Vaccines – The Original Antigenic Sin

Vaccines – The Original Antigenic Sin

Abstract
Modern vaccines are widely credited with reducing infectious disease mortality, yet their long-term effects on immune function remain insufficiently examined. At the centre of this debate lies the polarisation of immune memory — particularly the skewing of T helper cell responses toward type 1 (Th1), type 2 (Th2), or type 17 (Th17) pathways. These profiles are not interchangeable, and once established, they define the trajectory of all future responses to that same antigen. This paper explores how aluminium-adjuvanted and mRNA vaccines increasingly imprint Th2/Th17-dominant immunity, in contrast to the durable, Th1-driven responses seen in historical live-virus vaccines like smallpox, and all wild viral infections.

Through a mechanistic analysis of adjuvant signalling, antigen persistence, and cytokine biasing, we show that vaccine-induced outcomes — including tolerance, IgG4 switching, persistent inflammation, and even antibody-dependent enhancement (ADE) — are not anomalies, but expected consequences of immune skewing by vaccine presentation.

The fundamental flaw in modern vaccine design is that it stimulates the wrong branch of the immune system for viral defence. Th2 responses are effective at dealing with extracellular parasites and allergens, but not with viruses that replicate inside human cells. It’s like sending the army to fight a naval war — the army may make some impact on land, but most of the battle takes place at sea. Worse still, the navy is disabled entirely. Your immune system is tricked into deploying the wrong force while the right one stands down. You’re left in a constant battle — but never able to win the war.

As the battle drags on, the immune system becomes exhausted. Its only remaining strategy is to try to coexist with the virus. Surveillance is suspended, and the virus is allowed to travel freely throughout the body, establishing footholds — like viral ghettos — where it can continue to replicate and cause tissue damage. These hidden, unresolved infections often go undetected but drive chronic inflammation and degeneration. Over time, this sets the stage for serious pathology — including cancer.

This is the core failure of vaccine-induced immune skewing: it trains the body to fight infections in the wrong way, and then locks that instruction into memory.

No vaccine using the current design paradigm — including aluminium-adjuvanted or mRNA-based formulations — can produce true antiviral immunity. Worse still, these vaccines retrain the immune system to respond incorrectly in future infections, committing immune memory to the Th2/Th17 profile when a Th1 response is required.

By contrast, the smallpox vaccine succeeded not because it reflects modern vaccine technology, but because it diverged from it. It used a live, replicating virus with no adjuvant, mimicking natural infection and producing robust Th1-driven, sterilising immunity. It should be recognised as the exception that proves the rule — not as a standard that modern vaccines can claim to emulate.

This paper argues that immunological misprogramming through inappropriate vaccine design undermines long-term health and immune resilience. It calls for a complete re-evaluation of vaccine metrics, shifting from short-term antibody titres toward durable, balanced immune education.

Introduction
The immune system is a highly adaptive learning system. It does not simply react; it remembers, categorises, and commits. Once a particular “learning environment” is established during a primary encounter with a pathogen or vaccine, that imprint determines how the body will respond to future exposures. This process, known as immune imprinting or functional polarisation, is deeply influenced by which T helper (Th) pathway is engaged at the start: Th1, Th2, or Th17 (McCarthy et al., 2021; Bancroft et al., 2016; Crotty, 2011).

What many clinicians and the public overlook is that this immune commitment is shaped at the very first point of contact, by the nature of the cells that detect the threat. If antigen-presenting cells like dendritic cells and macrophages dominate the frontline and are activated in a context of intracellular danger, they will release interleukin-12 (IL-12) and type I interferons, pushing naïve T cells toward a Th1 phenotype, ideal for clearing viruses, intracellular bacteria, and promoting cytotoxic immunity. This is the classic antiviral pathway (Seder, Darrah, and Roederer, 2008; Trinchieri, 2003).

By contrast, if basophils, mast cells, or eosinophils are the first to detect the antigen, especially in the absence of strong intracellular danger signals, they release IL-4 and IL-33, skewing the response toward Th2, which promotes antibody production, tissue repair, and, importantly, immune tolerance (Sokol et al., 2008; Perrigoue et al., 2009). Chronic antigen exposure, especially via non-natural routes (e.g., intramuscular injection with aluminium adjuvant), further entrenches these Th2 or Th17 profiles (Marrack, McKee, and Munks, 2009; Reed, Orr, and Fox, 2013). 

