Lyme disease vaccine in clinical trials – good news for everyone

Even though dogs have access to a Lyme disease vaccine, there has not been a vaccine available for humans for 18 years. But that’s about to change, considering how much the tick responsible for the disease has spread.

Just to be clear, vaccine manufacturers do not value dogs more than humans for a Lyme disease vaccine. In reality, the blame for why there isn’t a Lyme disease vaccine can be placed right where some of you expect it to be – loud-mouthed, misinformed anti-vaccine zealots who lacked any scientific evidence supporting their claims.

Of course, the issues with the original Lyme disease vaccine happened in the mid-1990s, and the internet was in its infancy (hello AltaVista). But there were people pushing the same narrative that we hear about the cancer-preventing HPV vaccine – they claimed, without any scientific evidence, that the Lyme disease vaccine was actually worse than the disease itself.

That certainly sounds familiar!

But a new Lyme disease vaccine might be on its way fairly soon. That means adults and children can run in the grass, go hiking, and generally enjoy the outdoors without worrying about this debilitating disease.

Lyme disease vaccine
Your dog can get the Lyme disease vaccine, thanks to the anti-vaxxers. Photo by Oscar Sutton on Unsplash.

What is Lyme disease?

Lyme disease is an infectious disease caused by at least three species of bacteria belonging to the genus Borrelia. Of the three species, Borrelia burgdorferi is the main cause of Lyme disease in North America, whereas Borrelia afzelii and Borrelia garinii are more prevalent in Europe. The disease was named after the towns of Lyme and Old Lyme, Connecticut, where a number of cases were initially identified in 1975.

Borrelia is transmitted to humans when bitten by infected ticks which belong to a few species of the genus Ixodes, called “hard-bodied” ticks. Although deer ticks, Ixodes scapularis, Ixodes pacificus, or Ixodes ricinus, are commonly considered to be the vectors for Borrelia infection, some of the other species in the Ixodes genus can transmit the disease. Lyme disease is the most common tick-borne disease in the United States.

There are several initial symptoms of Lyme disease – fever, headache, fatigue, depression, and a circular skin rash called erythema migrans (EM). If the Borrelia infection is not treated quickly, further symptoms may appear that can involve the joints, heart, and central nervous system.

There is generally only one known treatment for a Borrelia infection – antibiotics, which may include doxycycline, amoxicillin, and cefuroxime. Generally, the symptoms of the infection resolve after antibiotic treatment.

As I’ve written previously, the existence of “chronic Lyme disease,” a condition which some claim is a set of vague symptoms that are a consequence of a permanent B. burgdorferi infection and somehow persists after antibiotic therapy. The existence of chronic Lyme disease is not supported by robust scientific evidence published in peer-reviewed, high impact-factor biomedical journals.

Not real scientists not working on the lyme disease vaccine.

All about the Lyme disease vaccine

The only FDA approved Lyme disease vaccine, LYMErix, was developed by SmithKlineBeecham (known now as GlaxoSmithKline) and introduced to the US market in 1998. Patients were given a three-dose series of the vaccine over a few months.

The vaccine worked in a unique way – it stimulated antibodies that attacked B. burgdorferi bacteria in the tick’s gut as the tick was feeding on the human host. Thus, the bacteria were attacked before they were able to enter the human body. It was about 78% effective in preventing Lyme disease after all three doses were given. Better yet, the vaccine was also shown to be nearly 100% effective at preventing asymptomatic cases of Lyme disease, where an individual would get the disease and develop antibodies against it but never develop any symptoms.

In 2002, SmithKlineBeecham withdrew the vaccine from the market, and Pasteur Mérieux Connaught, who also had a Lyme disease vaccine, decided to withdraw its application to the FDA, despite showing safety and effectiveness in a Phase III clinical trial.

So what happened to the human Lyme disease vaccine?

The Lyme disease vaccine sold very well after it was introduced in 1998. Because of the fear of Lyme disease, the vaccine received a lot of positive press and many people demanded the vaccine for themselves and their children (how refreshing that would be). There were numerous news stories (back when our news stories came from magazines, newspapers, and evening news reports).

