While no treatment currently exists that can remedy post-treatment Lyme disease syndrome, preventative vaccinations for B. burgdorferi are close to entering the market. Phase 3 clinical trials began in 2022 for a preventative vaccination known as VLA15, the only Lyme disease vaccine currently in clinical development (13). This vaccine targets the six most common serotypes of outer surface protein A (OspA) of Borrelia burgdorferi, which will prevent the bacteria from being passed to humans from ticks. However, while pre-clinical and clinical studies have demonstrated a strong immune response and a satisfactory safety profile, it is important to consider that the serotypes chosen for this vaccine are most prevalent within Europe and the United States, therefore limiting its worldwide application (13).
A previously available Lyme disease vaccine, known as LYMErix™, was approved by the FDA in 1998. While preclinical and clinical results were promising, a few limitations arose immediately following its approval. Firstly, with a vaccine efficacy of <80%, 20% of vaccinated individuals were still at risk for developing Lyme disease. Additionally, three vaccine doses were required to achieve full protection, with the potential requirement for additional booster vaccinations as often as every year to maintain full immunity. Thirdly, as the clinical trials only evaluated efficacy in people 15 to 70 years of age, its effectiveness in children was uncertain, and this is notable as they are at high risk for Lyme disease. While these initial apprehensions could be addressed with further clinical studies to refine the vaccine, the time it was brought to market was less than ideal as concerns about other childhood vaccines like the mumps, measles, and rubella (MMR) were on the rise.
As initial promotions of the vaccine emphasized the benefits and did not discuss the potential risks, reports of adverse reactions after vaccination began circulating with media outlets putting a human face and story to these side effects. A non-profit citizen action group, known as The Lyme Disease Network, devoted extensive efforts to cover this growing controversy. Side effects varied widely, but frequently mentioned were musculoskeletal complaints such as arthritis, common vaccine side effects such as swelling at the injection site, and systemic symptoms such as myalgias, fever, or chills. The development of autoimmune arthritis appeared to be linked to patients with a specific human leukocyte associated antigen (HLA) type known as the DR4+ genotype. While a study reported that 4 male patients with the DR4+ genotype developed autoimmune arthritis after receiving the LYMErix™ vaccine, the FDA found no association between autoimmune arthritis and the vaccine in question (14).
Between the conflicting scientific literature, pending lawsuits, and questions from the public and media, the FDA reconvened its advisory panel to determine the future of the LYMErix™ vaccine. The panel, described by one participant as raucous and riotous, consisted of FDA scientific advisors, the LYMErix™ manufacturers, independent experts, practicing physicians, as well as the individuals experiencing adverse vaccine effects and their lawyers. Although the physicians demonstrated how the vaccine enabled dramatic reductions in Lyme disease cases, and scientists suggested the potential role of genetic susceptibility and OspA-related autoimmunity, it was clear that the vaccine was contentious, even if it did benefit a wide majority of patients. The panel concluded that the benefits of the LYMErix™ vaccine continued to outweigh its risks, but required manufacturers to provide more vaccine safety and efficacy data in their ongoing phase IV trial. However, after press coverage and ongoing legal troubles, the manufacturer decided to withdraw LYMErix™ in Februrary 2002, citing poor market performance as the primary reason for withdrawing the product. However, it is important to note that a significant proportion of the fear and pushback against the vaccine were derived from the extensive media coverage detailing these moving anecdotal stories of those experiencing adverse vaccine effects, whereas little attention was dedicated to the benefits of preventing Lyme disease. While the practicing physicians who witnessed these benefits firsthand spoke during the advisory panel, their ability to communicate these benefits to patients remained limited as mainstream media focused on the stories of those that experienced the adverse effects (14).
This pattern of early idealization to sudden condemnation was also seen with other vaccines released around this time, such as the RotaShield™ vaccine and other early childhood vaccinations like the mumps-measles-rubella (MMR) vaccine. The fear mongering surrounding vaccinations significantly eroded the public’s trust in childhood vaccinations programmes, an effect still observed at the time of writing. Perhaps if the LYMErix™ vaccine had been released ten years earlier or later, the media and the public may have been more receptive tof the benefits of the vaccines, and less inclined to focus on the risks (14)