This paper examines how different vaccine designs, particularly those using aluminium salts or encoding persistent mRNA antigens, subvert the natural antigen recognition sequence, bypassing mucosal barriers and favouring a non-cytotoxic immune imprint. We contrast this with historical success cases, such as the smallpox vaccine, which elicited a strong Th1 response via live dermal inoculation and viral replication (Fenner et al., 1987; Sanchez-Sampedro et al., 2015).

Understanding how these first cellular responders and their cytokine environments shape long-term memory is crucial for evaluating modern vaccine performance. When we force a Th2 or Th17 response in contexts where Th1 is required, the result will not be full protection but prolonged antigen presence, tolerance, and chronic inflammation (Shi et al., 2009; Katzman et al., 2011; van der Burg et al., 2021). 

Understanding Th1, Th2, and Th17 Pathways
The adaptive immune system relies on T helper (Th) cell polarisation to mount appropriate responses to different classes of pathogens. Upon antigen presentation by dendritic cells, naive CD4⁺ T cells differentiate into one of several effector subsets, predominantly Th1, Th2, or Th17, depending on the cytokine environment, co-stimulatory signals, and the nature of the antigen (Zhu, and Paul, 2008).

• Th1 responses are driven by IL-12 and characterised by IFN-γ production. These responses activate cytotoxic T lymphocytes (CTLs) and macrophages to destroy intracellular pathogens, such as viruses and certain bacteria (Swain, McKinstry, and Strutt 2012; Szabo et al., 2003). Th1 cells also facilitate the development of long-lasting memory with the capacity for sterilising immunity, the complete elimination of a pathogen before it can replicate or cause symptoms (Seder, Darrah, and Roederer, 2008).
• Th2 responses, in contrast, are initiated in the presence of IL-4, leading to production of IL-4, IL-5, and IL-13. These pathways promote B cell class switching, particularly toward IgE and IgG4, and recruit eosinophils and mast cells to combat extracellular parasites. Th2 dominance is also central to allergic responses and can promote tolerance or immune exhaustion when persistently activated (Romagnani, 2000; Paul, and Zhu, 2010; Jeannin et al., 1998).
• Th17 responses, promoted by IL-6, IL-1β, and TGF-β, are involved in recruiting neutrophils and maintaining mucosal immunity. They play a crucial role in controlling fungal infections and extracellular bacteria, but excessive Th17 activity is associated with chronic inflammation and autoimmune disease (Harrington et al., 2005; Ouyang, Kolls, and Zheng 2008; Langrish et al., 2005).

Functional Commitment of Memory T Cells
One of the most critical insights in immunology is that memory T cells are lineage-committed. Once a naive T cell differentiates into a Th1, Th2, or Th17 cell, it retains that functional profile for life (Zhu, Yamane, and Paul, 2010a; Zhu, 2018). This means a memory T cell induced during a Th2-skewed response cannot later generate a cytotoxic Th1-type reaction upon re-exposure to the same antigen (Zhu and Paul, 2010b;).

This principle has profound implications for vaccination. A vaccine that primarily elicits a Th2 response, even if it produces neutralising antibodies, will fail to generate the robust cytotoxic memory needed to eliminate intracellular pathogens effectively. Instead, it may predispose the host to non-sterilising immunity, chronic antigen exposure, and repeated boosting cycles, ultimately reinforcing the same immune skew each time (Pulendran and Ahmed, 2011; Bungener et al., 2008)

This immunological imprinting, often called “original antigenic sin” in viral immunology, becomes especially problematic in the context of respiratory viruses, where Th1 cytotoxicity is required for full viral clearance (Kim et al., 1969; Halstead and O’Rourke, 1977; Reynolds et al., 2022a).

Smallpox and the Myth of Sterilising Immunity

The smallpox vaccine stands alone in the historical record as the only vaccine to confer consistent, long-term sterilising immunity at a population level. Unlike modern subunit or mRNA platforms, the smallpox vaccine used a live, replication-competent virus, vaccinia, which is genetically similar to the variola virus but sufficiently attenuated for use in humans. It did not contain aluminium-based adjuvants, nor did it require repeated boosters. The immune response it triggered was robustly Th1-dominant, involving widespread activation of cytotoxic T cells, NK cells, and high levels of IFN-γ and IL-2 — the classical hallmarks of intracellular pathogen defence (Moss, 2013; Demkowicz et al., 1992).