However, within a year, the anti-vaccine forces got to work, passing along accounts regarding serious adverse effects – in other words, more anecdotes. Patients who received the vaccine claimed a wide variety of side effects – musculoskeletal complaints, like arthritis, dominated the maladies caused by the vaccine.

Of course, the media, who were extolling the virtues of the vaccine just a few months prior, switched to carrying news stories of the “victims” of the vaccine. The Lyme Disease Network devoted their website to coverage of controversies surrounding the vaccine. 

In other words, the same narratives we hear today about every single vaccine, all of which lack scientific evidence.

Enter VAERS

Between December 28, 1998, and July 31, 2000, nearly 1.5 million doses of the Lyme disease vaccine had been given to patients in high-risk areas of the USA. During that same time, there were over 905 reports were made to the Vaccine Adverse Event Reporting System  (VAERS) about adverse events after the administration of the Lyme disease vaccine.

As I’ve written previously, VAERS is a passive system where individuals can report supposed adverse events post-vaccination. And the anti-vaccine nut jobs love to dumpster dive into the database and use it as evidentiary proof of links between vaccines and a whole host of adverse events. 

The most important point is that there are no investigations to show any type of causality between the vaccination event and the claimed adverse events that are reported to the VAERS database. The VAERS system itself says that the data cannot be used to ascertain the difference between coincidence and true causality.

Furthermore, there is a background rate for all adverse events, including mortality, across all causes, irrespective of vaccination status.  Unless you understand this adverse event background rate, the vaccine adverse event rate has no scientific meaning.

Of the 905 Lyme disease vaccine reports to VAERS, 66 were considered serious adverse events – they either resulted in life-threatening illness, hospitalization or disability. However, researchers examined the reports, and concluded that they “did not detect unexpected or unusual patterns of reported adverse events.” The researchers showed that the VAERS data did not support the hypothesis that the events were caused by the vaccine and that the events did not occur at a higher than expected background rate regardless of Lyme disease vaccination status.

In other words, they could establish no difference in the rate of these so-called “adverse events” between unvaccinated and vaccinated populations. Once again, you’ve probably seen this lack of difference in almost every vaccine on the market. 

There was a potential issue where individuals might be susceptible to a type of immune cross-reactivity that causes arthritis. These individuals may have a gene that can cause this type of arthritis. However, it is extremely rare, and this cross-reactivity could possibly occur with the Borrelia infection. However, a causal relationship between the vaccine and this type of arthritis has never been supported by scientific evidence.

Enter the lawyers against the Lyme disease vaccine

In December 1999, a Philadelphia law firm, motivated by the public concern over the vaccine’s safety profile, filed a class-action lawsuit against SmithKlineBeecham regarding the safety of the LYMErix vaccine. The law firm, Sheller, Ludwig & Bailey, represented 121 individuals who claimed that they experienced significant adverse reactions after receiving the Lyme disease vaccine.

Now, those of you who are familiar with vaccine lawsuits will probably ask, “why wasn’t this vaccine covered by the National Vaccine Injury Compensation Program (NVICP)?” The NVICP is a program where a $0.75 tax is placed on every dose of vaccine and is used to compensate “victims” where causality between the vaccine and a serious adverse event can be shown. However, the program only covers vaccines that are recommended by the CDC, which includes most childhood vaccines.

The Lyme disease vaccine has a permissive recommendation, meaning that physicians must decide if a patient might be at risk for getting the tick bite, to determine if they receive the vaccine. A hiker who slogs through trails in the woods of the Northeast is at a higher risk of the disease than an office worker in Arizona, so the former would get the vaccine and the latter probably won’t. The vaccine was excluded from the NVICP program because it was not recommended for general use (see Note 1).

The anti-vaxxers kill the Lyme disease vaccine

In the meantime, Dr. Gregory Poland, a vaccine scientists at the prestigious Mayo Clinic and who was a strong advocate for the Lyme disease vaccine, was threatened by these anti-vaccine advocates (we’ve definitely heard this before). Clearly, the tactics of the anti-vaccine activists haven’t changed over the past 20 years. Things were getting serious.

