Optimisation of dose level and vaccination schedule for the VLA15 Lyme borreliosis vaccine candidate among healthy adults: two randomised, observer-blind, placebo-controlled, multicentre, phase 2 studies

• Published in: The Lancet infectious diseases 2024-09, Vol.24 (9), p.1045-1058
• Main Authors: Bézay, Nicole, Wagner, Laura, Kadlecek, Vera, Obersriebnig, Michaela, Wressnigg, Nina, Hochreiter, Romana, Schneider, Martina, Dubischar, Katrin, Derhaschnig, Ulla, Klingler, Anton, Larcher-Senn, Julian, Eder-Lingelbach, Susanne, Bender, Wolfgang
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Adults; Adverse events; Aged; Aluminum; Antibodies; Antibodies, Bacterial - blood; Antigens, Surface - administration & dosage; Antigens, Surface - immunology; Arachnids; Arthritis; Bacterial Outer Membrane Proteins - immunology; Bacterial Vaccines; Belgium; Borrelia burgdorferi - immunology; Borreliosis; Clinical trials; Erythema; Female; Germany; Healthy Volunteers; Human performance; Humans; Immune response; Immunization; Immunization Schedule; Immunoglobulin G; Insect bites; Lipoproteins - administration & dosage; Lipoproteins - immunology; Lyme Disease - prevention & control; Lyme Disease Vaccines - administration & dosage; Lyme Disease Vaccines - immunology; Male; Middle Aged; Monitoring; OspA protein; Outer surface protein A; Placebos; Population studies; Protein A; Randomization; Safety; Schedules; Serotypes; Single-Blind Method; Surface protein A; United States; Vaccination - methods; Vaccines; Young Adult
• ISSN: 1473-3099; 1474-4457; 1474-4457
• DOI: 10.1016/S1473-3099(24)00175-0

Rising Lyme borreliosis incidence rates, potential for severe outcomes, and limitations in accurate and timely diagnosis for treatment initiation suggest the need for a preventive vaccine; however, no vaccine is currently available for human use. We performed two studies in adults to optimise the dose level and vaccination schedule for VLA15, an investigational Lyme borreliosis vaccine targeting outer surface protein A (OspA) serotypes 1–6, which are associated with the most common pathogenic Borrelia species in Europe and North America. Both randomised, observer-blind, placebo-controlled, multicentre phase 2 studies included participants aged 18–65 years without recent history of Lyme borreliosis or tick bites. Study one was conducted at nine clinical research and study centre sites in the USA (n=6), Germany (n=2), and Belgium (n=1); study two was conducted at five of the study one US sites. Based on a randomisation list created by an unmasked statistician for each study, participants were randomly assigned via an electronic case report form randomisation module to receive 90 μg (study one only), 135 μg, or 180 μg VLA15 or placebo by intramuscular injection at months 0, 1, and 2 (study one) or 0, 2, and 6 (study two). Study one began with a run-in phase to confirm safety, after which the Data Safety Monitoring Board recommended the removal of the 90 μg group and continuation of the study. In the study one run-in phase, randomisation was stratified by study site, whereas in the study one main phase and in study two, randomisation was stratified by study site, age group, and baseline B burgdorferi (sensu lato) serostatus. All individuals were masked, other than staff involved in randomisation, vaccine preparation or administration, or safety data monitoring. The primary endpoint for both studies was OspA-specific IgG geometric mean titres (GMTs) at 1 month after the third vaccination and was evaluated in the per-protocol population. Safety endpoints were evaluated in the safety population: all participants who received at least one vaccination. Both studies are registered at ClinicalTrials.gov (study one NCT03769194 and study two NCT03970733) and are completed. For study one, 573 participants were screened and randomly assigned to treatment groups between Dec 21, 2018, and Sept, 26, 2019. For study two, 248 participants were screened and randomly assigned between June 26 and Sept 3, 2019. In study one, 29 participants were assigned to receive 90 μg VLA15, 2