What Immunology, Virology and Evolution Say About the Future of the Unvaccinated and DISEASE X: Science Worth Doing, Eight Hypotheses Worth Testing

Do the mRNA jabbed truly face a future of eternal boosters, or death? Let's use Science and find out.

There’s a resurgence of concern for the vaccinated in the long run. For example,

Is Dr. Geert Vanden Bossche correct? 'DISEASE X'? Is DISEASE X coming due to the mass vaccination into the teeth (midst) of an ongoing situation of high infectious pressure (circulating virus)

Here I present a balanced view of the basic positions for consideration. Considering both sides of the issues in light of data allows us to state clearly testable hypotheses.

Are mRNA Vaccines Driving Increased Innate Virulence?

The idea that mRNA vaccination has the potential to lead to increased innate virulence of SARS-CoV-2 is primarily centered around several key arguments. Let’s review them.

Immune Escape: Vanden Bossche and others have suggested that the widespread use of mRNA vaccines could encourage the virus to mutate into forms that can evade the immune response elicited by the vaccines. Selective pressure could lead to variants that are not only capable of escaping vaccine-induced immunity but also possess enhanced transmissibility and virulence.

Suboptimal Immune Response: The type of immune response induced by mRNA vaccines is not optimal for preventing transmission of the virus. mRNA vaccines stimulate the production of specific antibodies targeting the spike protein of the virus, at the expense of a broader, more robust immune response that includes innate immunity and cellular immunity (T-cells) that occurs via natural immunity. This could allow the virus to replicate and transmit in vaccinated individuals, possibly leading to the evolution of more virulent strains.

Antibody-Dependent Enhancement (ADE): ADE occurs when non-neutralizing or suboptimal antibodies facilitate virus entry into cells, leading to increased viral replication. If ADE is occurring with SARS-CoV-2, it could contribute to increased disease severity. I have previously reviewed some of the work of Jacques Fantini and colleagues which shows that ADE started with Delta and likely caused the virus to sweep through Europe at a faster pace than would have occurred without vaccination due to interactions between spike Ab, spike protein, and lipid raft proteins.

One aspect of ADE is the enhanced ability of the virus to infect human cells expressing ACE2 receptors. With ADE, more rapid spread of the virus within the host, and potentially increased numbers of types of cells that can be infected, can be expected.

ADE has never been tested in animals other than one macaque monkey study using the original Wuhan-1 variant studied with the original mRNA vaccine.

Impaired Natural Immunity: The immune response to the vaccine might interfere with the body’s natural, non-specific immune defenses against SARS-CoV-2, particularly in the young and healthy, leaving the population more susceptible to future variants.

Evolutionary Pressure Towards Virulence: Evolutionary pressure exerted by mass vaccination campaigns could push SARS-CoV-2 towards increased virulence. This position is based on the hypothesis that viruses under immune pressure from vaccines might not only evolve to escape immune detection but also become more virulent in the process.

Counterpositions: While some viruses may evolve to partially evade immune responses, this does not necessarily correlate with increased virulence. Immune evasion can occur through mechanisms that do not affect, or even reduce, the virus's ability to cause severe disease.

The hypothesis that high virulence might be a disadvantage for a virus because it could lead to higher death rates of their hosts, thus reducing opportunities for transmission, is supported by several lines of reasoning in virology.

While vaccination does exert evolutionary pressure on the virus, this pressure tends to favor mutations that increase transmissibility rather than virulence. High virulence is understood to be a disadvantage for a virus because it may kill the host faster, reducing opportunities for transmission.

Viruses tend to evolve towards a balance of transmissibility and virulence that maximizes their reproductive number (R0), and increased virulence is not always beneficial for the virus's spread.

Under this model, highly aggressive viruses that quickly kill their hosts, like SARS and H5N1 avian flu, encounter problems with spreading because dying hosts cannot transmit the virus effectively. This perspective suggests that virulence might be selected against as a virus spreads in a human population, leading to less lethal versions of the virus that are better adapted to humans.