This vaccine induced strong and lasting memory in both CD4⁺ and CD8⁺ T cell compartments, enabling recipients to clear viral infection before replication could occur — the very definition of sterilising immunityand representing the idea of vaccines that we all believe in. Moreover, the replicating nature of the vaccine virus ensured endogenous antigen presentation via MHC class I pathways, a key requirement for effective cytotoxic T lymphocyte (CTL) priming (Tscharke et al., 2005; Miller et al, 2008). No modern vaccine attempts to replicate this model because of safety concerns and manufacturing limitations.

As a result, the smallpox vaccine is often misleadingly cited as a standard of vaccine efficacy. However, its success lies not in its representativeness, but in its exceptional divergence from modern vaccine design. Unlike today’s aluminium-adjuvanted or mRNA-based products, which bypass intracellular processing and focus on antibody production, the smallpox vaccine closely mimicked natural infection. Its use of a live virus without a strong Th2-skewing adjuvant enabled a balanced and robust Th1-mediated immune response, which no modern interventions can replicate (Simon et al., 2014; Kim et al., 2006; Sasaki et al., 2003).

Sterilising immunity — where the immune system prevents infection entirely — is the gold standard in vaccination and should be the only model pursued. Historically, this level of protection has only been reliably achieved using live-attenuated vaccines that closely mimic the behaviour and tissue tropism of the wild virus, enabling the immune system to mount a comprehensive and correctly balanced response (Slifka and Amanna, 2014; Plotkin, 2010). In contrast, inactivated or subunit vaccines fail to achieve sterilising immunity and require adjuvants to boost effectiveness (Cohet et al., 2019). However, adjuvants can distort the natural immune response, resulting in skewed immunity that fails to resolve infection and may promote long-term immune dysregulation (Pulendran and Ahmed, 2011; Reed, Orr, and Fox, 2013). Preserving the integrity of immune system architecture should take precedence over short-term antibody titres, particularly when long-term safety data are lacking (Liu et al., 2005).

Vaccine Pressure and Viral Mutation
Modern vaccines, by contrast, are designed to induce non-sterilising immunity, leaving individuals vulnerable to asymptomatic infection and transmission. The resulting immune memory is Th2-biased — a profile increasingly associated with chronic inflammation, immune tolerance dysfunction, and autoimmunity, especially with early-life or repeated exposures (Brewer et al., 1999; HogenEsch 2002; Lindblad 2004; Aimanianda et al., 2021; Berin and Screffler, 2008; Marrack, McKee, and Munks, 2009).

This partial immune pressure creates ideal conditions for viral evolution. When viruses are exposed to sub-neutralising antibody levels or poorly cytotoxic immune environments, they are pressured to mutate in ways that enhance their ability to evade immunity and persist — a phenomenon known as vaccine pressure (Muñoz-Alía et al., 2017; Geoghegan, and Holmes, 2018).

For example, the measles virus historically maintained an exceptionally stable genome (Langmuir et al, 1962), but after widespread vaccination, mutations began to accumulate in response to immune selection (Hadfield n.d.). Moore (2021) notes that “escape mutations” typically arise under selective pressure from antibodies that restrict but do not eliminate viral replication. Wang et al. (2021) demonstrated that vaccine-resistant mutations such as Y449S in SARS-CoV-2 emerged in direct correlation with rising vaccination rates in Europe and the US, disrupting neutralising antibodies while reducing infectivity, a form of immune evasion rather than viral enhancement (Wang et al., 2021).

Pouwels et al. (2021) further highlighted that waning vaccine-induced immunity, in combination with viral evolution, threatens long-term vaccine efficacy. This underscores the broader immunological risk: when vaccines train the immune system to tolerate rather than eliminate, we don't just fail to prevent disease, we cultivate its adaptation (Pouwels et al., 2021).

The use of non-sterilising vaccines should be avoided at all costs because they drive the target virus to mutate, to become more virulent (Read et al., 2015; Boots, 2015; Miller and Metcalf, 2019;  Garcia-Beltran et al., 2021).

Th2-Skewed Immune Memory in Modern Vaccination

Modern vaccine formulations, particularly those using aluminium salts (commonly referred to as “alum”), are designed to elicit strong antibody responses. Alum has been used for nearly a century and remains the most widely used adjuvant in licensed human vaccines. Its mechanism of action is to stimulate the Th2 arm of the adaptive immune system, encouraging B cell differentiation and class switching to immunoglobulin subtypes such as IgG4 and IgE, rather than Th1-associated IgG1 or IgG3 cytotoxic T cell responses (Brewer et al., 1999; Marrack et al., 2009). Notably, this Th2-biased response occurs independently of the classical cytokine drivers IL-4 and IL-13 (Brewer et al., 1999).

