molecular mimicry hpv vaccine Archives

Molecular Mimicry and Autoimmune Disease

Published on September 22, 2016

5177 views

Over the last several years the debate over whether the molecular mimicry observed in vaccines, viruses and other pathogens can evoke autoimmune disease has garnered considerable interest. The argument behind molecular mimicry is that if foreign pathogens like bacteria, viruses and vaccines are similar enough in structure or function to our innate, ‘self’ peptide sequences, they can evoke an autoimmune response in the exposed individual. This suggests that a molecular mimic contained in a pathogen is the Trojan horse that tricks the body into activating or over-activating an immune response. Recent reports suggest some evidence that this may be true. Other research suggests that the entire notion is fundamentally flawed. On which side one falls, rests upon how one understands immunity. Is the immune system an army that identifies self from non-self invaders and fends off the foreigners or is it a more finely tuned system that only activates when danger or damage is present?

Those in self-nonself camp, the more dominant of the two camps, would see a threat in the molecular mimics and link those to autoimmunity. Whereas the danger or damage theory proponents would argue that the presence or absence of molecular mimicry by itself means nothing unless the mimicked code evokes damage. Data can be found supporting either argument. For me, however, the danger/damage theory offers more potential utility in both diagnostic and therapeutic options going forward.

What is Molecular Mimicry?

Self versus Nonself. From the perspective of a self versus non-self proponent, when external pathogens contain protein motifs (code patterns) that mimic those of our internal and innate proteins, the immune system recognizes the foreign invader and attacks not only the dangerous pathogen, but the innate molecules that contain those same protein motifs too, evoking all sorts of damage to potentially many different tissues and organs. This occurs when there is structural similarity between the pathogen and immune cells as well. The pathogen slips in, binds to a receptor and initiates the inflammatory immune response. In either case, the immune response to the environmental pathogen results in a disease process identified as autoimmune – the immune system attacking itself.

Danger or Damage Theory. To the damage theory proponents, the molecular mimicry would mean nothing in and of itself, but becomes important when the mimicked code initiates deleterious activity. The immune system activity or hyperactivity identified as ‘autoimmune‘ by the self/nonself folks, would be indicative of a continued disease process and a failing immune system by the damage theory proponents.

The Case for Molecular Mimicry and Autoimmunity

The H1N1 flu vaccine Pandemrix triggered an outbreak of narcolepsy in Scandinavian children. Researchers found that proteins within Pandemrix vaccine mimicked both sequence code and structural similarities of innate proteins that then initiated immune system attacks on the hypocretin/orexin neurons. The hypocretin/orexin neurons are responsible for regulating wakefulness and known to be attacked and diminished in patients with narcolepsy. Molecular mimics within Pandemrix were shown to have triggered an immune system attack on those neurons.

Similarly, molecular mimicry has been suspected in the autoimmune diseases that emerge post Gardasil or Cervarix, the HPV vaccines. With the HPV vaccines, researchers have identified 82 pentamer (5) level mimics and 34 heptamer (7) level mimics in the HPV 16L component. The offending motifs control a variety of cell behaviors related to cardiac functioning, cell permeability and cell death. This finding led the researcher to postulate that the mimicked motifs controlling cardiac functioning could be culprits in the post HPV vaccine incidences of sudden death.

Molecular mimicry is also believed to be involved in the onset of Type 1 Diabetes, Lupus, Multiple Sclerosis and other diseases, including some neurological disease processes.

The Case Against Molecular Mimicry and Autoimmunity

In the field of proteomics researchers have identified massive overlap between the protein code embedded in viral and bacterial pathogens and vaccines and the ‘self’ suggesting that no human protein, not even one, is exempt from molecular mimicry. Indeed, in the most recent study of bacterial peptide motifs, researchers found that out of 36,104 bacterial proteins investigated, only 104 hepta (7) sequence proteins did not match. Mathematically, this is astounding because those 36,104 heptapeptides would produce 1,280,000,000 heptapeptide variants. Similar research investigating viral molecular mimics found considerable overlap in the protein codes between the human T-lymphotropic virus 1, Rubella virus, and hepatitis C virus, in the HPV virus, and of course, the most recent research identifying molecular mimicry associated with the flu vaccine and proteins that regulate wakefulness. If these molecular mimics are so common, how then do we explain the activation of ‘autoimmune’ disease in some individuals but not others?

