Lyme disease vaccine – good for dogs but not for humans

If you go to your veterinarian to get the Lyme disease vaccine for your dog, just make an appointment and your dog will be vaccinated against this serious disease. If you go to your pediatrician to get the Lyme disease vaccine for your children, give up now. It’s simply not available.

Is it because Lyme disease is more serious to your dog than your children? Nope. Is it because Big Pharma makes more money from dogs than humans? No. Is it because the Lyme disease vaccine is safer for a dog than in a human? Not really.

Enough with the guessing game. 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 – anti-vaccine activists. This was in the mid-1990s, and the internet was barely usable without Google to help us, but there were people pushing the same narrative that we hear about the cancer preventing HPV vaccine – the Lyme vaccine was worse than the disease. Let’s take time to look at this story.

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 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.

The initial symptoms of Lyme disease include feverheadachefatiguedepression, and a circular skin rash called erythema migrans (EM). If the Borrelia infection is not treated quickly, later symptoms may involve the joints, heart, and central nervous system. There is generally only one known treatment for the infection–antibiotics including doxycyclineamoxicillin, and cefuroxime. The symptoms usually disappear after antibiotic treatment.

As I’ve written previously, the existence of chronic Lyme disease, a condition which some claim is a consequence of the B. burgdorferi infection somehow continuing after antibiotic therapy manifesting in a set of vague symptoms, is 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. It was given in a three-dose series. 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.

On the other hand, there are three Lyme disease vaccines for dogs – LymeVax, from Fort Dodge Laboratories; Galaxy Lyme, from Intervet-Schering-Plough; and Canine Recombinant Lyme, from Merial. Each work in slightly different ways, with Merial’s vaccine working similar to the human version, where the antibodies attack the bacteria in the tick’s gut. The vaccine isn’t recommended for all dogs, just those in areas with a risk of Lyme disease.

So what happened to the human vaccine?

After the vaccine was introduced in 1998, it sold very well. Because of the fear of Lyme disease, the vaccine also received a lot of positive press, with it being showcased on many morning and evening network news shows (hey, this was 1998, the internet was barely a thing then). However, within a year, the anti-vaccine forces got to work, similar to what we saw with the MMR vaccine causing autism (it doesn’t). Although 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 the controversy surrounding the vaccine.

Between December 28, 1998 and July 31, 2000, nearly 1.5 million doses of the 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, to “prove” certain adverse events. The reports can be made online, by fax or by mail. However, 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, and, frankly, it can be gamed by those with nefarious intentions. VAERS is a feel-good system for those who think that there’s a link between vaccines and something terrible, but without an active investigation by scientists, the data is almost meaningless. The inspirational Orac calls it dumpster diving for data. Even the VAERS system itself says that the data cannot be used to ascertain the difference between coincidence and true causality. There is a background rate for mortality, across all causes, irrespective of whether an individual is vaccinated or not, and unless you understand the background rate, the vaccine “mortality” rate has no scientific meaning. In fact, we could provide a Starbucks coffee drinking in the car “mortality rate”, which may or may not have any causality whatsoever.

Of the 905 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.” Translating their comments, the researchers showed that the VAERS data did not support 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 has not been thoroughly supported by scientific evidence.

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. Nevertheless, it’s clear that the vaccine isn’t recommended for general use, which excludes it from the NVICP program.

In the meantime, Dr. Gregory Poland, a vaccinologist at the prestigious Mayo Clinic and who was a strong advocate for the 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. Physicians effectively treat the majority of these cases with antibiotics, although some cases have complicated courses. Low demand for the vaccine and its subsequent withdrawal from the market represent a loss of a powerful tool for Lyme disease prevention. Although the European vaccine manufacturer Baxter Vaccines has developed a new Lyme vaccine, which they are considering studying in clinical trials, the new vaccine must overcome considerable public aversion for this product to gain widespread global acceptance. As we ask how to weigh public health benefits of interventions against potential risks (notably incurred by identifiable individuals), the LYMErix™ case illustrates that media focus and swings of public opinion can pre-empt the scientific weighing of risks and benefits in determining success or failure.

We’ve seen this story before. The previous version of the pertussis vaccine used whole cell antigens, which may have caused a slightly higher adverse rate but with a higher effectiveness than the current version of the vaccine. And guess who forced this change? Yes, anti-vaccine activists. And now we have outbreaks of pertussis, as the vaccine’s effectiveness wanes over the years.

But things need to change. We 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.

There is some good news. A new multivalent vaccine from Valneva, an Austrian vaccine developer, has entered Phase I clinical trials in the USA. It’s an improvement over the original GlaxoSmithKline vaccine, in that it will work against different Lyme disease subtypes in both the USA and Europe.

I know that vaccine manufacturers have to be cognizant of public perception of their vaccines. But these vaccine companies need to stand up to the nonsense being pushed by anti-vaccine types, who promote unscientific and unsubstantiated narratives about vaccines. Merck stands behind Gardasil, a wonderful vaccine that prevents several types of disfiguring and dangerous cancers, which is constantly being attacked by the anti-vaccine myth makers.

Lyme disease is a dangerous and expensive disease to treat. And 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. Although this won’t be a popular opinion, we need to ignore the misinformation spread by the anti-science crowd, and let humans get the same benefit as dogs – resistance to Lyme disease.

 

Citations

 
 
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!