According to Nigrovic and Thompson, the FDA had to get involved:

With lawsuits pending and questions from the public and the media, and facing an increasingly complex and explosive situation, the FDA reconvened its advisory panel on 31 January 2001 to discuss the future of the Lyme vaccine. The participants included the FDA scientific advisors, the LYMErix™ manufacturer, independent experts, practising physicians, the ‘vaccine victims’ and their lawyers.

This panel, described by one participant as raucous and riotous, provided a forum for all of the stakeholders. In support of the vaccine, the FDA summarized the VAERS data and concluded that the evidence did not support a causative association. The vaccine manufacturer, now GlaxoSmithKline following a corporate merger, assured the assembled parties that the LYMErix™ vaccine did not cause harm to its recipients. They reviewed the status of their phase IV post-marketing surveillance. Practising physicians spoke of vaccine efficacy by describing the dramatic reduction in Lyme disease cases in their own practices.

As a result of this meeting, bad press, more lawsuits, and declining sales, GlaxoSmithKline withdrew the vaccine from the market in 2002.

Nigrovic and Thompson concluded that,

The complicated history of LYMErix™ provides important lessons. Although the FDA did not revoke the licence, the manufacturer withdrew the product amidst falling sales, extensive media coverage, and ongoing litigation, even though studies indicated the vaccine represented a cost-effective public health intervention for people at high risk of acquiring Lyme disease.

Although preliminary evidence supported LYMErix™ safety, product withdrawal precluded completion of more definitive studies. In the wake of the scientifically justified withdrawal of the rotavirus vaccine, LYMErix™ entered the market at a time of extremely low public tolerance for vaccine risk. Nonetheless, in the absence of a Lyme vaccine, the incidence of B. burgdorferi infection continues to be ∼20 000 case per year in the United States with thousands of additional cases occurring globally.

Mother Jones, in a recent article, made it clear – blame the anti-vaxxers for the lack of a Lyme disease vaccine.

Influenced by now-discredited research purporting to show a link between the MMR vaccine and autism, activists raised the question of whether the Lyme disease vaccine could cause arthritis. Media coverage and the anti-Lyme-vaccination groups gave a voice to those who believed their pain was due to the vaccine, and public support for the vaccine declined.

“The chronic arthritis was not associated with Lyme,” says Stanley Plotkin, an adviser to pharmaceutical company Sanofi Pasteur. “When you’re dealing with adults, all kinds of things happen to them. They get arthritis, they get strokes, heart attacks. So unless you have a control group, you’re in la-la land.”

Not a photo of VLA15.

Good news!

Despite all of that nonsense, we still need a Lyme disease vaccine. According to a Nature editorial,

It may go against the scientific grain for marketing considerations to play such a part in steering vaccine development. But in the real world, this may be unavoidable. Lyme disease is a serious illness and those who live in areas where it is spreading deserve a vaccine.

Fortunately, French vaccine developer, Valneva, has been developing a new Lyme disease vaccine, code-named VLA15. According to Valneva’s website, VLA 15 is a multivalent vaccine that targets one of the most dominant outer surface proteins of Borrelia. 

Preclinical studies showed that the vaccine was broadly effective against Borrelia. Phase 1 clinical trials, in which the vaccine is tested on healthy volunteers, were successful and Valneva is proceeding with Phase 2 clinical trials.  

According to the National Institutes of Health clinical trial database, which tracks all clinical trials across the world that must be registered through the FDA, there are two Phase 2 clinical trials underway for VLA15:

  • A randomized, observer-blind, placebo-controlled, multicenter Phase 2 study which will include 570 patients, ages 18-65. At least this study will satisfy those anti-vaxxers who whine complain constantly about the lack of placebo controls in many vaccine studies. Because this new Lyme disease vaccine lacks any antecedent vaccine (it’s off the market), it is ethical to run a placebo-controlled study. The study will be located in Stamford, Connecticut (USA), Binghamton, Rochester, and Endwell, NY (USA), Warwick, RI (USA), Ghent, Belgium, and Berlin and Hamburg, Germany. 
  • A second randomized, observer-blind, placebo-controlled, multicenter Phase 2 study is also planned – this one is to examine the vaccine schedule, another important consideration (and will probably be used as evidence by the CDC to establish a schedule for the vaccine). This study will include 250 patients, ages 18-65. This study will be located in Stamford and Milford, CT and in Rochester, Binghamton, and Endwell, NY. 