While this response is sufficient to provide partial protection against many pathogens, it does not replicate the full immune architecture induced by natural infection or live-attenuated vaccines with no adjuvant. Importantly, Th2-biased immune memory is self-reinforcing: once initial priming is skewed toward Th2, subsequent exposures to the same antigen, whether through booster shots or natural infection, will continue to activate the same pathway (Bancroft et al., 2016; Bielinska et al., 2016; Kidd, 2003). As a result, this immune imprinting establishes a long-term bias, causing the host to respond to related pathogens with a Th2-skewed profile, even when later exposed to signals that would normally promote a Th1 response (Cao et al., 2021).

The preference for Th2 stimulation over Th1 is not benign. Th2-dominant responses are associated with humoral tolerance, chronic inflammation, and the inhibition of cell-mediated immunity, which is essential for clearing intracellular pathogens such as viruses (Bungener et al., 2008). Furthermore, in susceptible individuals, repetitive Th2 stimulation contributes to the development of immune pathologies, including IgE-mediated allergies, eosinophilic disorders, and IgG4-related disease (Finkelman et al., 1988; Umehara et al., 2012a). Immune cells also shift function in response to their chemical environment; for example, mast cells, typically known for their pro-inflammatory roles, can adopt anti-inflammatory and immunosuppressive behaviour in the presence of IgE (Galli, Grimbaldeston, and Tsai 2008).

It is highly improbable that repeated administration of aluminium-adjuvanted vaccines, particularly when started in infancy, would not contribute to a persistent Th2 bias in recipients, and regulatory IgG4 class switching in a portion of that population. It is the natural conclusion of events. Although manifestations may remain subclinical in many recipients, the underlying shift in immune architecture can silently increase vulnerability to immune evasion, chronic disease, and antibody-dependent enhancement (ADE) upon exposure to related pathogens later in life (Guimaraes et al., 2015; Bortolatto et al., 2015; Pillai 2023).

mRNA Vaccines and the Inescapable Shift Toward Th2 Immunity
Despite initial claims that mRNA vaccines elicit a Th1-skewed response, the documented induction of IgG4 class switching and even IgG4-related disease after repeated exposure demonstrates a definitive shift away from Th1 immunity. IgG4 cannot emerge from a sustained Th1-dominant environment; its production requires cytokine signals characteristic of Th2 and regulatory responses, including IL-4, IL-10, and TGF-β (Finkelman et al., 2005; Umehara et al., 2012a). This shift is not theoretical — it is evidenced by peer-reviewed studies documenting elevated IgG4 following mRNA vaccination (Irrgang et al., 2023; Gelderloos et al., 2024), as well as case reports of vaccine-induced IgG4-RD (Aochi, Uehara, and Yamamoto, 2023; Zhang et al, 2024). There is no known immunological pathway in which a persistent Th1 environment produces IgG4. Therefore, the presence of IgG4 alone is sufficient to prove that these vaccines have switched to a Th2-dominant profile. While population-level studies are still emerging, the well-established immunological pathways leading to IgG4 dominance and tolerance make this outcome a biologically predictable consequence of repeated mRNA vaccination (Valk et al., 2024; Irrgang et al., 2023).

IgG4 Class Switching and Immune Tolerance

When the immune system encounters persistent antigen exposure, whether through chronic infection, environmental allergens, or vaccination, it may adapt by dampening inflammatory responses to prevent tissue damage. One hallmark of this adaptive response is class switching to IgG4, a unique antibody subclass associated with immune tolerance, non-cytolytic behaviour, and suppressed effector functions. Unlike IgG1 or IgG3, IgG4 does not efficiently fix complement or trigger antibody-dependent cellular cytotoxicity (ADCC) (Oskam et al., 2023; Rispens and Huijbers, 2023; Crescioli et al., 2016).

Under conditions of repeated antigen exposure, IgG4 levels gradually rise as a tolerance mechanism. This phenomenon is well-established in allergen immunotherapy, where controlled exposure to allergens shifts the antibody profile from IgE to IgG4, signifying the induction of immune tolerance (Uversky et al., 2023; James et al., 2011).

