May is National Lyme Disease Awareness Month, timed to coincide with the emergence of ticks with warmer spring weather. A record number of ticks that transmit several infectious diseases are expected in Connecticut this year, including babesiosis, anaplasmosis and others. The Agricultural Experiment Station in New Haven tracks ticks and is already recording about 40 % more than the same period last year, another consequence of global warming.

Pandemic weary Connecticut residents with cabin fever, many fully Covid-vaccinated, are venturing out to tick habitats in backyards, woods, and other environments where roam the white-tailed deer and white-footed mice that host the ticks. None of these folks are vaccinated against Lyme disease, though many of their dogs are.

Why not humans?

A safe and effective licensed FDA approved vaccine against Lyme infection exists that was voluntarily withdrawn from the market in 2002 by its manufacturer, citing a precipitous drop in sales caused by anti-vaccine campaigns, negative media coverage, and unfounded safety concerns.

Lyme disease is the most common vector borne disease in North America and Europe.

Using various surveillance methods that consider underreporting and insurance data, the Centers for Disease Control and Prevention predicts almost half a million Americans will be diagnosed and treated this year. Caused by a corkscrew-shaped bacterium transmitted to humans by the black legged or deer ticks, most infected individuals do not notice the bite. Tick saliva contains an anesthetic that helps conceal its presence while feeding on the victim’s blood before dropping off.

Infection can be asymptomatic or, days to weeks later, cause a characteristic rash, headache, fever, chills, joint or muscle aches. The flu-like illness of early Lyme infection shares many symptoms with other diseases and thus may be difficult to diagnose. If not treated early, it can spread to the nervous system, heart and joints, causing late-stage disease that resists treatment. Early symptoms may be absent or missed and Bell’s palsy, meningitis, heart-rhythm disturbances and arthritis are frequent initial presentations. A chronic Lyme syndrome, possibly an autoimmune reaction that has been compared to “long-haul Covid,” has been identified and also defies easy remedy.

Vaccine comes and goes

Long-time residents of southeastern Connecticut may remember the much-publicized national Lyme vaccine trial that tested the safety and efficacy of LYMErix, developed by SmithKline Beecham (now GlaxoSmithKline) in the late 1990s. As principal investigator of that study, I enrolled 1,200 adults and 800 children as young as four-years-old from New London County to receive vaccine or placebo. With the public increasingly aware and concerned about difficulties with Lyme diagnosis and treatment, more enthusiastic volunteers turned up for shots than we could accommodate.

About 11,000 adults and 4,000 children took part at study sites in Lyme endemic states across the country in two late-stage trials. Study participants were at high risk of contracting Lyme disease due to their residence in those areas, recreational activities or occupational exposure. We tested them regularly and followed them closely for symptoms of Lyme disease and possible vaccine side effects through two tick transmission seasons over two years.

The vaccine’s effectiveness in preventing infection in adults was about 80%, and 100% effective against asymptomatic cases. The pediatric study, conducted after safety and efficacy were proved in adults, showed superior antibody responses and no safety issues.

It worked.

We published clinical trial data in “The New England Journal of Medicine” in July 1998 followed by unanimous support for licensure by an FDA advisory panel and full approval six months later. More than 1.5 million people were given the vaccine over the next two years, effectively preventing infections at a level comparable to other commonly used vaccines.

So, what happened?

A number of adverse factors converged to doom its success. First, the Advisory Committee on Immunization Practices gave the vaccine a lukewarm “permissive recommendation,” a designation that omitted it from childhood and adult immunization schedules, instead endorsing it for use only in individuals with specific risk factors for the disease. The guidance was confusing for both patients and doctors, whom the manufacturer bypassed by marketing the vaccine directly to the public without first adequately educating them about its use. Most insurance companies do not pay for vaccines with this status and the cost of about $50 per dose for three shots was a significant deterrent for many people.

Concerns were raised about the possibility of the vaccine causing a form of autoimmune arthritis in genetically susceptible individuals. Questions snowballed. How long would the protection last? Would booster doses be needed? Safety and dosing data for children younger than 15, amongst the groups at highest risk for infection, was not yet available.

A less well-known factor that helped set the stage for a perfect storm that doomed LYMErix was the publication in February of 1998 of a case report in the respected British medical journal “The Lancet” of 12 children that linked their autism to receipt of the MMR vaccine. MMR is an eminently safe and effective vaccine administered to hundreds of millions of children every year around the world to prevent potentially devastating infection with measles, mumps and rubella viruses. Based on junk science and written by a physician who was later stripped of his medical license, the paper was eventually retracted by the journal but not before the damage was done.