Two Models of Immunity: Self versus NonSelf and the Danger or Damage Theory

Is immunity the battle between self or host immune armies whereby molecular mimicry represents the Trojan horse of the other, the foreign invader, tricking the host into attacking itself – autoimmune disease? Within this context, molecular mimicry is the threat. In contrast, if immunity is the successful battle between host functioning and host ill-functioning, then a threat exists only to the extent it can initiate damage. Here neither the foreignness, the non-self aspects of the threat, nor the Trojan horses of molecular mimics matter unless they exert damage.

With the flu vaccine, researchers showed that the molecular code embedded in the Pandemrix vaccine activated an immune response against the hypocretin/orexin neurons inducing narcolepsy, but only in those individuals that had a genetic mutation associated with narcolepsy. Whether the rash of post vaccine narcolepsy cases observed in general population was also triggered by unmasking latent genetic or environmental predispositions attacking those same neurons, remains unclear and has not been investigated.

What is clear is that the function of the mimicked code was to turn on a sequence of events that damaged the host’s wake/sleep neurons. The fact that the code was foreign did not make a difference, the fact that there were additional identical patterns of code in the vaccine may or may not have made a difference (the research is unclear), what was important was the function of these mimicked protein codes. In this case, those codes attacked the hypocretin/orexin neurons causing damage. Some individuals were able to fend off this attack and suffered no apparent damage while others were not and therein lies the problem.

If we assume, as the research is now suggesting, that molecular mimics are pervasive across all environmental pathogens, then we can no longer take this simplistic self versus nonself view of immune reactivity. Moreover, we can no longer ignore the functions of the viral protein motifs contained within any given vaccine (or bactericidal agent). We must begin to look at the damage these motifs might do, especially when magnified with adjuvants and administered into a population with active and latent disease. Only then can we truly assess the risks that vaccines and other medications confer to some individuals.

Final Thoughts: Beyond Self versus NonSelf

It is likely that the molecular mimics, the snippets of self-same code and structural similarities between viral and bacterial pathogens and the humans/animals that they attack were always already there as a product of evolution. The proteins and other compounds in the vaccines that were meant to protect against pathogens, may only serve to introduce them to the host and trigger reactions in so disposed individuals. Further, the damage these mimics evoke is not some error in immune system function, but precisely the opposite. That is, the immune system is not attacking itself as presupposed by autoimmune theory, but is doing what it’s supposed to do – fighting off pathogens and cleaning up the remains of the battle, a possibility more akin to the danger or damage framework of immunity.

Perhaps, the illnesses we identify as autoimmune are evidence of a pathogen’s successful attack on the organism and the host’s inability to repel it. Think bacterial resistance to antibiotics; the pathogen adapted, the host did not and the pathogen wins. If we consider molecular mimicry exists, and that the ensuing disease process are the targets of pathogenic proteins rather than a by-product of an over exuberant immune system, then it begs the question, why some individuals can successfully fend off the attack while others cannot. The answer may lie somewhere between the combination of vaccine proteomics, individual genetics and environmental exposures; something far more complicated than the simple antibody response measure of immunity.

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter.

Image created using Canva AI.

This post was published previously on Hormones Matter in March 2014.

The Flu Vaccine, Molecular Mimicry, Narcolepsy: Clues to Gardasil Injury

by Chandler Marrs, PhD

Published on November 18, 2015

7578 views

What do molecular mimicry, the H1N1 Flu vaccine and the HPV vaccines Gardasil or Cervarix have to do with the brain neurons involved in narcolepsy or hypersomnia? Plenty. Researchers are learning that vaccine induced immune reactions can destroy innate cells via molecular mimicry and in the case of the flu vaccine, the hypocretin/orexin neurons responsible for maintaining wakefulness are attacked. Idiopathic hypersomnia, a derivative of narcolepsy is one of the many side effects reported by post Gardasil girls and women. Could the HPV vaccine be attacking those same neurons? Is molecular mimicry at play in the HPV vaccine too? The answers are yes and possibly, but with the HPV vaccine, the molecular mimicry is more widespread and the research only beginning to delineate its effects.

What is Molecular Mimicry?

Molecular mimicry is the notion that foreign pathogens like bacteria, viruses and vaccines can be so similar in structure or function to innate, ‘self’ peptide sequences that they evoke an autoimmune response in the exposed individual. Molecular mimics are thought to be involved in the onset of Type 1 Diabetes, Lupus, Multiple Sclerosis and other diseases, including some neurological disease processes.