A similar pattern is now being observed in recipients of repeated COVID-19 mRNA vaccines. Multiple studies confirm that successive dosing, particularly at short intervals with persistent spike protein expression, promotes IgG4 class switching (Irrgang et al., 2023; Buhre et al., 2023; Lasrado et al., 2024; Espino et al., 2024). Although initially interpreted as regulatory or non-inflammatory, the growing dominance of IgG4 signals a deeper concern: the immune system has become tolerant to a pathogenic antigen, the spike protein, when the goal should be robust clearance, not coexistence (Uversky et al., 2023; Martin Perez et al, 2025).

Importantly, this IgG4 bias is not unique to mRNA platforms. Chronic antigen exposure in a Th2- or Treg-skewed immune environment, such as that induced by aluminium-adjuvanted vaccines, can also drive IgG4 production (Brewer et al, 1999; Umehara et al., 2012b). It is therefore implausible that aluminium-based vaccines do not contribute to similar skewing, even if more gradually or sub-clinically.

While IgG4 is frequently described as “anti-inflammatory,” this comes at a cost. In contexts where antigen elimination is critical, such as viral infections or cancer, an IgG4-dominated response impairs immune efficacy and facilitates persistence or immune escape (Wang et al., 2020; Karagiannis etal., 2013; Topchyan, Lin, and Cui, 2023). The pathological potential of this regulatory antibody is exemplified in IgG4-related disease (IgG4-RD), a systemic fibroinflammatory condition that arises when this otherwise tolerogenic mechanism becomes dysregulated (Stone, Zen, and Deshpande, 2012; Aochi et al., 2023; Ohyama, 2013).

Immune Skewing and Chronic Disease

Persistent bias toward Th2 and regulatory T cell (Treg) responses gradually erodes the body’s capacity to mount effective cytotoxic and inflammatory reactions when necessary. This is especially concerning for cancer surveillance, viral clearance, and control of intracellular pathogens — all of which require strong Th1-type immunity. Vaccines that repeatedly stimulate Th2 or Treg pathways shift immune resources toward antibody production at the expense of cellular immunity, leaving the host vulnerable to chronic infection and immune escape (Rook, 2009; Brewer et al, 1999; Marrack, McKee, and Munks, 2009).

This is particularly troubling in the context of modern vaccination schedules, where infants and young children encounter dozens of antigens and adjuvants during critical windows of immune development. The early-life immune system is highly impressionable, and repeated activation of Th2 pathways fosters long-term immunological imprinting. This skewing contributes to the rising prevalence of allergic diseases, asthma, atopic dermatitis, and autoimmune conditions — all linked to dysregulated Th2 and Treg activity (Meng et al., 2016; Lyons-Weiler, 2020; de Planell-Saguer, Lovinsky-Desir, and Miller 2014; Sun et al., 2016).

When effector responses are persistently suppressed in favour of regulation, the result is a state of “immune exhaustion” or “immune paralysis.” This has been observed in chronic infections and persistent antigen exposure, and is now emerging in repeated mRNA vaccine recipients, where signs of a dysfunctional immune profile are being documented (Irrgang et al., 2023; Utzschneider et al., 2016; Buhre et al., 2023; McKinney and Smith, 2016; Benitez Fuentes et al., 2022).

Ultimately, skewing immune responses away from Th1 pathways undermines the body's ability to defend against real threats. This imbalance contributes to the growing epidemic of chronic disease in industrialised societies. The very tools intended to prime the immune system are, by design, disrupting it. This is reflected in increased healthcare visits and adverse outcomes following vaccination, as shown in several large observational studies (Aaby et al., 2018; Lyons-Weiler, 2020; Simpson et al., 2002; McFadden et al., 2015; Chen, Zhang, and Deng 2012).

The Role of IgA in Immune Skewing: From Mucosal Defence to Tolerance

Immunoglobulin A (IgA) is essential for mucosal immunity, particularly in the respiratory and gastrointestinal tracts. Secretory IgA (sIgA) neutralises pathogens and blocks epithelial adherence without provoking inflammation (Macpherson et al., 2008).

However, during chronic antigen exposure, such as repeated vaccination or persistent spike protein expression, IgA responses become dysregulated. This is mediated by the Th17–Treg axis, particularly in mucosal tissues (Cerutti et al., 2011; Cao et al., 2012; Traxinger et al., 2022).

