Ghadge et al. Immunogenicity and safety of an 18-month booster dose of the VLA15 Lyme borreliosis vaccine candidate after primary immunisation in healthy adults in the USA: results of the booster phase of a randomised, controlled, phase 2 trial. Lancet Infect Dis. 2024;24(11):1275-1286. doi:10.1016/S1473-3099(24)00372-4
Lyme disease, caused by Borrelia burgdorferi sensu lato, affects over 470,000 people annually in the United States and more than 130,000 in Europe. Severe manifestations, such as Lyme carditis, Lyme neuroborreliosis, or Lyme arthritis, occur in 10–30% of patients. Additionally, 5–10% of patients experience persistent symptoms despite antibiotic treatment. Currently, no vaccine is available to prevent Lyme disease in humans.
A hexavalent Lyme disease vaccine candidate has been developed, targeting six OspA serotypes (1, 2, 3, 4, 5, and 6) of the outer membrane protein. The vaccine comprises two fusion proteins, each incorporating three different OspA serotypes. These antigens are estimated to cover over 97% of Borrelia species (B. burgdorferi ss, B. afzelii, B. bavariensis, B. garinii, and B. spielmanii) prevalent in the US and Europe.
Various antigen concentrations and immunization schedules have been evaluated. For phase 2 studies, a regimen of three injections—administered at months 0, 2, and 6—was tested, with each dose containing 180 µg of the vaccine.
Phase 2 clinical trials demonstrated that the vaccine was safe, well-tolerated, and capable of eliciting strong anti-OspA immune responses in both adult and pediatric volunteers. Across all age groups, the most common local adverse reactions were tenderness and pain, while systemic adverse reactions included muscle pain, headache, and fatigue.
The highest geometric mean titers (GMTs) were observed in vaccine recipients aged 5–11 years, followed by the 12–17-year and 18–65-year age groups. A booster dose administered one year after the initial three-dose series significantly increased OspA-specific IgG GMT titers across all age groups.
A phase 3, multicenter, placebo-controlled, randomized, observer-blinded trial has been initiated to evaluate the efficacy of the hexavalent Lyme disease vaccine. The primary endpoint is vaccine efficacy following the fourth dose. The study involves participation over a duration of up to 30 months, with a subset of participants monitored for an additional 12 months. Participants enrolled in 2023 underwent their first season of Lyme disease surveillance in 2024. Those enrolled in 2022 completed the fourth dose in June 2024 and underwent a second season of Lyme disease surveillance the same year.
A second booster dose, administered one year after the initial booster, elicited significant antibody responses across all six serotypes in children, adolescents, and adults, with seroconversion rates exceeding 90% for all OspA serotypes. The requirement for periodic boosters is yet to be determined.
Valneva, in partnership with Pfizer, plans to launch the vaccine in 2027.
Further insights into this six-serotype vaccine and other Lyme disease vaccines in development are detailed in the article by Plotkin and Shapiro, The Current and Future State of Vaccines for Lyme Disease, Clinical Infectious Diseases (2024, in press, DOI: 10.1093/cid/ciae647).