Molecular mimics are snippets of protein code embedded within the pathogen that are either functionally similar and contain sequences of identical code to those found innately in humans, or structurally similar and because of their shape can bind to and activate an immune cell receptor. The protein codes, called motifs, are instructions that govern all aspects of the cell’s activity levels, and indeed, our very health and survival. Some codes tell the cell to live and how to function, others tell the cell to die and even how to die. The thought is that when external pathogens contain protein motifs that mimic internal and innate protein motifs, our immune system recognizes the foreign invader and attacks not only the dangerous pathogen, but the innate molecules that contain those same protein motifs too, evoking all sorts of damage to potentially many different tissues and organs. When there is structural similarity between the pathogen and immune cells, the process for immune activation is quite easy. The pathogen slips in, binds to a receptor and initiates the inflammatory immune response. In either case, the immune response to the environmental pathogen results in a disease process identified as autoimmune – the immune system attacking itself. It should be noted that connection between molecular mimicry and autoimmune disease onset is hotly debated.

Narcolepsy or Hypersomnia, the Immune System and the Flu Vaccine

In 2010, amidst the fears of the H1N1 swine flu pandemic, citizens in Scandinavia and Europe were given the adjuvanted (MF-59 a squalene based adjuvant plus ASO3 – squalene-α-tocopherol mix) flu vaccine called Pandemrix. Shortly thereafter physicians began noting an increase in new onset cases of narcolepsy, especially in Scandinavian children.

Narcolepsy is the lifelong disorder characterized by excessive sleepiness with abrupt and sudden transitions to REM sleep. It affects approximately ~ 1 in every 3000 individuals worldwide. Individuals with narcolepsy/hypersomnia have sudden and very strong urges to sleep throughout the day, though at night insomnia may develop. Patients may fall asleep as many as 20-30 times per day, for brief periods, making regular functioning difficult without wake stimulating medications.

Often co-occurring with narcolepsy is a condition called cataplexy. Cataplexy denotes the muscle tone and behavioral changes that precede the narcoleptic sleep incident. Cataplexy symptoms can range from the barely perceptible loss of facial muscle tone or twitches to full muscle paralysis and collapse. Approximately 70% of patients with narcolepsy also have cataplexy.

Hypersomnia, or more specifically, idiopathic hypersomnia, is a central nervous system disorder similar to narcolepsy. Like with narcolepsy, the brain is unable to regulate sleep-wake cycles, only here instead of bouts of uncontrollable sleepiness and periods of sudden onset sleep, with idiopathic hypersomnia, the sleepiness is severe, excessive and continuous. Both narcolepsy and idiopathic hypersomnia have long been thought to be autoimmune in nature, triggered by environmental factors. Bacterial infections such as streptococcus pyogenes, the bacteria responsible for strep throat/pharyngitis and skin infections like impetigo can elicit narcolepsy in some individuals, as well as autoimmune rheumatic fever and kidney disease in others.

Hypocretin/Orexin Neurons Damaged in Patients with Narcolepsy/Hypersomnia

From an autoimmune standpoint, key to triggering narcolepsy in some individuals, is presence of a particular gene variant in immune cells called human leukocyte antigens (HLA). The variant is labeled HLA -DQB1*0602. Fully 98% of patients with narcolepsy exhibit the DQ0602 haplotype (DQA1*0102/DQB1*0602) versus 18-25% of the general public who have the mutation but do not experience narcolepsy. DQ0602 impairs and often destroys the brain neurons that secrete a peptide hormone that is required to maintain wakefulness. The wake-promoting hormone released from the hypothalamus, is called orexin or hypocretin. Orexin and hypocretin are the same molecule that was discovered simultaneously by two separate research groups and then named independently. Readers will see research articles on both orexin and hypocretin linked to narcolepsy (and the flu vaccine, migraine, glucose metabolism, feeding behavior, to name but a few other areas of research).

Molecular Mimics in the Flu Vaccine Attack Hypocretin Neurons and Induce Narcolepsy

Researchers from Stanford found molecular mimics in the adjuvanted Flu vaccine, Pandemrix, both sequence code and structural similarities that initiated immune system attacks on the hypocretin/orexin system in narcolepsy patients but not healthy controls. It should be noted in this particular study, only the adjuvanted version of the flu vaccine was studied, as that was the product distributed in Europe and Scandinavia. The non-adjuvanted version of the Flu vaccine sold in the US was not tested.

