on the data
published by WHO in the Lancet in 2015 was sent to all international health and
regulatory authorities involved in the Ebola vaccination program. After working
for GAVI, Geert joined the German Center for Infection Research in Cologne as
Head of the Vaccine Development Office. He is at present primarily serving as a
Biotech / Vaccine consultant while also conducting his own research on Natural
Killer cell-based vaccines.
Email: info@voiceforscienceandsolidarity.org
Source: https://www.voiceforscienceandsolidarity.org/scientific-blog/the-greatest-enemy-in-the-control-of-the-pandemic-is-the-immunological-ignorance-of-our-leading-scientific-public-health-and-regulatory-experts
