Lyme disease vaccine on the way – if only the anti-vaxxers stay away

Over the past decade, Lyme disease has spread from its traditional confines of the northeast USA to throughout the country. Even though dogs have access to a Lyme disease vaccine, there have not been any available for humans for 18 years. But that’s about to change.

Vaccine manufacturers do not value dogs more than humans for this vaccine. In reality, the blame for why there isn’t a Lyme disease vaccine for children can be placed right where some of you expect it to be – loud-mouthed anti-vaxxers without any scientific evidence supporting their hatred of the vaccine.

Of course, this happened in the mid-1990s, and the internet was in its infancy. But there were people pushing the same narrative that we hear about the cancer preventing HPV vaccine – that the Lyme vaccine was actually worse than the disease itself. They made these claims based on bad or no evidence.

But a new lyme disease vaccine might be on its way fairly soon. This is good news.

What is Lyme disease?

Lyme disease is an infection diseases caused by at least three species of bacteria belonging to the 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 is 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 belonging 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 involved 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 consequence of a permanent B. burgdorferi infection, which somehow continues after antibiotic therapy. People claim that this chronic infection results in a set of vague symptoms. These claims are  unsupported by robust scientific evidence.

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. The patients were given a three-dose series of the vaccine. 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 it’s 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 vaccine sold very well after introduction in 1998. Because of the fear of Lyme disease, the vaccine received a lot of positive press. Many morning and evening network news shows showcased the vaccine.

However, within a year, the anti-vaccine forces got to work, passing along accounts regarding serious adverse effects. Patients who received the vaccine claimed a wide variety of side effects, musculoskeletal complaints, like arthritis, dominated the complaints.

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.

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 corps dumpster dive into the database, and use it as evidentiary proof of links between vaccines and adverse events. Most reports are sent online. However, VAERS accepts fax or mail reports.

The most important point is that there are no investigations to show any type of causality between the vaccination event and the claimed mortality 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 a 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 rate regardless of Lyme disease vaccination status.

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 may cause this type of arthritis. However, it is extremely rare, and it may be possible that the cross-reactivity could occur with the Lyme infection. However, this causal relationship is unsupported by scientific evidence.

Enter the lawyers

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 LYMErix safety. 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 vaccinologist at the prestigious Mayo Clinic and who was a strong advocate for the Lyme disease vaccine, was threatened by these anti-vaccine advocates. 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.”

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 announced this week that its multi-valent Lyme disease vaccine, VLA15, was granted vaccine “Fast Track” designation by the US Food and Drug Administration.

The Fast Track designation 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. 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 a less than 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 has 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 is to evaluate the vaccine candidate´s safety and tolerability profile at different dose levels and formulations.

The study will also measure immunogenicity, by observing the quantity 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.

If I could give a bit of advice to Valneva – prepare for the withering anti-science and pseudoscience attacks from the anti-vaccine forces. Look to how Merck stands behind Gardasil9, despite the increasingly shrill rhetoric against the cancer preventing vaccine.

Humans deserve a Lyme disease vaccine that protects adults and children. Since the Lyme-carrying ticks are spreading into areas of the USA and Europe where they weren’t seen before, so the need for a vaccine is probably stronger than it was 20 years ago. 

Update 24 May 2018

As we get into the Lyme disease portion of the calendar, when people are outdoors enjoying the weather by hiking, camping, and going to areas where the Ioxedes ticks are out enjoying the weather themselves. It’s time to update the reader on the progress of the Valneva Lyme disease vaccine.

The vaccine just completed the Phase I clinical trial, which is first of three clinical trials necessary to get approval from drug regulators across the world. According to the Valneva website,

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

This was a Phase I clinical trial, which means it’s not blinded – it’s more to see if the drug is safe and effective in healthy volunteers. And it only included 179 adults in Europe and the USA. We’ll probably have to wait a year for a peer-reviewed article to be published where we can examine the results more carefully.

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 without. The study hasn’t 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 vaccines has “Fast Track Status,” 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. Of course, your dog can get the 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 only widely prevalent in the Northeast along with the mid-Atlantic and upper Midwest (pdf). 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 on the recommended for certain regions of the country at a minimum.
  2. Editor’s note – this article was first published in July 2017. The feathery dinosaur had to do some copyediting, updating links, and performing some other magic. Also, a section was added to update current progress in the vaccine.

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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!