Pfizer, Valneva report promising results in Lyme vaccine trials

A new Lyme disease vaccine candidate developed by Pfizer and Valneva has posted promising clinical trial results, raising hopes that the first widely available human Lyme vaccine in more than two decades could soon return to the market.  

In March, the companies released the results of a Phase 3 clinical trial for their vaccine candidate, known as LB6V. The vaccine demonstrated efficacy rates above 70 percent in preventing Lyme disease among trial participants age 5 and older, and researchers also reported that the vaccine was generally well tolerated and no major safety concerns had emerged.  

The findings come at a welcoming time for health officials because Lyme disease continues to expand its footprint across the United States and Europe. The CDC says approximately 476,000 Americans are diagnosed and treated for Lyme disease each year, while roughly 132,000 cases are reported annually in Europe in countries with surveillance systems.  

People living in Lyme-prone areas acquire Lyme disease from the bite of an infected tick. Early diagnosis and treatment boost outcomes, especially with oral antibiotics. However, some patients develop more serious disease, sometimes suffering chronic neurological, cardiac, or arthritic conditions. Lyme disease is caused by Borrelia bacteria transmitted through infected Ixodes ticks, commonly known as deer ticks or black-legged ticks. 

Early symptoms can include fatigue, fever, headaches, muscle aches, joint pain, and the characteristic expanding “bull’s-eye” rash known as erythema migrans. Left untreated, the disease can progress into more serious complications affecting the nervous system, joints, heart, and skin.  

The disease has become particularly associated with wooded and outdoor recreation regions in the Upper Midwest and Northeast, including Wisconsin, where public health officials routinely warn residents about tick exposure during spring and summer months.

Phase 3 trial results

According to Pfizer and Valneva, the Phase 3 VALOR trial — short for “Vaccine Against Lyme for Outdoor Recreationists” — showed efficacy of 73.2 percent from 28 days post dose 4 in reducing the rate of confirmed Lyme Disease cases compared to a placebo group and efficacy of 74.8 percent from one day post dose 4.  

The multinational trial involved participants in the United States, Canada, and Europe and focused on regions with high Lyme disease incidence. Participants were randomly assigned to receive either the vaccine candidate or a saline placebo.  

Researchers acknowledged that fewer Lyme disease cases accrued over the study period than expected, and the trial did not fully satisfy one of its pre-specified statistical benchmarks. However, the companies said the overall efficacy results remained “clinically meaningful” and announced plans to pursue regulatory submissions.  

“Lyme disease can cause potentially serious consequences — where individuals and families face symptoms that can disrupt daily life, work, and long-term health — and there is currently no vaccine available,” said Annaliesa Anderson, senior vice president and chief vaccines officer at Pfizer. “The efficacy shown in the VALOR study of more than 70 percent is highly encouraging and creates confidence in the vaccine’s potential to protect against this disease that can be debilitating.”  

Thomas Lingelbach, CEO of Valneva, said the results moved the companies a step closer to the goal of delivering a much-needed vaccine to help protect against Lyme disease.

Unlike many vaccines that directly prevent infection inside the human body, this Lyme vaccine candidate works in a completely opposite way. Rather, the vaccine stimulates the human immune system to create antibodies against multiple strains of Borrelia bacteria. When a tick feeds on a vaccinated person, those antibodies enter the tick during the blood meal and attack the bacteria inside the tick before transmission occurs.  

Pfizer and Valneva say the vaccine targets the six most prevalent Borrelia serotypes found across North America and Europe. The vaccine regimen used in the trial involved four doses administered over a year, with the final dose given shortly before the next Lyme season.  

Currently, there is no approved human vaccine for Lyme disease in the United States. The federal Centers for Disease Control and Prevention notes that protection from the only other previously marketed Lyme vaccine in the United States diminished over time, meaning anyone vaccinated before 2002 is no longer protected.  

The CDC said it is monitoring the ongoing clinical trials and researching public attitudes toward any future Lyme vaccine. If approved by the U.S. Food and Drug Administration, the agency said it would work with the Advisory Committee on Immunization Practices to determine recommendations on who should receive the vaccine and in what regions.  

A checkered past

As mentioned, there has been only one previous Lyme vaccine, LYMErix, approved in 1998 but withdrawn from the market only a few years later amid falling sales, public controversy over reported side effects, and lawsuits alleging vaccine-related injuries.  

LYMErix received FDA approval in December 1998 after clinical trials showed approximately 76 percent effectiveness in preventing Lyme disease among vaccinated adults. But within a few years, the vaccine became engulfed in controversy.

In “The Lyme vaccine: a cautionary tale,” in 2006, L. E. Nigrovic and colleague K. M. Thompson of Children’s Hospital in Boston reviewed the history of that vaccine, in which concerns emerged over reports of arthritis and other musculoskeletal symptoms among some vaccine recipients. Media coverage amplified the claims, a class-action lawsuit followed, and public confidence rapidly deteriorated, Nigrovic and Thompson wrote.

According to their paper, published in Cambridge’s Epidemiology and Infection, several manufacturers conducted clinical trials in a race to gain the first license for their vaccine.

“In the LYMErix phase III safety and efficacy trial, researchers enrolled 10,906 subjects between 15 and 70 years old who lived in endemic areas and randomized them to receive either the three-dose Lyme vaccine regimen or placebo injections,” the review stated. “Vaccinated individuals showed a 76 percent reduction in Lyme disease in the year following vaccination, with no significant side-effects noted.”

Based on those findings, the researchers wrote, the U.S. Food and Drug Administration (FDA) approved LYMErix in December 1998. The competitor manufacturer, for reasons that are unknown, did not apply to the FDA for licensure.

