WASHINGTON — An investigational Lyme disease vaccine covering six serotypes across four Borrelia species had a vaccine efficacy (VE) rate of over 70%, but it just missed a preset noninferiority threshold, a placebo-controlled phase III trial showed.
Among participants ages 5 years and older in the evaluable population, four who received four doses of the LB6V vaccine developed Lyme disease compared with 15 participants who received placebo, for a VE rate of 73.2% (95% CI 15.8-93.5), which missed the predefined success threshold in which the lower end of the confidence interval had to be greater than 20%.
However, viewing the numbers through a modified intent-to-treat lens allowed the trial to just clear its success threshold, with a VE rate of 74.8% (95% CI 21.7-93.9), reported Paul Auwaerter, MD, of Johns Hopkins University School of Medicine in Baltimore, at the IDWeek annual meeting.
Despite the statistical miss, “overall, I do think this vaccine has the potential to lower the Lyme disease burden,” Auwaerter said.
Caused by blacklegged tick-borne Borrelia bacterial infection, Lyme disease symptoms include fever, headache, fatigue, and a characteristic bullseye skin rash called erythema migrans. Untreated, the infection can spread to joints, the heart, and the nervous system. In the U.S., more than 80,000 Lyme disease cases are reported to the CDC annually, with an estimated 476,000 people treated every year.
There are no currently available vaccines for Lyme disease. The FDA approved a recombinant vaccine, LYMErix, in 1998, but its manufacturer pulled it from the market in 2002 amid side effect worries and diminishing sales.
LB6V is an adjuvanted, protein subunit vaccine that targets six serotypes of the four most common Borrelia species in Europe and North America. People vaccinated with LB6V pass antibodies to biting ticks infected with Borrelia burgdorferi; those antibodies inhibit the bacteria in ticks and prevent transmission to humans. Formerly known as VLA15, LB6V generated immunogenicity and appeared safe in two phase II trials.
The VALOR trial, conducted in five European countries, Canada, and the U.S., enrolled approximately 9,400 people ages 5 years and up at increased Lyme disease risk 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. The study’s primary efficacy endpoint was vaccine efficacy against Lyme disease from 28 days after the fourth dose through the end of the Lyme disease season.
Adverse events occurred in 58.8% of LB6V recipients compared with 52.6% of placebo recipients — with 0.3% and 0.1%, respectively, having a treatment-related adverse event that prompted patient withdrawal. Newly diagnosed chronic medical conditions occurred in 9.6% of vaccine recipients and 9.5% of placebo recipients.
Fatigue, headache, muscle pain, and joint pain were all more likely in vaccine patients than placebo patients, as were injection-site pain, redness, and swelling.
The VE rate with LB6V fell from 73.2% in the second season after four-dose vaccination 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.
Given that fall-off, LB6V likely isn’t a one-and-done vaccine. “An annual booster before a Lyme disease season would make sense,” Auwaerter said.
He added that the relationship between vaccine efficacy and antibody titers between seasons two and three shows that “these titers are associated with a lower risk of Lyme disease and actually may prove to be a potential basis moving ahead for immunobridging studies.”
