What happens if a pandemic involving a virus naturally causing acute self-limiting infection fails to generate herd immunity?
What-happens-if-a-pandemic-involving-avirus-naturally-causing-acute-self-limiting-infection-fails-to-generate-herd-immunityGeneral considerations
Abbreviations:
Ab: Antibody
APC: Antigen (Ag)-presenting cell
C-19: Covid-19
CII: Cell-based innate immunity
CTL: Cytotoxic T lymphocyte
DC: Dendritic cell
NAb: Neutralizing Ab
NK cell: Natural Killer cell
PNNAB: Polymeric non-neutralizing Ab
RBD: Receptor-binding domain
S: Spike (protein)
SC-2: SARS-CoV-2
SIR: Steric immune refocusing
(V)BTI: (Vaccine) breakthrough infection
A lack of comprehensive understanding of immunology poses a significant hurdle to the development of effective public health interventions and prevention strategies during pandemics.
- Key stakeholders in pandemic management, including epidemiologists, virologists, public health
experts, and authorities, lack profound insights into the adaptive dynamics of the host immune
response that develops during a pandemic. Even the concept of herd immunity isn’t correctly
understood. - Any (large-scale) intervention in population immunity that does not prevent viral transmission
may have catastrophic consequences on public and individual health. The idea that viruses
evolve to become benign — like the coronavirus evolving into the “common cold” — is a “myth”
and was never guaranteed. - Implementing widespread measures to impede viral growth —i.e., viral transmission in the case
of an acute self-limiting viral infection— eventually drives a spectacular gain in viral fitness. This
can manifest as gain in resistance to NAbs in the case of large-scale immune pressure on virus
neutralizability (e.g., Omicron BA.1) or gain in intrinsic viral infectiousness in the case of largescale immune pressure on viral infectiousness (e.g., BA.2.86). - Failure to comprehend the impact of adaptive, population-level immune pressure has resulted
in failure to understand why and how mass vaccination has transformed a natural pandemic
into one marked by more infectious variants.
HERD IMMUNITY
- In the context of acute, self-limiting infections, herd immunity refers to a level of
population-level immunity that reduces the level of (viral) transmission down to a
threshold where individuals who have not been immunized (for lack of exposure to
wild or live attenuated vaccine) are protected against infection. Herd immunity
therefore stops viral spread in the population. - Herd immunity is achieved when a sufficiently large portion of the population
develops sterilizing immunity towards the circulating virus/ pathogen. - No pandemic of an acute, self-limiting viral infection can be contained without herd
immunity! - Due to its self-limiting nature, a pandemic of an acute self-limiting viral infection
can never be considered a health emergency of international concern! - Because the threshold for seroconversion (SC) to attain herd immunity following
natural infection varies based on pre-existing population-level innate immunity and
viral transmissibility, the SC rate is not be a reliable metric for assessing herd
immunity. Conversely, vaccine-induced SC rates are not a reliable metric either as C19 vaccines do not stimulate cell-based innate immunity.
As some so-called ‘experts’ are confounding herd (i.e., population-level) immune pressure
with herd immune protection, they have claimed that the ‘acute phase’ of the pandemic is
over. They don’t seem to understand that when the acute phase of a pandemic involving a
virus causing acute self-limiting infection were over, this would mean that the pandemic is
over altogether!
- As others ignore how adaptive immune responses evolve as a consequence of mass
vaccination, they consider the emergence of Omicron BA.1 and BA.2.86 ‘unnatural’ and rely
on conspiracy theories or scapegoat immune-suppressed individuals to explain the sudden
dominant propagation of these highly mutated, highly transmissible immune escape variants*. - When a virus reaches peak infectiousness while still facing sustained immune pressure on its
transmissibility, it may unleash the brakes on systemic viral dissemination to increase viral
replication and propagation within the host → enhanced viral virulence. - Contrary to being a blessing, Omicron must be considered a scourge, triggering vaccine
breakthrough infections that shift immune responses from suboptimal S variant-specific NAbs
to suboptimal S variant-cross-reactive, infection-inhibiting Abs. This perpetuates a cycle of
suboptimal immune pressure, facilitating ongoing viral immune escape. - As infection-mitigating Abs lose efficacy, Ab-mediated immune pressure increasingly shifts to
CTL-mediated immune pressure.
