The paradoxes of Lyme vaccines, pt. 1

In practical terms, Lyme vaccination is easy and impossible

Source: Canva image generator output.

A Summary:

A Lyme Disease vaccine turns out to be a remarkably simple and yet complex problem, one that was both solved and not-solved in 1998. This post will read as warm to the idea of an effective Lyme vaccine, but is meant to focus on aspects of the problem which are hopefully of interest even to those who would consider even an effective Lyme vaccine useless or dangerous on principle: It explores the question of “What makes for a vaccine that the medical establishment doesn’t like?”

• A fairly effective vaccine against Lyme Disease in America is possible and was created in 1998 based on immunization with a single antigen of the Borrelia burgdorferi (Bb) bacteria (in Europe the problem is more complex, because many strains of Borrelia are prevalent). This antigen is the “OspA” lipoprotein, which is expressed in the life cycle of Borrelia when nymph ticks begin to feed on the host.

• Brilliantly, the vaccine works by destroying Bb inside the tick, as antibodies travel with the blood into the gut of the tick as it just begins to feed. The bacteria is killed while still in the stage expressing OspA, before it becomes more dynamic, diffused, and difficult to eliminate. In other words — leaving aside that other infectious agents within the tick are not eliminated by the vaccine and may still cause some symptoms — the solution to Lyme in America is incredibly simple: Just have a lot of antibodies against Bb-OspA, and the blood turns into “medicine” that kills Borrelia inside the tick.

• This also leads to the primary limitation of Lyme vaccines: Since Borrelia never enters the body, there is no “natural boost” even when caught by an infected tick. Regardless of tick exposure, antibodies quickly wane to levels that render ingested blood safe for Borrelia within a future infected tick. Protection from a primary course of Bb-OspA-based vaccine barely lasts a single Lyme season; protection in the long term would require a yearly booster.

• Further, challenge with a Bb-infected tick when vaccine antibodies are on the wane, allowing Borrelia to still invade, may worsen disease outcomes by enhancing immune and inflammatory reactions. The “silver bullet” of the OspA vaccine thus turns into a ticking time-bomb after the first few months. (This may be true for arthritic symptoms while, in theory, for cardiac and neurological complications, low antibodies are still protective overall. In any case long-term outcomes for individuals vaccinated before the licensed vaccine, GSK’s LYMErix, was withdrawn do not appear to have been studied.)

• There are other practical limitations which may ensure that Bb-OspA-vaccination remains an unavailable and virtually unknown “silver bullet”:

  • The GSK vaccine became controversial, and was ultimately withdrawn, due to fears that it caused Lyme symptoms based on molecular mimicry and autoimmune reactions, and was beset with lawsuits as a result; although these fears were based on only 4 case reports involving only short-term symptoms, and theories which have not found confirmation in animal models or epidemiological investigations, they would present a financial headwind to any future vaccine. The FDA might respond to attempts to re-issue the GSK vaccine by calling for new Phase III trials, or the release of currently private post-marketing data from GSK. Meanwhile, other candidate vaccines are either pursuing more difficult approaches to the problem or have become mired in “development hell” due to financial and other headwinds.¹

  • CDC and physician support for the GSK vaccine was lukewarm despite a successful trial, in part because many physicians are skeptical of the relevance of Lyme Disease, believing treatment with antibiotics to be easy and effective.

  • Ironically, the Lyme Disease advocacy organizations also offered opposition to the GSK vaccine, helping to fuel the post-vaccine-Lyme claims. These groups appear invested in the idea that Lyme Disease is too complex to be solvable by any means besides long-term attention and treatment. It is certainly possible (in theory) that advocacy groups devoted to “open-ended” treatment of Lyme Disease view effective Lyme vaccination as a financial threat.² Such groups may also have personal and financial associations with individuals who experienced health complications (seemingly or actually) due to vaccines, and as such are conflicted on the notion of prevention.