Initially, Th17 cells, stimulated by IL-6 and TGF-β, promote mucosal defence and class switching to IgA (Ivanov et al., 2009; Hirota et al., 2013). But chronic stimulation shifts the balance toward Treg dominance (Akdis and Akdis 2014). Regulatory T cells release IL-10 and TGF-β, driving further IgA (especially IgA2) and IgG4 production (Cerutti et al., 2013; Izcue, Coombes, and Powrie, 2006; Taylor et al., 2006).

In this tolerogenic state, IgA is no longer protective. It coats pathogens in a way that blocks their detection by effector cells, a process known as “antigen blocking” (Wegman et al., 2021). This allows ongoing colonisation or viral shedding while masking true infection (Mantis, Rol, and Corthesy 2011).

This dysfunctional IgA response, coupled with IgG4 class switching, marks a suppressive immune state induced by vaccine-driven chronic antigen exposure. Rather than preventing infection, this form of “tolerance” facilitates pathogen persistence under the false appearance of immunity (Stacy et al., 2021)

Original Antigenic Sin and the Consequences of Th Skewing

Original Antigenic Sin (OAS) was first noted in influenza research: the immune system preferentially recalls memory responses from its first encounter with a virus, even against mutated strains (Francis, 1960). Traditionally considered in terms of epitope recognition, recent studies show that OAS also includes imprinting of the immune environment, particularly the dominant T-helper (Th) profile (Zang et al., 2019; Reynolds et al., 2022b).

When first exposure to a pathogen like SARS-CoV-2 occurs via intramuscular vaccination, the immune system is trained to mount a Th2-skewed response. This results in memory B cells biased toward IgG4 or IgE production, instead of Th1-driven cytotoxic activity more appropriate for viral defence (Tang et al., 2022; Irrgang et al., 2023; Espino et al., 2024).

Upon real viral exposure, the immune system recalls this biased profile, even if it is maladaptive. As a result, the host may:

• Fail to mount a robust cytotoxic T-cell response.
• Overproduce non-neutralising antibodies that form immune complexes without clearing the virus.
• In some cases, trigger antibody-dependent enhancement (ADE) or allow persistent asymptomatic infection and viral shedding.

This broader understanding of OAS suggests that immunological imprinting is not just about antigen targeting; it’s about the kind of immune response that becomes “hardwired.” While antigenic drift involves pathogen evolution, Th-skewed imprinting distorts host defence, potentially long-term and across related viruses (Park et al., 2022; Zang et al., 2019; Pusnik et al., 2024)

Antibody-Dependent Enhancement and COVID-19 Vaccination

Antibody-dependent enhancement (ADE) occurs when antibodies, instead of neutralising a pathogen, facilitate its entry into immune cells such as monocytes and macrophages, triggering hyperinflammation and worsening disease outcomes. This is not a rare anomaly. ADE is a well-documented risk whenever the immune system is primed incorrectly, particularly when Th2 and Th17 pathways dominate the response to viral infections. This skew is commonly induced by injected vaccines that bypass the mucosal immune system and employ adjuvants to boost antibody production (Ricke and Malone, 2020; Xu et al., 2021; Han et al., 2011; Shukla et al., 2020). Vaccine-induced Th17 cells retain their memory for years, and this polarisation can lead to suboptimal immune responses upon subsequent exposures, particularly when a cytotoxic Th1 response would be more appropriate (Lindenstrøm et al., 2012).

A Th2-dominant profile generates antibody-mediated immunity at the expense of the cytotoxic responses required to clear intracellular pathogens. IgG4 and IgE antibodies are characteristic of this skewed profile and are associated with poor viral clearance, allergic-type inflammation, and immune tolerance (Marchese et al., 2024; Portilho et al., 2024). Th2 activation drives the recruitment of eosinophils, mast cells, and basophils, which release IL-4, IL-5, and IL-13, cytokines that directly suppress Th1 and CD8+ cytotoxic T-cell activity (Guenova et al., 2013; van de Burg et al., 2023). This creates a permissive environment for viral replication while escalating inflammatory damage, the hallmark of ADE. 

This mechanism is well-established in flaviviruses. Prior infection or vaccination against Dengue virus can enhance the severity of subsequent Zika virus exposure through heterologous ADE (Dejnirattisai et al., 2016).