What you need to know about immune steric refocusing (SIR)
- Immune refocusing is triggered by VBTIs and updated vaccine boosters;
mRNA vaccines promote SIR in their own right, even in the absence of
VBTIs. - Immune refocusing drives immune escape
- Infections with newly emerging variants in C-19 vaccinees inevitably cause
SIR-enabling VBTIs. Highly C-19 vaccinated populations are therefore
driving irreversible viral immune escape. - SIR makes the host immune response not only weaker (less affinity), but
also broader (less specific) and eventually shifts the immune response from
humoral to cell-mediated.
Avidity is a measure of the overall strength and stability of interactions between multiple binding sites on a bivalent or multivalent Ab and its corresponding multivalent Ag. Low-affinity Abs cover a broader scope of variants and can stabilize viral particulates over a broader range of dilutions. These Abs can, therefore, exert much broader and stronger immune selection pressure on viral infectiousness (via their prolonged infectionmitigating activity) compared to high-affinity Abs. At excessively high concentration, though, the latter have much higher pseudo-neutralizing capacity than low-affinity Abs
- CTL-mediated abrogation of viral transmission becomes suboptimal as more infectious
virus increasingly adsorbs to APCs instead of being internalized into these cells. This lowers
the concentration of PNNAbs down to suboptimal levels, thereby leading highly C-19
vaccinated populations to exert immune selection pressure on viral virulence. - Finally, as immune refocusing promotes the recognition of more conserved S-associated B
cell epitopes with degenerate specificity^, VBTIs (and mRNA vaccines!) likely promote an
increased incidence of autoimmune diseases and cancers. - In essence, a comprehensive understanding of immunology is crucial for understanding
that the collective natural immunity within a population (i.e., herd immunity) is the most
effective immune strategy to combat pandemics and avoid the emergence of more
infectious viral variants.
^Flexibility in MHC and TCR Recognition: Degenerate Specificity at the T Cell Level in the Recognition of Promiscuous Th Epitopes Exhibiting No Primary Sequence Homology: https://pubmed.ncbi.nlm.nih.gov/11359825/
And this is how it all started…..and how it is likely to end….
- Large-scale immunization against S protein (responsible for viral infectiousness) during
an acute viral pandemic fails to generate herd immunity and instead generates ‘herd’
immune pressure. - Collective (mass vaccination!), highly selective immune pressure exerted by
‘neutrali ation-mitigating’ A s on the specific immunodominant domain of the
‘infectious’ protein i.e., -RBD) eventually promotes dominant propagation of an
immune escape variant (Omicron) that collectively resists S-specific NAbs (> 30 mutations). - Diminished neutralizing capacity of previously primed Abs promotes production of PNNAbs
(IgMs), thereby triggering PNNAb-dependent VBTIs (https://pubmed.ncbi.nlm.nih.gov/34384810/
The latter restimulate previously vaccine-primed Abs at high titers, thereby triggering SIR,
while PNNAbs inhibit viral trans infectiousness. - SIR leads to boosting of previously primed, broadly cross S variant-reactive B cells, which
produce low-affinity Abs with suboptimal neutralizing capacity. These low-affinity Abs
stably mitigate viral infectiousness while recognition of more conserved S-associated B cell
epitopes with degenerate specificity promotes early onset autoimmune diseases and
cancers (IgG4 Abs) - Suboptimal S variant-nonspecific immune pressure exerted y ‘infection-mitigating’ A s on
viral infectiousness promotes co-circulation of a diversified spectrum of newly emerging,
more infectious immune escape variants, thereby ensuring perpetuation of VBTIs and
immune refocusing. - Collective (large-scale VBTIs), suboptimal immune pressure on viral infectiousness promotes
natural selection of highly immune evasive variants that have incorporated additional
mutations enabling their resistance to infection-mitigating S variant-cross-reactive Abs and
nonS-specific CTLs. These mutations have been found in proteins responsible for viral entry
(> 30 mutations) and productive viral infection and are driving dominant propagation of
these variants (BA.2.86/ JN.1 clan). - Enhanced intrinsic infectiousness of the BA.2.86 clan triggers Ab-independent VBTIs and
thereby causes PNNAb concentrations to collectively decline, thereby causing highly C-19
vaccinated populations to exert S variant-cross-reactive immune pressure on viral virulence
(i.e., on the specific infection-enhancing site within S-NTD). - Suboptimal S variant-nonspecific immune pressure collectively exerted on viral virulence
likely promotes dominant propagation of an immune evasive, highly infectious immune
escape variant that collectively resists the virulence-mitigating, S variant-cross-reactive
PNNAbs. This could occur through a conformational change in the infection-enhancing site
of SC-2 particles adsorbed on migratory DCs, thereby allowing the new variant to unleash
the PNNAb-mediated blockade on viral trans infection/ virulence.