Many public health experts date the birth of the current anti-vaccine movement to that treacherous article in “The Lancet” that has resulted in more public health harm than any other publication in modern times. Outbreaks of measles have occurred throughout the world. Vaccine skepticism and refusal have extended to all vaccines. The LYMErix safety and efficacy data were published in “The New England Journal of Medicine” just six months after that fraudulent report deceptively linking autism to MMR vaccine. The newly approved Lyme vaccine was launched at the end of the same year. The timing could not have been worse.

The public is generally unaware that there is a National Vaccine Injury Compensation Program. Created in 1988, it provides compensation to individuals deemed to have been harmed by vaccines specifically listed in the Advisory Committee on Immunization Practices’ recommended vaccine schedule. A federal claims court rules on the merits of claims, effectively eliminating frivolous lawsuits while protecting both manufacturers and individuals. LYMErix was not listed or covered in the recommended schedule. Thus individuals were free to file lawsuits directly against SmithKline Beecham and these mushroomed along with a burgeoning list of alleged vaccine side effects.

National news media seized the opportunity for the public’s attention with sensational headlines and prime-time reports of Lyme vaccine complications without any objective evidence. Then, as now, anti-vaccine groups were far more active and vociferous than the scientific community. Widespread confusion amongst the public, prescribing physicians and medical societies led to another meeting of the FDA vaccine advisory panel in 2001 to analyze safety data that was available after about 1.5 million Americans had received the vaccine. The FDA review concluded that there was no evidence to support the alleged safety concerns and that any theoretical risks were outweighed by the benefits.

By this time, acceptance of the vaccine rapidly declined. Finally, faced with class-action lawsuits and unrelenting negative media coverage, SmithKline Beecham discontinued the vaccine four years after its approval. With that executive decision in a corporate suite, a safe and effective shield to help prevent Lyme disease was removed, indecorously concluding an unprecedented public health debacle.

During the ensuing two decades, personal protective measures to prevent tick bites and environmental programs to control tick and deer populations have been ineffective as case numbers have continued to increase progressively. Periodic efforts to revive LYMErix or develop a new vaccine in the United States have fizzled out with manufacturers wary of repeating the fiasco.

A new vaccine?

So what about the future? With dramatic increases in Lyme disease infections in North America and Europe, the need and demand for a Lyme vaccine is greater than before. Memories of the LYMErix experience have faded. Valneva, a small biotech company in France that focuses on vaccines for infectious diseases with unmet needs, has spent the past seven years developing a vaccine that prevents infection with all six common strains of the Lyme bacterium found in the northern hemisphere. Though it works similarly to LYMErix, which protected only against the single strain found in the U.S. and Canada, the manufacturer also re-engineered it to eliminate and replace the molecular segment that theoretically caused autoimmune arthritis.

Valneva’s candidate Lyme vaccine received fast-track designation from the FDA in 2017. Having successfully completed Phase 1 and 2 trials, it needed a major pharmaceutical company to help conduct the large late-stage Phase 3 studies required to demonstrate its efficacy and bring it to market.

Following in the footsteps of BioNTech, the small German biotech company that developed a version of Covid-19 mRNA vaccine and partnered successfully with Pfizer, Valneva also announced in 2020 a collaboration with Pfizer. Over the next couple of years, they are planning to conduct large-scale final trials in the U.S. and Europe. If successful, they could apply for approval in three or four years.

The BioNTech COVID vaccine is now well known as the Pfizer COVID vaccine. Perhaps, by the middle of this decade, we will have a Pfizer Lyme vaccine. At present it is known simply as VLA15.

The burning question, with no easy answer, is whether a new Lyme vaccine that is safe and highly effective will be widely accepted.

On the one hand, there are reports of people so worried about Lyme disease that they are approaching veterinarians to ask about the possibility of using the canine vaccine for themselves.

On the other hand, anti-vaccination groups are swamping cyberspace with misinformation and disinformation. If they can dominate and damage the COVID vaccine debate, what can we expect for a reincarnated Lyme shot?

Political and cultural influences are notorious adversaries of science. We need more sophisticated educational tools to outflank World Wide Web trolls and reverse senseless ignorance of the enormous public health benefits of vaccines.

Dr. Vijay K Sikand works in the Departments of Medicine and Pediatrics for Yale New Haven Health at Lawrence + Memorial Hospital, New London. He is an adjunct assistant professor of medicine for the Tufts University School of Medicine. He co-authored the medical textbook, “Lyme Borreliosis in Europe and North America/Epidemiology and Clinical Practice.”