Lessons Unlearned: The Barriers to Lyme Borreliosis Vaccination and the Risk of Repeating History

Lyme borreliosis is the most common vector-borne disease in the temperate Northern Hemisphere, with approximately 476,000 diagnoses annually in the United States and over 130,000 reported cases across Europe each year, figures that substantially underestimate true incidence. In 1998, LYMErix became the first licensed vaccine against Lyme borreliosis. Its withdrawal four years later was not driven by evidence of vaccine failure but by the collapse of public confidence, and regulatory endorsement that any successful vaccine programme requires. The field was without a licensed product for twenty-four years. VLA15 (now designated PF-07307405), a second-generation recombinant outer surface protein A vaccine, is now at regulatory submission following phase 3 results reported in March 2026. We examine the barriers that led to LYMErix’s withdrawal, revisit the evidence that generated and sustained the safety controversy and consider whether the conditions now exist for a different outcome. The lessons for a robust post-marketing surveillance programme extend beyond Lyme borreliosis to broader questions about how modern medicine evaluates vaccine risk, interprets safety signals, and communicates under uncertainty.