Why could Omicron not train the CII of non-previously exposed C-19 vaccinees?
- Following its initial VBTI (or 2nd mRNA dose), Omicron was readily
neutralized by high concentrations of mismatched, previously vaccine-
(SIR-)primed Abs that bind with low affinity to S-associated
immunodominant epitopes (thereby triggering SIR). Prevention or
mitigation of infection of susceptible cells following initial VBTI
prevented training of naïve/ unexposed innate immune systems - Subsequent exposure to newly emerged immune escape variants boosts
previously SIR-primed cross-reactive Abs at high titers, thereby ensuring
strong infection-mitigating activity and further preventing triggering and
training of CII
How are the unvaccinated protected from highly infectious variants?
- Their innate immune system is able to quickly lower viral loads and kill
virus-infected cells (via trained, i.e., epigenetically re-programmed,
innate immune cells) without causing a strong recall of previously
infection-primed pNAbs (and, therefore, preventing SIR). - The better the innate immune system is trained, the weaker the recall
effect and the lower the likelihood of PNNAb-dependent BTI. - Unvaccinated individuals who are in good health and avoiding
overcrowding can now successfully rely on their innate immune system
to handle their immune defence entirely
Never immunize during a pandemic!
- Work on prevention:
➢ Avoid overcrowding (especially of vulnerable people),
➢ Foster good health practices
➢ Apply standard hygiene/ sanitation - Let the (asymptomatically/ mildly) infected spread and treat
vulnerable people with antivirals
How will the outcome of the C-19 pandemic be described in future science books?
“Due to suboptimal neutralization of its infectiousness, SC-2 acquired enhanced intrinsic infectiousness. As enhanced intrinsic infectiousness led to suboptimal neutralization of its trans infectiousness in C-19 vaccinees, SC-2 acquired enhanced intrinsic virulence in C-19 vaccinees.”
“Th C-19 mass vaccination program will indisputably be remembered as the largest and most dangerous gain-offunction experiment ever conducted in the history of biology- one which mankind has unleashed to his own species.”
C-19 vaccination does not promote herd immunity!
- mRNA vaccines and vaccine breakthrough infections promoted resistance of new
Omicron sublineages to previously SIR-induced antibodies and therefore expedited
viral infectivity instead of developing herd immunity - Highly C-19 vaccinated populations exert herd immune pressure on viral
infectiousness instead of generating herd immunity against productive infection. - Mass vaccination programs imposed by health authorities and policy makers have
turned highly C-19 vaccinated populations into a breeding ground for immune
escape variants and thereby transformed a natural pandemic into a pandemic of
immune escape variants. Pretending that a pandemic of immune escape variants
generates herd immunity is a contradictio in terminis….. and without herd immunity
a pandemic cannot transition into endemicity…. - Natural infection/ immunization during a natural pandemic prevents immune
escape and thereby generates herd immunity while providing long-lived sterilizing
immune capacity to the individual. In contrast, mass vaccination during a natural
pandemic drives natural immune selection of non-neutralizable and more infectious
immune escape variants and, therefore, fails to generate herd immunity or provide
long-lived sterilizing immunity to the individual.
In the case of a pandemic, natural immunity, including trained innate immunity, is far more efficient (and safe!) than vaccine-induced immunity!
- In the absence of a robust adaptive immune mechanism that protects against
viral virulence, the best alternative to protect against severe C-19 disease during
an immune escape pandemic is to avoid breakthrough infection via trained cellbased innate immunity. - Whereas both cell-based innate immunity and virulence-inhibiting, nonneutralizing antibodies (NNAbs) are S variant-nonspecific, the cell-based innate
immune system (CBIIS) is endowed with adaptive memory whereas deficient T
help will eventually prevent recall of NNAbs. - Due to their thoroughly trained CBIIS, healthy unvaccinated people are
protected from severe C-19 disease and will likely improve their protection when
highly infectious SC-2 variants evolve to exhi it high virulence in ‘untrained’ C-19
vaccinees. - In conclusion: Large-scale natural immunity is required but sufficient to durably
protect an individual from a virus causing ASLVI and to end a natural pandemic.
