Lyme disease is the most common vector-borne illness in the United States.1 The U.S. Centers for Disease Control and Prevention (CDC) says that state health departments reported over 63,000 cases in 2022.2 However, the CDC uses other methods to estimate that approximately 476,000 people in the U.S. may be diagnosed and treated for Lyme disease annually.2

In other words, the estimated number of Lyme disease cases in the U.S. seems to be much higher than what is being reported to public health officials.3

“The prevalence of this disease remains high, despite a growing awareness,” Raphael Simon, PhD, Senior Director of Vaccines Research and Development at Pfizer, says. “In areas where this disease is endemic (constantly present), up to half of surveyed ticks can carry the Borrelia bacteria," he says.

Understanding the Risks

In the United States, Lyme disease is primarily caused by the spiral-shaped bacterium Borrelia burgdoferi and is spread through a bite from an infected Ixodes scapularis tick.4 A rash called erythema migrans occurs in 70-80% of infected people and can present with different characteristics.5 Other early symptoms such as headache, fever, and fatigue, may occur with or without a rash.5 Untreated Lyme disease can produce a wide range of symptoms, including late-stage manifestations involving neurological or cardiovascular systems or arthritis.5,6

Each encounter with an infected tick may carry a risk of developing Lyme disease.7 While antibiotics like doxycycline is one of the recommended treatment options, there is a growing need for effective preventative measures.8,9 A review of individual protective measures found limited evidence of their effectiveness at preventing Lyme disease.10 These measures, recommended by the Centers for Disease Control and Prevention, included tick checks, protective clothing, and repellant use.11 
Research published in BMC Infectious Diseases showed that a single dose of prophylactic antibiotics following a tick bite decreased the likelihood of developing Lyme disease following a tick bite compared to placebo.12 However, early diagnosis and treatment is crucial as it can help prevent severe disease.13

The Lyme Disease Footprint is Expanding

The uptick in cases may also be linked to an expanded geographic range for ticks. Changes to land use patterns, such as suburban development, have led to a greater number of encounters between people and ticks.14,15 Climate change may also play a role.15

“Ticks require a certain type of environment at the right temperature and right humidity in order to thrive and that can change as the climate changes,” Dr. Simon explains.

With both the prevalence and geographic range of Lyme disease increasing, vaccination could help prevent the disease and ease its burden.15

Hope on the Horizon—A Human Vaccine Candidate for Lyme Disease

In 2020, Pfizer announced a collaboration with Valneva, a European company specializing in vaccines, to codevelop and commercialize a vaccine candidate against Lyme disease.16 The investigational product, VLA15, is a multivalent protein subunit vaccine that targets the outer surface protein A (OspA) expressed by the Borrelia bacteria when it is inside the tick.16

The vaccine has a unique mechanism, according to Dr. Simon. It works inside the gut of the tick. Once vaccinated, the recipient generates antibodies against the OspA protein and, after receiving a tick bite, the antibodies go into the feeding tick along with the blood meal and neutralize the Borrelia bacteria, preventing it from being transmitted to the host and causing Lyme disease, he says.

A single type of Borrelia causes most of the Lyme disease in the U.S.; however, in Europe, there is a broader range of variants (which includes the U.S. species).17 VLA15 has been designed to offer coverage for the most common circulating types of Borrelia bacteria that cause Lyme disease in both regions.18

In Phase 2 clinical trials, results showed that VLA15 was safe and well-tolerated, and generated strong anti-OspA immune responses in adults and pediatric volunteers.18 A Phase 3 clinical study, Vaccine Against Lyme for Outdoor Recreationists (VALOR) (NCT05477524), investigating the efficacy, safety and immunogenicity of VLA15 was initiated in August 2022.19 Subject to positive data, Pfizer plans to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) and Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in 2026.20 As of September 2024, VLA15 has advanced furthest in clinical development of any active Lyme vaccine candidate.20

Preclinical experiments in animal models found that the vaccine candidate was able to induce a broad protective immune response targeting the majority of Lyme disease-causing spirochetes in Europe and the US.18, 21 If it is found to be similarly successful in people, Dr. Simon says, it could provide an important tool to reduce the disease burden resulting from the expanding geographic distribution of ticks and increasing cases of Lyme disease.