Lyme disease is a bacterial infection transmitted to humans through the bite of infected blacklegged ticks. This illness, caused by Borrelia burgdorferi, is a public health concern, especially in the Northeast, Mid-Atlantic, and Upper-Midwest United States. Symptoms can include fever, headache, fatigue, and a distinctive expanding skin rash known as erythema migrans. Untreated infections can spread to joints, the heart, and the nervous system, leading to severe complications. With an estimated 476,000 people diagnosed and treated for Lyme disease annually in the United States, the development of effective preventive measures, including vaccines, remains a focus.
The Discontinued Human Lyme Vaccine
LYMErix, developed by SmithKline Beecham (later GlaxoSmithKline), was a human Lyme disease vaccine. It received approval from the U.S. Food and Drug Administration (FDA) in December 1998. LYMErix was designed to protect individuals aged 15 to 70 years, particularly those living or working in areas with high rates of Lyme disease.
Clinical trials demonstrated the vaccine was effective, showing approximately 78% efficacy in preventing Lyme disease after three doses. Despite its effectiveness, LYMErix was voluntarily withdrawn from the market by its manufacturer in 2002. This decision was not due to an FDA recall for safety concerns, but rather a combination of other factors.
Public demand for the vaccine was lower than anticipated, partly influenced by negative media coverage. The manufacturer also faced class-action lawsuits alleging a link between the vaccine and arthritis. Although the FDA investigated these claims and found insufficient scientific evidence to support a causal relationship, public perception was significantly impacted. Skepticism towards new vaccines at the time also contributed to its limited acceptance and discontinuation.
Current Vaccine Candidates in Development
The most advanced Lyme disease vaccine candidate in human clinical development is VLA15, co-developed by Pfizer and Valneva. This vaccine is currently undergoing Phase 3 clinical trials to confirm its efficacy, safety, and immunogenicity. The primary Phase 3 study, named VALOR (Vaccine Against Lyme for Outdoor Recreationists), began in August 2022 and has completed participant recruitment.
The VALOR trial enrolled 9,437 participants aged five years and older across Lyme disease-endemic regions in the U.S., Europe, and Canada. Participants receive a primary series of three doses of VLA15 or a placebo, followed by a booster dose approximately one year later. A second Phase 3 trial, focusing on VLA15’s safety profile in pediatric populations, is also ongoing and has completed enrollment.
VLA15 is a multivalent protein subunit vaccine engineered to target six different serotypes of the Borrelia burgdorferi sensu lato species. These serotypes are the most common strains responsible for Lyme disease in North America and Europe. The VALOR trial is anticipated to conclude by the end of 2025. Pfizer aims to submit regulatory filings to both the U.S. Food and Drug Administration and the European Medicines Agency in 2026, assuming positive trial results.
The Unique Mechanism of Lyme Disease Vaccines
Lyme disease vaccines, particularly those based on the outer surface protein A (OspA), employ a distinct mechanism of action. These vaccines stimulate the human body to produce antibodies specifically against OspA, a protein found on the surface of Borrelia bacteria. OspA is abundantly expressed when the bacteria reside within the gut of unfed ticks.
When an infected tick bites a vaccinated person, it ingests these circulating anti-OspA antibodies with the blood meal. Inside the tick’s midgut, the ingested antibodies bind to the OspA protein on the Borrelia bacteria. This binding neutralizes the bacteria and prevents them from migrating from the tick’s gut to its salivary glands, a necessary step for transmission to the human host.
Effectively, the vaccine works by eliminating the bacteria within the tick itself before transmission to the human. This “transmission-blocking” approach protects the vaccinated individual because the pathogen is stopped in the vector, rather than after it has entered the human body. This strategy relies on maintaining high titers of circulating antibodies in the vaccinated person’s bloodstream.
Future Accessibility and Public Perception
The potential approval of a new Lyme disease vaccine would introduce several practical and societal considerations. A new vaccine would likely be aimed at individuals with higher exposure risk, such as those residing in Lyme disease-prevalent areas, outdoor workers, and children who frequently engage in outdoor activities. These groups represent the populations that could benefit most from an additional preventive measure.
A challenge for any new Lyme vaccine will be overcoming public hesitancy, which lingers from the controversy surrounding the previous LYMErix vaccine. Despite scientific findings that did not support serious safety concerns, past negative media and legal issues created a lasting public perception. Effective public health communication strategies will be necessary to rebuild trust and inform the public about the safety and benefits of a new vaccine.
Such strategies would need to address past concerns directly, emphasize the scientific rigor of new trials, and highlight the burden of Lyme disease. Studies indicate that both consumers and clinicians in high-incidence areas express support for a new vaccine, driven by concerns about disease diagnosis and treatment challenges, and the need for effective prevention. Clear communication regarding the vaccine’s benefits and the lack of existing highly effective preventive measures could facilitate its acceptance and uptake.