“The available Lyme vaccine came with several immediately apparent limitations,” the review stated. “First, the vaccine efficacy of <80 percent meant that 20 percent of fully vaccinated individuals could still get Lyme disease. Second, achieving full protection required three vaccine doses given at the time of the initial dose and 1 month and 12 months after the initial dose.”

Third, the researchers continued, the vaccine safety and efficacy database lacked tests in young children, a population at high risk of developing Lyme disease. 

“Also the vaccine was effective only against the predominant North American Borrelia strain without necessarily conferring protection against international subspecies,” the review stated. “Finally, uncertainty about the length of vaccine-induced immunity implied that recipients might need booster vaccine doses as often as every year to prevent waning immunity.”

What’s more, within a year of licensure, reports of adverse reactions occurring after vaccination started to appear. 

“Although individuals claimed a wide variety of vaccine side-effects, musculoskeletal complaints such as arthritis dominated,” the review stated. “The media put a human face on this suffering by carrying the stories of these ‘vaccine victims.’ The Lyme Disease Network, a non-profit citizen action group, devoted extensive website coverage to this growing controversy.”

The Philadelphia law firm of Sheller, Ludwig & Bailey filed a class action lawsuit against the LYMErix manufacturer, SmithKlineBeecham, in 1999, the researchers wrote. 

“The law firm represented 121 individuals who claimed they experienced significant adverse reactions to the licensed Lyme vaccine,” they wrote. “The suit claimed that the vaccine caused harm and that the manufacturer concealed evidence about its potential risks.”

However, the researchers pointed out, federal reviews at the time found no conclusive evidence that LYMErix caused widespread harm: “Vaccine safety surveillance data showed arthritis rates among vaccine recipients appeared similar to background rates in the general population.”  

In addition, while the company settled the lawsuit and paid more than $1 million in legal fees, it admitted no guilt and paid no compensation to the plaintiffs. Still, the researchers wrote, public confidence eroded.

“Growing public concerns about vaccine safety forced the FDA to re-examine the adverse reactions reported after Lyme vaccine,” the review stated. “The FDA re-examined the published phase III trial that allowed licensing of the vaccine. Significantly more vaccine recipients than controls (i.e. 26.8 percent vs. 8.3 percent) experienced local reactions, including soreness, redness, or swelling at the injection site as well as systemic symptoms such as myalgias, fever, or chills (i.e. 19.4 percent vs.15.1 percent). These symptoms, seen with virtually all immunizations, occurred within 48 h[ours] of injection and lasted a median of 3 days.”

All symptoms resolved without treatment and no difference appeared in the frequency of long-term joint symptoms between the vaccine and the placebo groups, the review stated. 

“However, the trial followed the patients for only 1 year after LYMErix vaccination,” the researchers wrote. “This reassuring side-effect profile allowed vaccine licensure, but left open key questions about long-term effects.”

The bottom line was, the researchers pointed out, in the media and in the minds of much of the public, temporal association became equated with causation. 

“In contrast, the benefits of the vaccine from avoiding the effects of Lyme disease did not get the same kind of coverage,” the researchers wrote. “This suggests that physicians may need to play a more active role in communicating the benefits of vaccines to patients and the mainstream media, in particular by providing important contexts that will help put the anecdotal stories in perspective and by offering examples of stories of people whose lives were saved or improved due to the vaccine.”

To make matters worse, the researchers wrote, the controversy unfolded during a period of heightened national sensitivity regarding vaccine safety following the withdrawal of another vaccine, RotaShield, from the market over rare complications.  

“After nearly a decade in clinical trials, RotaShield entered the market in August 1998 with the promise of dramatically reducing the burden of disease from rotavirus, the most important cause of childhood infectious diarrhea worldwide,” the researchers wrote. “Several months later both the American Academy of Pediatrics (AAP) and ACIP added the RotaShield vaccine to the routine immunization schedule for all infants.”

But with the increase in use, the review stated, the national vaccine adverse events reporting system (VAERS) quickly began receiving rare reports of intussusception, a potentially life-threatening intestinal blockage, and subsequent large case-control and population studies confirmed the association. 

“Epidemiological studies suggested that intussusception occurred in 1–2/10,000 vaccinees, and most experts agreed that this potentially life-threatening risk outweighed the protection against childhood diarrhea,” the researchers wrote. “Consequently in October 1999, 14 months after licensure, the manufacturer withdrew the vaccine.”

More to come?

The Pfizer-Valneva vaccine is not the only Lyme prevention strategy currently under development.

According to the CDC, the University of Massachusetts Medical School’s MassBiologics developed a human monoclonal antibody intended for pre-exposure prophylaxis (PrEP) against Lyme disease. 

“In 2025, MassBiologics licensed the technology to Tonix Pharmaceuticals, which is planning human clinical studies,” the CDC states, adding that the approach would provide seasonal protection against Lyme disease and would likely consist of a single shot that people would get each year before exposure to ticks.

CDC also says it is conducting research to better understand what concerns healthcare providers and the public may have about any potential Lyme disease vaccine. 

“If a Lyme disease vaccine is approved as safe and effective by the Food and Drug Administration (FDA), CDC will work with the Advisory Committee on Immunization Practices (ACIP) to develop recommendations about who and where in the U.S. the public might benefit from a Lyme disease vaccine,” the CDC states. “CDC will communicate these recommendations to the public and healthcare providers.”

Lyme transmission generally requires prolonged tick attachment, meaning early tick removal can significantly reduce infection risk. Protective clothing and insect repellents containing DEET can reduce risk, as can removing underbrush.

Richard Moore is the author of “Dark State” and may be reached at richardd3d.substack.com.