For the present study: CD4+T Cell Autoimmunity to Hypocretin/Orexin and Cross-Reactivity to a 2009 H1N1 Influenza A Epitope in Narcolepsy, the researchers used confirmed narcolepsy patients and controls who were all positive for the DQB1*0602 gene variant associated with narcolepsy. Here, despite having the variant, only the patients had a reactivation of the immune attack on the hypocretin neurons. The control group, who were also positive for the variant, but who had no active symptoms or diagnoses of narcolepsy, did not demonstrate the same immune response. This suggests that other factors in addition to the molecular mimics and a personal predisposition must align to initiate the immune response or, in this case, what is deemed the autoimmune response. It also suggests, that in predisposed individuals, vaccine introduced molecular mimics can trigger immune system attacks and initiate disease states that may or may not have been symptomatic pre-exposure.

What this research does not explain is whether the new onset cases observed in the Scandinavian population post vaccine exposure were solely in individuals with the pre-disposing genetic variant. Was the increase in narcolepsy post flu vaccine exposure indicative of a latent disease state simply triggered by the vaccine? Or is it possible that there are other molecular mimics embedded within the flu vaccine, not yet identified, that might also trigger narcolepsy? Finally, and most importantly, could there be additional factors native to this and other vaccines, to the individual, or with the combination thereof, that evoke an attack on the neurons responsible for regulating wakefulness and inducing narcolepsy, or evoke an attack on other cells and elicit different disease processes? If the answer is yes to any of these questions, then our approach to vaccines ought to be rethought.

Molecular Mimicry and the HPV Vaccines Gardasil and Cervarix

Here is where it gets interesting for those interested in post Gardasil injury. The flu study, as limited and focused as it was, provides important clues to how and why the HPV vaccine might also induce an array of side effects, including, but not limited, to hypersomnia in some individuals but not in others.

Researchers have begun investigating molecular mimics in the HPV vaccines Gardasil and Cervarix. Thus far, they have identified 82 pentamer (5) level mimics and 34 heptamer (7) level mimics in the HPV 16L component. The offending motifs control a variety of cell behaviors related to cardiac functioning, cell permeability and cell death. An immune system attack on any of these motifs could elicit serious illness. Indeed, the researcher postulates that the mimicked motifs controlling cardiac functioning could be culprits in the post HPV vaccine incidences of sudden death.

To my knowledge, the full HPV vaccine to human proteome has not been mapped and so how or if there are mimicked protein motifs within the HPV vaccine that are capable of attacking the hypocretin/orexin neurons is not known. Nevertheless, idiopathic hypersomnia, a derivative of narcolepsy, is one of the core symptoms of post Gardasil injury, though it is sometimes misdiagnosed and mischaracterized as excessive fatigue and sleepiness. Additionally, a number of other symptoms post Gardasil are influenced by the hypocretin/orexin system, including feeding behavior, gastroparesis (perhaps via galanin) migraine, and all over pain (via dynorphin) – more on this in subsequent posts. Since we now know that molecular mimics can evoke reactions, it is only a matter of time before researchers match the vaccine protein motifs and structural homologies to individual gene variants, environmental predispositions and the clinical symptoms/syndromes that develop.

Perhaps even more interesting, when we dig into the hypocretin/orexin system we see that the neurons are especially susceptible to changes in ATP. Intracellular ATP in hypocretin/orexin neurons must be maintained at much higher levels than in other cells. Diminished ATP stores inhibits hypocretin/orexin firing and thereby reduces sustained wakefulness. We know from other research and patient reports that severe thiamine deficiencies are present in post Gardasil injury (whether the deficiencies existed pre-Gardasil, but were asymptomatic is not clear). Thiamine is a required co-factor in the production of ATP. Reduced thiamine would impair functioning in the hypocretin/orexin neurons and induce the hypersomina and hypophagia and many of the other symptoms we see post vaccine.

In subsequent papers, I will explore the myriad functions the hypocretin/orexin neurons regulate and how damage to those neurons, either directly as indicated in the flu vaccine study, or indirectly, via targeting critical co-factors provides clues to the constellation of post Gardasil injuries. Additionally, I will address the molecular mimicry debate and how it will reshape the framework for understanding autoimmunity.