  • Thus, Lyme Disease is considered not worth preventing either because it is seen as not a serious problem, or as a problem too intractable (and lucrative?) to allow anyone to solve. It is unclear whether either of these groups would have changed their attitudes in the last 20 years, meaning any future vaccine would end up in the same regulatory and financial limbo as LYMErix.

Lyme Disease: from the human, tick, and author perspective

“Lyme Disease” describes, in one sense, a set of confusing patient complaints that either follow a clinically recognized and treated tick-borne infection, or are retroactively attributed to such an infection. The former condition is typically an acute and treatment-limited condition featuring fever, and rashes and arthritic aches which may disseminate throughout the body, and where, especially in absence of treatment, serious cardiac and neurological complications are of substantial risk in ensuing weeks due to systemic infection in the absence of an immune response. Even with treatment some infections will result in long-term symptoms including but not limited to arthritis and depression; and at this point (auto-)immune responses may be exclusively responsible or may share etiology with persistent infection of one or several of the organisms introduced by the original tick bite. In such case patients are in fraternity with the latter group originally described, whose long-term symptoms are only attributed to a tick-borne infection on the basis, typically, of antibody responses to the same organisms.

This is perhaps the most vague way to describe Lyme, but it is also accurate from the clinical and epidemiological standpoint — “Lyme Disease” is a description attached to different experiences, and the provenance of that description is subjective. This is true of any infectious disease, but Lyme is beset by a host of of diagnostic impairments: It typically results from bites from nymph stage ticks, and as such the bites are not usually noticed until infection is underway and the rash develops, if even then; these same bites transmit more than one infectious agent, so that although Borrelia is the primary cause of symptoms, co-infection with other organisms may exacerbate or cause separate symptoms; and Borrelia and the co-infecting organisms are not especially amenable to lab diagnosis. The result is that many infections go unrecognized even when patients present with symptoms, and many recognized cases are controversial as they are made according to different standards of care and may not be based on positive laboratory evidence of infection. For decades, in fact, patients with long-term symptoms have tended to “shop around” for doctors who will affirm Lyme — but even this will be subjective and vary from patient to patient. Thus when one describes “Lyme Disease” in either a clinical or epidemiological setting, one is describing a set of conditions that includes many false negatives and some false positives as well. For example, with enough persistence, it is not impossible that someone simply experiencing depression can get themselves counted as a case of L

That’s the human point of view.

The tick’s view

If we take the tick’s perspective, things are simpler, and this is a better route to understanding the impact of the disease on humans.

Ticks want to suck blood. Ticks in the northeast and Great Lakes-area rampantly harbor nasty pathogens, particularly Borrelia burgdorferi (Bb).

This spirochete bacteria spreads from nymph ticks into bitten humans typically before the host even realizes they have a feeding tick; the circular rash that Bb causes is the first noticed symptom, though in some cases it goes unnoticed or does not appear. Afterward, Bb (and maybe some co-infecting pathogens) disseminates through the blood and disperses throughout the body in the absence of an immune response. It may invade the heart or brain, leading to sudden pathologies in these organs in the weeks after infection, especially if the bite and infection still go unnoticed and untreated. In some percentage of infected humans, infection leads to persistent and difficult-to-treat symptoms, including arthritis and depressive symptoms; the host is turned into a Chronic-Illness-Haver, a pariah of mainstream doctors and cash-cow for more sympathetic physicians and advocacy organizations; a parasite on their families and society at large.

This could be you. sufferingthesilence.com

This happens, in all likelihood, to 100,000s of Americans every year. For residents of areas with substantial risk of tick exposure (it is estimated that in some areas, ≥1% of residents are infected annually), the risk of time spent in nature can be mitigated partly by prevention such as insect repellent, but in practical terms this is less help for the risk of exposure in home and neighborhood outdoor spaces. For whatever reason, in fact, the problem seems to be getting worse. And when infection with Bb happens, infected hosts are suddenly beset by a disease that may evade diagnosis and appropriate treatment; the true rate at which early treatment fails to occur is unknown for precisely the same reasons that make diagnosis difficult.