Even live-virus vaccines, such as the measles-mumps-rubella (MMR) vaccine, tilt the immune response toward Th2, not because of aluminium (which they do not contain), but because they bypass the mucosal immune system and fail to fully replicate the tissue-tropic signalling of wild virus infection. Post-vaccination studies have shown elevated IgE levels, a signature of Th2 dominance (Imani and Kehoe, 2001). This recruits cells poorly suited for viral clearance while suppressing interferon-gamma and cytotoxic lymphocyte activity. Despite using replication-competent measles virus, these vaccines fail to recreate the sterilising immunity induced by natural infection. Instead, they produce “modified measles” — a milder clinical picture in vaccinated individuals who nonetheless carry and transmit the virus (Rosen et al., 2014; Damien et al., 1998). As a result, silent spread among the vaccinated has become the new norm. Measles outbreaks are now disproportionately reported in vaccinated populations (Avramovich et al., 2018; Poland, and Jacobson, 1994).

COVID-19 vaccination presents a more extreme case. The persistent antigen signal from mRNA vaccination, particularly with repeated dosing, drives class-switching toward IgG4 and entrenches a Th2-skewed profile (Lasrado et al., 2024; Perez et al., 2025). This suppresses cytotoxic lymphocytes and promotes immune tolerance, allowing for persistent viral reactivation, immune complex formation, and multi-system inflammation (Uversky et al., 2023). In this context, the vaccine not only fails to prevent disease but becomes a contributing factor to its chronicity and recurrence. The immune pathology observed after multiple mRNA doses, including organ damage, reactivation of latent viruses, and immune exhaustion, is a direct result of this maladaptive Th2/IgG4 imprinting (Erice et al., 2025; Marchese et al., 2024).

COVID-19 thus offers a clear proof-of-principle: when the wrong arm of the immune system is activated against a virus, the result is not protection, but enhanced disease (Hou, Kang and Kim, 2009; Uversky et al., 2023; Irrgang et al., 2022; Valk et al., 2024; Gelderloos et al., 2024). Additionally, repeated COVID-19 vaccination has been shown to trigger the reactivation of latent viral infections, compounding the individual’s total disease burden (Chen et al., 2023; Gringeri et al., 2022; Hertel et al., 2022). 

Early warning signals regarding COVID-19 vaccine safety were evident within the first month of rollout (Gee et al., 2021), yet recognition of these concerns remained limited within the broader scientific community, a resistance noted by Lancaster (2024).

Discussion: The High Cost of Immune Misprogramming

The immune system is not a passive barrier; it is a dynamic, memory-driven network that learns, adapts, and responds based on its earliest instructions. The nature of these early encounters — whether through natural infection or vaccination — defines not just immediate protection, but the shape of all future responses. This is the essence of immune imprinting.

Understanding the distinct functions of the Th1, Th2, and Th17 pathways is critical to evaluating vaccine performance. Th1 responses generate cytotoxic memory capable of clearing intracellular pathogens, while Th2 and Th17 pathways promote antibody production, tissue repair, and mucosal defence. These pathways are mutually antagonistic: when one is activated, the others are suppressed. Once a naïve T cell commits to a lineage, it remains fixed — memory T cells cannot be reprogrammed later. This principle has profound implications for vaccination, as the type of response a vaccine elicits determines whether the body will resolve or tolerate a future infection.

The smallpox vaccine stands as a historical outlier, not a model of modern practice. It induced true sterilising immunity via a live, replication-competent virus, engaging the Th1 pathway and producing long-lasting cytotoxic memory. In contrast, today’s subunit, inactivated, and mRNA vaccines bypass mucosal immunity and intracellular replication. They rely on adjuvants or synthetic constructs that preferentially stimulate Th2 or Th17 responses — insufficient for complete viral clearance.

This immunological misalignment carries significant evolutionary consequences. Vaccines that induce partial, non-sterilising immunity apply selective pressure on viruses, encouraging mutations that evade immune detection. As demonstrated with SARS-CoV-2, vaccine-resistant mutations like Y449S have emerged in direct correlation with rising vaccination rates. This is not random drift but a predictable outcome of immune selection in a suboptimal response environment.

Aluminium-based adjuvants, used for nearly a century, are well-documented to drive Th2-dominant responses, even in the absence of IL-4 or IL-13. Repeated exposure reinforces this skewing and promotes class switching to IgG4 and IgE. This immune profile may offer transient protection but fails to recreate the coordinated, cytotoxic, and sterilising immunity induced by live-virus exposure. Over time, this imprinting becomes fixed, guiding all future responses along the same non-cytotoxic track.

mRNA vaccines exacerbate this issue. Despite early claims of a Th1 bias, repeated dosing has been shown to induce IgG4 class switching — a hallmark of Th2 and regulatory (Treg) environments. IgG4 cannot emerge from Th1 conditions. Its presence alone confirms a shift away from cytotoxic immunity. This shift, once initiated, is not reversible, even with subsequent Th1-oriented vaccination attempts.