Why and how is the majority of vaccinees still protected against (severe) C-19 disease?
- The currently observed protection against (severe) disease in C-19
vaccinees fully relies on short-lived NNAbs and strong activation of
CTLs. (Re-)exposure to circulating Omicron descendants or vaccine
booster doses initially extended this protection, but only temporarily
and not without enhancing large-scale immune selection pressure on
viral virulence. - However, once the NNAbs collectively decline below an optimal
threshold, the virus will likely break through their virulence-inhibiting
capacity and unleash a major wave of severe C-19 disease in highly C19 vaccinated populations.
Where has all the science gone?
- Key opinion leaders and health experts are erroneously interpreting
diminished pathogenicity as an indication that the virus is transitioning into
endemicity. They do not understand that reduced pathogenicity of SC-2
does not result from herd immunity but is triggered by broadly infectionmitigating immune response. Repeated activation of broadly infectionmitigating CTLs upon re-exposure to highly infectious circulating variants
results in enhanced immune selection pressure on the virus’ capacity to
prevent NNAb-mediated inhibition of viral virulence. This is now preparing
the virus to lift the immune blockade on severe C-19 disease. - Massive exercises in mutational stamp collection combined with ad hoc
interpretations of epidemiological, biological and clinical data have
prevented scientists from seeing the forest for the trees and are the biggest
obstacle for them to understand the disastrous consequences of this mass
vaccination experiment; their mutational analyses and predictive
epidemiological models merely reflect snapshots and don’t consider the
immunologic dynamics that are driving natural adaptation of the virus. - Although scientists seem to agree that Spike (S)-associated viral mutations are
driven by population-level immune selection pressure, none of them dares to
mention that mass vaccination and subsequent booster immunizations caused
populations to exert large-scale immune pressure on viral infectiousness.
Why does no one investigate the origin of this large-scale immune selection
pressure placed on the virus? - While our experts claim that mRNA vaccination and vaccine breakthrough
infections (VBTIs) protect against severe C-19 disease, they seem to ignore that
both prevent or even abrogate training of the cell-based innate immune system
and promote viral immune escape. - Not understanding that updated vaccine booster doses will only recall
previously primed Abs, thereby expedite immune refocusing and leading to
immune escape, is one of the most blatant examples of immunological
illiteracy. On the other hand, VBTI infections fail to prime new NAbs towards
the infecting circulating variant. - Neither health experts nor scientists seem to understand how enhanced susceptibility to Omicron infection can be reconciled with prevention against (severe) disease in C-19 vaccinees whose antibodies no longer possess sufficient neutralizing capacity.
- No scientist even seems to be considering the risk of this virus evolving
a major – but immunosilent (glycan-based!)- shift transforming it into a
variant that enhances viral virulence in highly vaccinated populations. - Regardless of their astonishing lack of understanding and insight, many
scientists continue to blindly endorse the proposal of incompetent
public health experts and authorities to continue the mass vaccination
experiment with mRNA-based vaccines and to even recommend use of
the latter for fighting other diseases.
Many experts pretended Omicron would end the pandemic. Why have they been wrong?
- Since the advent of Omicron, the pandemic has evolved into a self-catalyzing
chain of large-scale immune escape instead of transitioning into endemicity. - Because Omicron self-catalyzed its evolution into a series of highly infectious
co-circulating descendants, it rapidly caused immune escape dynamics to reach
a point of no return. What this means is that Omicron descendants are now
paving the way to the likely emergence of a naturally selected immune escape
variant with high virulence potential in highly C-19 vaccinated populations - In conclusion: Early Omicron descendants, the infectiousness of which could
no longer be sufficiently neutralized by pre-existing potentially neutralizing Abs,
acquired enhanced infectiousness in vaccinated individuals whereas subsequent
Omicron descendants, the trans infectiousness of which can no longer be
sufficiently inhibited by pre-existing non-neutralizing Abs, will likely acquire
enhanced virulence.
Vaccinated -but not unvaccinated people – in highly C-19 vaccinated populations have turned the natural pandemic into a pandemic of immune escape variants
- Because trained cell-based innate immunity provides strong
sterilizing immunity the unvaccinated did not contribute to
viral immune escape and were not responsible for turning
the natural SARS-CoV-2 pandemic into a pandemic of
immune escape variants. - Each highly C-19 vaccinated population is now planting the
seeds for the emergence of a new Omicron descendant with
high virulence potential (HI-VI-CRON).
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