Bb is a pernicious invader; it wants to spread back to future ticks, and thus has adaptations to mammalian immune challenges which make persistent infection likely. Bb forms intracellular reservoirs in many types of cells, and extracellular reservoirs in eyes, joints, and the Central Nervous System. Although Bb is extremely vulnerable to OspA-antibody in the early tick stage of its lifecycle, it rotates gene expression to other lipoproteins by the time it has moved to the mammalian host. While considered easily treatable by antibiotics per the orthodox medical standpoint (and again, this would only apply to the portion of infected individuals who receive prompt treatment), the sophisticated array of expressible genes and plasmids in the Bb genome suggests that some bacteria may possess resistance. In either case, Bb also has a capsid phase which further “seeds” immune- and antibiotic-resistant reservoirs of persistent infection.

In fact, despite the difficulty of confirming persistent infections in the lab, it is plausible that nearly all Bb infections lead to persistent reservoirs, and that many late-developing symptoms are mistaken for “aging” and never diagnosed as Lyme.

Long-term manifestations of Lyme disease may be a result of such persistent infections, or a “gift” of auto-immunity conferred by antigenic properties of Bb. In either case they are difficult to treat, especially as detecting Bb after acute infection is difficult and co-infecting organisms may also be contributing to symptoms — and once again this difficulty itself is a source of much uncertainty regarding how Bb causes these long-term symptoms.

The author’s view

I don’t want to be infected by Borrelia burgdorferi; I especially do not want to ever have the bad luck of persistent post-Lyme symptoms.

Currently, I have the “luck” of living in California (where a bigger concern is exposure to such things as louses from the homeless who use every fast-food restaurant and gym) — but I grew up on the east coast of Virginia, which is a Lyme hotspot.

Since being brought to the attention of the medical community and then the media and public, fears of Lyme have been in disproportion to its impact relative to other maladies. But this is because persistent Lyme Disease, much like polio, is horrifying — it cripples the afflicted, and modern medicine can neither cure the afflicted nor explain why they, in particular, were “chosen.” My own concern for Lyme stands in contrast to my attitude to the complications of common infectious diseases, especially childhood illnesses. I have a high risk tolerance for these illnesses because I believe that they are part of normal development. Persistent viral infections leading to chronic disease and disability are real; but I don’t think vaccines can ever offer a true remedy to this risk — there will always be other viruses. I don’t view tick-borne infection with tiny, screw-shaped bacteria that like to live inside of cells, and possibly become lifelong parasites, potentially turning people into chronic patients at any age of life, as part of the same “normal.” Actually, it is nightmarish.

In fact, I have come to suspect that I did experience Lyme while living in Virginia. In high school, I came down with a severe bout of muscle and joint pain in my legs, which lasted one or two weeks. During this time, all I could do was lie still and try to distract my mind from the agony.

This took place after my first few weeks of running cross country, particularly after an intense run in the state park we used for practice — I was never able to see a doctor for this. While it self-resolved (though only after eventually “running through the pain”), I have always been over-susceptible to joint pain in my legs since that illness. Of course, this itself could simply be from having continued to run cross country in high school; certainly that is how I used to interpret the problem.

It is true that the same ticks which transmit Borrelia may also transmit other pathogens that cause short and long-term illness, protection against Borrelia ever making its way into my body is something that, if I still lived where there is an exposure risk, I would want. If that protection could be attained simply by having antibodies against OspA — and not be subject to the paradoxes which are the topic of this post —

I would make use of it!

Hence my interest in the paradoxes of Lyme vaccination.

The GSK vaccine was withdrawn in 2002 due to reputational misfortunes. But the promise that it represents — a single-antigen vaccine that kills Borrelia within the tick, preventing it from ever entering the body — is fantastic. Yet, in fact, it is almost impossible that such a vaccine will ever be available or practically effective.

Another way?