This idea aligns with the fundamental principle of viral evolution that emphasizes the need for a virus to spread from host to host to maintain the viral population. A virus can only spread if it manages to infect more than one new host, a task complicated if the host dies quickly or if the symptoms are severe enough to isolate the host from others. However, it's noted that in today's highly mobile and densely populated societies, even highly lethal viruses can find efficient transmission routes, particularly during the incubation period when the virus is shed but not yet causing severe symptoms.

Focusing on transmissibility rather than virulence is considered to be more relevant when considering what drives viral evolution. Viruses evolve to be efficiently transmitted to other hosts, and while virulence can accompany transmissibility, it's seen as a secondary effect. This notion challenges the straightforward trade-off model between virulence and transmission, suggesting a more complex relationship where a virus's capacity to spread efficiently does not necessarily mean it will evolve to be more or less virulent per se.

This still leaves us with concerns over immune escape, which can involve the mechanisms we’ve mentioned, including ADE, loss of innate immunity, autoimmunity against immune system proteins, and other targets, which is really immunosuppression, not increased innate virulence. Just like inactivated thimerosal-containing influenza vaccines are known to increase the risk of other non-influenza viral infections (see Cowling), SARS-CoV-2 vaccination via mRNA vaccines may ultimately be seen as immunosuppressive.

Post-Vaccination Induced Polyimmunity and Prophylaxis/Therapies

Evidence suggests that individuals who experience breakthrough infections after vaccination develop a robust immunity that is highly effective against the virus, including its variants. Claims that "hybrid immunity" is more potent than immunity from natural infection or vaccination alone​ are now updated from a recent study that reported that mortality among vaccinated and unvaccinated patients was 70 percent and 37 percent, respectively. In that study, the overall survival rate was two times higher in the unvaccinated group.

Prophylaxis with ivermectin and therapies against spikeopathy (e.g., Nattokinase/Bromelain/Curcurmin, according to Dr. McCullough) to reduce virulence by dissolving spike, are widely available to the vaccinated and unvaccinated.

Ig4 Class Switching in the Vaccinated Concern

Class switching of SARS-CoV-2-specific antibodies to a noninflammatory subtype, IgG4, following vaccination was reported in January 2023. This phenomenon, which does not occur via natural infection alone or in adenovirus-vaccinated persons, appears to occur several months after mRNA vaccination and is influenced by subsequent booster doses or breakthrough infections.

The human immune system can produce different subclasses of IgG antibodies (IgG1, IgG2, IgG3, and IgG4), each with distinct functions. IgG1 and IgG3 are generally considered more proinflammatory, and are efficient at activating complement systems and mediating opsonization, a process where pathogens are marked for destruction by phagocytes. IgG4, on the other hand, is less inflammatory and has a much lower affinity for Fc receptors on immune cells, making it less effective at triggering these immune responses.

The shift towards IgG4 could imply a more tempered immune response to the virus, potentially reducing the risk of vaccine-associated disease complications or other inflammatory complications. However, IgG4 reduces the capacity for mediating complement deposition and antibody-dependent cellular phagocytosis. This should lead to a less reliable mechanism for clearing the virus or infected cells.

Class switching reflects the adaptive immune system's ability to adjust its response over time, possibly as a mechanism to balance effective viral clearance with controlling inflammation. The shift to IgG4 could be interpreted as the immune system's strategy to manage long-term exposure to the antigen, whether through natural infection or vaccination, by favoring a response that minimizes potential tissue damage from inflammation. In this sense, it’s adaptive to the host. However, the inability of individuals to clear viruses can be expected to induce, via pathogenic priming, autoimmunity, and chronic illnesses.

The Ig4 switching findings suggest that the timing and choice of vaccination regimens, including booster doses, may need to consider the potential for such immunological shifts. Understanding how these changes affect long-term protection against SARS-CoV-2, particularly against severe disease, hospitalization, and death, is crucial to generate useful, testable predictions and hypotheses on what will happen to vaccinated individuals in the long run.