IgG4 is not a neutral antibody. While often described as "anti-inflammatory," it promotes immune tolerance, impairs pathogen clearance, and facilitates persistence in contexts where resolution is required. In cases like COVID-19, where the spike protein persists through repeated mRNA exposure, this tolerance enables chronic infection, immune exhaustion, and potentially, the reactivation of latent viruses.

Beyond IgG4, chronic vaccine-driven antigen exposure also distorts mucosal immunity. The role of IgA, normally protective in mucosal surfaces, becomes suppressive when overproduced in a tolerogenic environment. Instead of neutralising pathogens, dysregulated IgA may mask them from immune detection — facilitating colonisation and spread under the illusion of protection.

All of this culminates in the phenomenon known as “original antigenic sin.” This concept, once limited to B-cell epitope recognition, now extends to the very type of immune response imprinted. When a viral vaccine teaches the immune system to respond with tolerance instead of clearance — to suppress instead of eliminate — that instruction becomes embedded. Even when the pathogen mutates, the immune system recalls the first response, not the one it needs.

This skewing does not only hinder viral clearance; it predisposes to a wide spectrum of chronic diseases. Persistent Th2 and Treg bias undermine cancer surveillance, promote allergic and autoimmune disorders, and contribute to the immune exhaustion increasingly documented in recipients of repeated vaccination. These outcomes are not coincidental — they are consistent with the immunological architecture imposed by modern vaccine design.

Antibody-dependent enhancement (ADE) is a final, severe manifestation of this misdirection. When non-neutralising antibodies facilitate viral entry into immune cells, the result is not immunity but intensified disease. This risk is amplified in a Th2/IgG4-dominant landscape, where cytotoxic responses are suppressed and viral clearance is impaired. The COVID-19 vaccination campaigns have demonstrated, at population scale, the dangers of programming the wrong immune pathway — reinforcing tolerance in a context that demands cytotoxic defence.

The immune system of a healthy human is a finely tuned, self-correcting mechanism that has evolved to learn from exposure, resolve infections, and adapt with minimal disruption to the host. This system is not designed to be micromanaged. As such, any external intervention — including vaccination — must operate within the framework of immune logic, not against it.

Current vaccine strategies often violate this principle. By promoting Th2-biased responses through adjuvants like aluminium or persistent mRNA exposure, they override the immune system’s natural preference for Th1-driven viral clearance. This artificial skewing can create a form of “immune paralysis” where tolerance, not resolution, becomes the default.

Vaccination is frequently framed as a public health imperative, but it must also meet the standard of first, do no harm. When early-life vaccination repeatedly activates Th2 pathways, the resulting immune imprint becomes permanent — shaping how that individual responds to pathogens for life. The rise in chronic immune disorders, allergies, and immune exhaustion observed in vaccinated populations should be interpreted in this light: not as random outcomes, but as consequences of long-term immune misdirection.

What is most troubling is not that this risk was unknown, but that it has been ignored. The literature has long documented the mutual exclusivity of Th1 and Th2 pathways, the permanence of immune memory imprinting, and the suppressive role of IgG4. Yet regulatory agencies and public health bodies continue to promote vaccine strategies that reinforce these patterns. If health professionals within national systems like the NHS understand these dynamics — and it is almost certain many do — then the silence must be attributed to systemic suppression, not scientific ignorance.

This calls for a profound realignment of priorities. Vaccine policy must be led by immunological outcomes, not pharmaceutical convenience or political narrative. Sterilising immunity — the gold standard — has been largely abandoned in favour of tolerising strategies that prioritise antibody levels over actual resolution. This has consequences not only for individual health but for population-level pathogen evolution.

We must now confront an uncomfortable truth: vaccines have the power not only to protect, but to miseducate. When the immune system is repeatedly trained to tolerate instead of resolve, we create the illusion of immunity while silently suppressing our true defences. The consequences are cumulative, persistent, and, in some cases, irreversible.

The failure to acknowledge immune misprogramming is not just a scientific oversight — it is a breach of ethical responsibility. It is time to re-evaluate not only the composition of vaccines but the structures of oversight that determine how such products are approved and deployed. Health, not ideology, must be our guiding principle.

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