An experimental Lyme disease vaccine showed a 73% efficacy rate in a late-stage trial but did not meet a predefined statistical threshold for success.
The trial, called VALOR, was a placebo-controlled phase III study. Among participants ages 5 and older, four people who received the LB6V vaccine developed Lyme disease. In the placebo group, 15 people developed the illness.
This resulted in a vaccine efficacy (VE) rate of 73.2% (95% CI 15.8-93.5). However, the study required the lower end of the confidence interval to be greater than 20% to declare success. The result missed this mark.
When viewed through a modified intent-to-treat analysis, the trial cleared the threshold. The VE rate was 74.8% (95% CI 21.7-93.9), according to Paul Auwaerter, MD, of Johns Hopkins University School of Medicine, who presented the findings at the IDWeek annual meeting.
Lyme disease is caused by a bacterial infection from blacklegged ticks. Symptoms include fever, headache, fatigue, and a bullseye rash called erythema migrans. If untreated, it can spread to joints, the heart, and the nervous system. The CDC reports over 80,000 cases annually in the U.S., with an estimated 476,000 people treated each year.
There are no currently available vaccines for Lyme disease. The FDA approved a vaccine called LYMErix in 1998, but it was withdrawn from the market in 2002 due to concerns about side effects and low sales.
LB6V is an adjuvanted, protein subunit vaccine that targets six serotypes of the four most common Borrelia species in Europe and North America. The trial enrolled approximately 9,400 people in the U.S., Canada, and five European countries who were at increased risk for Lyme disease through occupation, home environment, or leisure activities. Patients received four doses of the vaccine or placebo at baseline, 2 months, ~5-9 months, and ~18 months. The trial covered three Lyme disease seasons from 2022 to 2025. Median patient age was 47 years, 52% were female, 95.8% were white, and 97% had at least two Lyme disease risk factors.
Adverse events occurred in 58.8% of LB6V recipients compared with 52.6% of placebo recipients. Fatigue, headache, muscle pain, joint pain, and injection-site reactions such as pain, redness, and swelling were more frequent among vaccine recipients. Newly diagnosed chronic medical conditions occurred in 9.6% of vaccine recipients and 9.5% of placebo recipients. Treatment-related adverse events leading to withdrawal occurred in 0.3% of vaccine recipients and 0.1% of placebo recipients.
The vaccine’s efficacy dropped significantly in the third season of the trial. The VE rate fell from 73.2% in the second season to 18.6% in the third season (95% CI -220.0 to 80.4). That drop was mirrored in geometric mean titers of B. burgdorferi anti-outer surface protein A serotype 1 antibodies, which declined from 1,100.3 to 35.7 from season two to season three.