Part two, if I write it, will discuss the paradoxes of the Lyme vaccine in slightly more detail than provided in the summary above, and give thoughts on the feasibility of a future vaccine (which at least adults in risk areas could use at their own discretion). However, this would only be done to flesh out the complicated picture of the problem already provided; since that would be a bit tedious, I may leave this post as a stand-alone.

In case I do, I will throw in one idea which occurred to me in researching the Lyme vaccine problem: If long term protection from serum antibodies is impossible (without annual or higher-potency vaccines, both of which might be more prone to harmful effects), perhaps protection can be attained by inducing sensitivity to tick bites — especially by IgE allergic sensitization. If nymph tick bites could be noticed as soon as they start, not only Borrelia but other co-infections associated with Lyme could be prevented. This itself sounds like a dangerous track, with substantial risk of cross-reactions, but it is an interesting possible escape from the paradoxes of anti-Borrelia vaccination.

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1. Plotkin, SA. (2018.) “Lemons and Lyme.” Pediatric Infect Dis Soc. 2018 Dec 3;7(4):267-269. doi: 10.1093/jpids/piy083.

2. Almost all claims in this post are derived from multiple sources and are treated as common knowledge; a general bibliography is provided below. Regarding the influence and motives of Lyme Disease advocacy organizations, I must cite Stanley Plotkin’s manifesto, above. Supporting his claim, in a partly satisfactory manner, is the fact that RB Stricker, who represents the patient-centric, pro-“open-ended treatment” International Lyme and Associated Diseases Society, is cited in the bibliography below in two papers, one of which is a criticism of orthodox medical attitudes regarding the ease of treatment of Lyme, and the second of which is an attack on a later candidate vaccine based on affirmation of safety fears regarding LYMErix.

General bibliography for this post:

The biology of Lyme Disease and OspA-vaccination:

Stricker, RB. Lautin, A. Burrascano, JJ. (2005.) “Lyme disease: point/counterpoint.” Expert Rev Anti Infect Ther. 2005 Apr;3(2):155-65. doi: 10.1586/14787210.3.2.155.

Hanson, MS. Edelman, R. (2003.) “Progress and controversy surrounding vaccines against Lyme disease.” Expert Rev Vaccines. 2003 Oct;2(5):683-703. doi: 10.1586/14760584.2.5.683.

Steere, AC. (2001.) “Lyme Disease.” N Engl J Med. 2001 Jul 12;345(2):115-25. doi: 10.1056/NEJM200107123450207.

The LD-patient-advocacy argument against LYMErix:

Stricker, RB. Johnson, L. (2014.) “Lyme disease vaccination: safety first.” Lancet Infect Dis. 2014 Jan;14(1):12.

Lack of support for safety fears regarding LYMErix:

Ball, R. et al. (2009.) “HLA Type and Immune Response to Borrelia burgdorferi Outer Surface Protein A in People in Whom Arthritis Developed After Lyme Disease Vaccination.” Arthritis Rheum. 2009 Apr; 60(4): 1179–1186.

Lathrop, SL. et al. (2002.) “Adverse event reports following vaccination for Lyme disease: December 1998-July 2000.” Vaccine. 2002 Feb 22;20(11-12):1603-8. doi: 10.1016/s0264-410x(01)00500-x.

I include both these links for completeness. Both involved authors from the FDA, which the reader may consider an implicit conflict of interest against revealing harms from an FDA-approved vaccine. However, this post does not litigate the safety of LYMErix or any potential OspA-based vaccine.

The epidemiology of Lyme Disease:

CDC Surveillance: Lyme Disease Note that the CDC revised the criteria for reporting Lyme in 2022, resulting in a substantial increase in recorded cases, especially in New York — however, this increase may also reflect real changes in the disease.

“Justin Bieber’s Reveal Shows Why Lyme Disease Is Often Misdiagnosed” healthline.com (Encountered while exploring why google trends shows a spike for “Lyme” in early 2020; it is a good overview.)

“Tick season is off to record start in New York, Northeast. Why is it so bad?” Democrat and Chronicle.