Hypothesis 1. Mutation Rate and Virulence Hypothesis

• Background: mRNA vaccination is hypothesized not to increase the virulence of SARS-CoV-2.

• Test: Compare mutation rates and virulence between viruses from highly vaccinated and less vaccinated populations.

• Evidence: Sequencing data and clinical outcomes.

• Interpretation 1 (Falsified): No correlation upholds the that mRNA vaccines do not drive virulence.

• Interpretation 2 (Not Falsified): A correlation between high vaccination rates and increased virulence would suggest mRNA vaccination could be driving the evolution of more virulent strains.

• Limitations: It’s the mutation, not the rate, that determines virulence.

Hypothesis 2. Virulence-Associated Specific Mutations Hypothesis

• Background: mRNA vaccines are theorized not to promote the emergence of SARS-CoV-2 mutations associated with increased virulence.

• Test: Examine the presence of virulence-associated non-synonymous mutations in the SARS-CoV-2 genome from infected individuals in highly vaccinated populations compared to less vaccinated populations.

• Evidence: Genomic sequencing data identifying non-synonymous mutations associated with increased virulence and clinical outcomes of infected individuals and functional assays to test virulence.

• Interpretation 1 (Falsified): The absence of a significant difference in the prevalence of virulence-associated mutations between viruses from highly vaccinated and less vaccinated populations supports the conclusion that mRNA vaccines do not drive the evolution of more virulent SARS-CoV-2 strains.

• Interpretation 2 (Not Falsified): Finding a higher prevalence of experimentally demonstrated virulence-associated non-synonymous mutations in the virus from vaccinated populations suggests that mRNA vaccination may select for mutations that enhance virulence.

• Limitations: The critical factor is the nature of the mutations rather than the mutation rate. Not all mutations lead to increased virulence, and the impact of specific non-synonymous mutations on virulence requires careful evaluation within the context of viral evolution and host-pathogen interaction.

Hypothesis 3. ADE Occurrence Hypothesis

• Background: mRNA vaccines may lead to antibody-dependent enhancement (ADE) in the context of SARS-CoV-2 (Jacques Fantini’s result).

• Test 1: Infect vaccinated ferrets with emerging variants and look for evidence of ADE. Use sequencing to confirm the presence of infection.

• Test 2. Monitor vaccinated individuals for signs of ADE following exposure to new variants and compared to signs in unvaccinated individuals. Use sequencing to confirm the presence of infection.

• Test 3: Perform X-ray crystallography of immune complexes using spike protein from various variants and human cells with ACEs and raft proteins in the presence of different spike antibodies to directly test the modeling by Jacques Fantini et al.

• Evidence: Incidence and severity of breakthrough infections, direct observation of raft protein/ACE2/spike Ab/spike complexes, increased rate of progression and severity of disease in vaccinated vs. unvaccinated ferrets and persons.

• Interpretation 1 (Falsified): Absence of ADE supports rejection of the hypothesis of ADE-related risks.

• Interpretation 2 (Not Falsified): Evidence of ADE in vaccinated individuals would indicate a potential risk associated with mRNA vaccines.

• Limitation: If ADE is incremental, it may be difficult to detect.

Hypothesis 4. Breadth of Immune Response Hypothesis

• Background: Natural infection leads to a broader diversity of Abs than spike-only mRNA vaccines, which cannot possibly induce a broad immune response against SARS-CoV-2.

• Test: Assess and compare the diversity of Abs and clinical outcomes in the immune responses in individuals vaccinated with mRNA vaccines without history of natural infection, same with subsequent infection, the unvaccinated with and without a history of natural infection and vaccinated with vector-based vaccines with history of infection and without history of infection.

• Evidence: Antibody, cellular, and innate immunity markers.

• Interpretation 1 (Falsified): If hybrid immunity does not offer superior protection, this could suggest limitations in the protective breadth of mRNA vaccination.

• Interpretation 2 (Not Falsified): Superior protection via hybrid immunity highlights the benefits of vaccination even after infection.

