Lyme disease is a bacterial infection transmitted to humans through the bite of infected blacklegged ticks. The condition is caused by Borrelia burgdorferi and related Borrelia species, which are passed from the tick to the host during a blood meal. A vaccine is a preventative measure designed to train the immune system to recognize and neutralize a pathogen, thereby preventing the development of disease. The search for an effective vaccine to combat this common vector-borne illness has a complex history, marked by a brief period of availability and a recent resurgence of development efforts.
The History of the First Human Vaccine
The first and only human Lyme disease vaccine approved for use in the United States, known as LYMErix, was licensed by the Food and Drug Administration (FDA) in December 1998. This vaccine demonstrated an efficacy of approximately 78% in preventing infection after the full three-dose series was administered. It targeted a specific protein on the surface of the Borrelia bacterium and was recommended for people between the ages of 15 and 70 who lived in high-risk areas.
Despite its demonstrated efficacy, the vaccine faced significant challenges almost immediately after its release. Public concern was fueled by media reports and lawsuits alleging a link between the vaccine and the development of chronic arthritis. Although subsequent FDA analysis found no scientific evidence to support a causal relationship between the vaccine and chronic adverse events, the negative publicity persisted.
Sales of the vaccine declined dramatically due to media controversy, lawsuits, and public mistrust toward vaccines. The manufacturer ultimately decided to voluntarily withdraw LYMErix from the market in 2002, citing poor sales performance. This withdrawal was based on commercial viability and public perception, not a failure of the vaccine’s safety or effectiveness.
Understanding the Vaccine Mechanism
The mechanism used by Lyme disease vaccines is distinct from many traditional vaccines that directly target a pathogen inside the human body. These vaccines target Outer Surface Protein A (OspA), a specific molecule highly expressed by the Borrelia bacterium while residing in the midgut of the unfed tick.
When a vaccinated person is bitten by an infected tick, the host’s antibodies are drawn into the tick’s midgut as it feeds on the blood. These OspA-specific antibodies bind to the bacteria, effectively neutralizing them within the tick itself. This unique process, often referred to as “tick-gut immunity,” prevents the bacteria from migrating into the tick’s salivary glands and subsequently into the human host.
The OspA protein is downregulated by the Borrelia bacteria once they leave the tick and enter the mammalian host. Protection is contingent on maintaining a high concentration of circulating antibodies in the human bloodstream, which requires regular booster doses. This reliance on neutralizing the pathogen within the vector is a unique strategy for disease prevention.
Current Status of New Human Vaccine Candidates
Following the withdrawal of the first vaccine, a new generation of human Lyme vaccine candidates is now in advanced stages of development. The most prominent candidate is a multivalent protein subunit vaccine, VLA15, currently being co-developed by Valneva and Pfizer. VLA15 is designed to protect against six of the most common Borrelia serotypes found in North America and Europe, representing an improvement over the previous monovalent vaccine.
The vaccine is currently being evaluated in a large-scale Phase 3 clinical trial. This trial, named Vaccine Against Lyme for Outdoor Recreationists (VALOR), is investigating the safety, immunogenicity, and efficacy in participants five years of age and older. Enrollment has been completed, with participants being monitored for the occurrence of Lyme disease cases.
Subject to positive Phase 3 data, the manufacturers aim to submit a Biologics License Application to the FDA and a Marketing Authorization Application to the European Medicines Agency in 2026. If the regulatory process moves forward, the vaccine could potentially become commercially available to the public in the second half of 2027.
Canine Lyme Disease Vaccines
While a human vaccine is not currently available, vaccines for the prevention of Lyme disease in dogs have been widely used for many years. These veterinary products are considered a non-core vaccine, meaning they are recommended based on a dog’s risk of exposure in endemic areas. The availability of these products often contributes to public confusion regarding the status of a human vaccine.
Canine vaccines also utilize the OspA protein, inducing an immune response that works through the same tick-gut immunity mechanism as the human candidates. The antibodies are ingested by a feeding tick and kill the Borrelia bacteria before they can be transmitted to the dog. Some canine vaccines also include Outer Surface Protein C (OspC) to provide a broader protective response.
These established canine vaccines are specifically formulated and approved for veterinary use only. They are not interchangeable with or a substitute for any human-approved vaccine candidate. The continued development of these animal vaccines underscores the importance of this preventative strategy in managing the disease burden in high-risk areas.