If you want to volunteer, and you live in those locations, you can ask to be recruited by contacting the lead physician in the location by clicking on the links above to the clinical trials. However, you need to meet all of the qualifications (which are listed in the same links), and even then there will be a lot more volunteers than they probably can handle. And no, you don’t get to choose which group in which you’ll be included – that defeats the whole point of “blinded.”

If I lived in those areas, I would love to get into the study, but I couldn’t write about here. Participants are usually required to sign pretty strong non-disclosure agreements, so you can’t post on Facebook how you were bitten 10 times by a tick and never got Lyme disease.

Finally, VLA 15 was granted a Fast Track designation by the FDA in July 2017. Because this designation is often misunderstood, I’ll try to explain it. Fast Track is granted by the FDA to investigational products that are under development for serious conditions and have the potential to fulfill an unmet medical need (in other words, the Lyme disease vaccine is a perfect example).

The process facilitates the clinical development and expedites the review of new drugs and vaccines. It accelerates the availability of promising products on the market.

This does not mean that the vaccine gets less than a thorough review. It does not mean that Valneva can skip any of the phases of human clinical trials. Fast Track speeds up the review process. The process does not become easier.

Valneva had recruited approximately 180 healthy volunteers at three centers – two in the US and one in Belgium – for its Phase I clinical trials. The primary objective of the observer-blind, partially randomized, dose-escalation study was to evaluate the vaccine candidate´s safety and tolerability profile at different dose levels and formulations.

The study had also measure immunogenicity, by observing the number of antibodies formed against the six most prevalent serotypes of Lyme disease. Valneva will also monitor different dose groups and formulations at different time-points.

The vaccine completed the Phase I clinical trial in early 2018. The results have not been published in a peer-reviewed journal yet, but the results were submitted to the FDA (and probably the European Medicines Agency). Those results received thorough review before approval was granted to begin recruiting for a Phase 2 clinical trial.

According to Valneva,

Phase I study (VLA15-101) primary endpoint met
• No safety concerns associated with VLA15 in any treatment group
Encouraging immunogenicity with VLA15
• VLA15 is immunogenic in all doses and formulations tested

Valneva did run what they call a Phase 1/2 study, not sure what that is, but it included 1630 patients in Europe. The study was performed to compare the vaccine with aluminum adjuvant versus no adjuvant (and here come the anti-vaccine activists).

This study has also not been published yet, as far as I can tell. The results would be certainly interesting for both preventing Lyme disease and data comparing aluminum in vaccines.

Even though the vaccine has a “Fast Track designation,” that doesn’t negate the need for Phase I, II, and III clinical trials. It still will be several years before the vaccine becomes available, so be patient. Unless, of course, you can talk yourself into the vaccine arm of the clinical trials, then you can feel protected against Lyme disease.

On the other hand, your dog can get the Lyme disease vaccine.

Notes

  1. Imagine the response from the anti-vaccine religion if the CDC added the vaccine to the recommended schedule – Twitter might break from all of the nasty comments. At this time, Lyme disease is mostly prevalent in the Northeast along with the mid-Atlantic and upper Midwest. However, there have been reports of Lyme disease from many other states, since the Ioxedes tick has been found in many counties outside of the traditional Lyme disease areas, putting these counties at risk of outbreaks of the disease. I could make an argument that the vaccine should be recommended in certain regions of the USA at a minimum.

Editor’s note – this article was first published on July 2017. The feathery dinosaur had to do some copyediting, updating links, and performing some other magic. Also, there has been a lot of updates to clinical trials that needed to be included. 

Citations



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The Original Skeptical Raptor
Chief Executive Officer at SkepticalRaptor
Lifetime lover of science, especially biomedical research. Spent years in academics, business development, research, and traveling the world shilling for Big Pharma. I love sports, mostly college basketball and football, hockey, and baseball. I enjoy great food and intelligent conversation. And a delicious morning coffee!

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