• Limitation: Focus on Abs alone may be misleading; objective clinical outcomes with sequence-confirmed diagnosis will be required.

Hypothesis 5. IgG4 Class Switch Dynamics Hypothesis

• Background: The dominance of IgG4 following mRNA vaccination may compromise clinical outcomes.

• Test: Track IgG subclass distribution over time in vaccinated and unvaccinated individuals and correlate with booster (vaccinated) and infection outcomes.

• Evidence: Proportions of IgG subclasses and clinical outcomes data post-booster and post-infection.

• Interpretation 1 (Falsified): Conversely, if clinical outcomes are not adversely affected by the predominance of IgG4 antibodies in vaccinated individuals, this would support the hypothesis that IgG4 dominance does not compromise the efficacy of mRNA vaccines in preventing severe disease. This outcome would suggest that despite the class switch to IgG4, the overall immune response remains sufficiently robust to protect against severe outcomes of SARS-CoV-2 infection.

• Interpretation 2 (Not Falsified): Conversely, if data reveal worse clinical outcomes in individuals with a higher proportion of IgG4 antibodies following mRNA vaccination, it would suggest that the IgG4 class switch compromises the vaccine's protective efficacy. This outcome would indicate that the dominance of IgG4 antibodies might be associated with an inadequate immune response to booster vaccinations or natural infections, potentially leading to increased susceptibility or severity of COVID-19.

Hypothesis 6. Evolutionary Pressure Hypothesis

• Background: Vaccination may exert evolutionary pressure favoring increased transmissibility or virulence, or both over increased virulence of SARS-CoV-2.

• Test: Monitor changes in SARS-CoV-2 viral biology in relation to vaccination coverage.

• Evidence: Genetic evolution of the virus, animal and cellular assays. and new infection rate data confirmed by sequencing.

• Interpretation 1 (Falsified): No change in transmissibility, virulence, or both in highly vaccinated populations would rule out each of the three outcome (transmissibility only, virulence only, both, neither).

• Interpretation 2 (Not Falsified): Evolutionary trends toward increased transmissibility, virulence, or both in correlation with vaccination would challenge the strategic use of mRNA vaccines.

Hypothesis 7. Effectiveness of Combined Prophylaxes and Therapies Hypothesis

• Background: Prophylaxis and therapies are effective in both vaccinated and unvaccinated populations against SARS-CoV-2.

• Test: Evaluate the outcomes of prophylactic and therapeutic measures in different populations.

• Evidence: Sequence-confirmed disease incidence, severity, and recovery rates.

• Interpretation 1 (Falsified): Comparable efficacy in treated groups compared to placebo would indicate the futility of these interventions regardless of vaccination status.

• Interpretation 2 (Not Falsified): Higher efficacy in treated groups compared to placebo would inidicate the utility of these interventions regardless of vaccination status.

Hypothesis 8. Long-term Health Outcomes Hypothesis

• Background: mRNA vaccination does not lead to increased rates of autoimmunity or chronic illnesses via pathogenic priming.

• Test: Find autoreactive B-cells; Longitudinally track total health outcomes in vaccinated and unvaccinated individuals.

• Evidence: Incidence of new-onset autoimmunity, polyautoimmunity and chronic illnesses. (See the work done so far here).

• Interpretation 1 (Falsified): No increase in these conditions in mRNA vaccine exposed compared to baseline or compared to unvaccinated rates supports the absence of autoimmune risk from COVID19 mRNA vaccines

• Interpretation 2 (Not Falsified): Increases in autoimmune conditions in mRNA vaccine exposed compared to baseline rates or to unvaccinated supports the absence of autoimmune risk from COVID19 mRNA vaccines.

It goes without saying that the lack of support for earnest, objective studies to address these questions by HHS, or to require them of vaccine manufacturers by FDA over the last three years is unforgiveable.

It also goes without saying that these studies should only be conducted by persons with out massive profit motive from the sales of mRNA jabs.