A new Lyme disease vaccine is about to enter its final phase of human trialling. If all goes well it could be available by 2025, making it the first vaccine for Lyme disease to reach the market in nearly a quarter of a century.
The Phase 3 clinical trial plans to enroll at least 6,000 participants in 50 locations across the world. The vaccine requires three doses, each administered around two months apart, with a booster to be given one year after the initial protocol.
The new vaccine, called VLA15, targets the outer surface protein A (OspA) of the bacteria that causes Lyme disease. The formulation being tested is multivalent, targeting six different iterations of the OspA protein, hopefully covering the most common types of Lyme bacteria in both Europe and North America.
“We are extremely pleased to reach this important milestone in the development of VLA15,” said Juan Carlos Jaramillo, chief medical officer at Valneva, the company developing the vaccine in association with Pfizer. “Lyme disease continues to spread, representing a high unmet medical need that impacts the lives of many in the Northern Hemisphere. We look forward to further investigating the VLA15 candidate in Phase 3, which will take us a step closer to potentially bringing this vaccine to both adults and children who would benefit from it.”
The trial is expected to run until at least late 2024. If successful, preliminary data should come in early 2025, with a market application to the US Food and Drug Administration (FDA) not far behind.
There is currently no human Lyme disease vaccine commercially available. However, a vaccine was previously developed in the late 1990s but controversially withdrawn from the market after unproven reports of side effects.
Called LYMErix, the prior vaccine was approved by the FDA in 1998 following exceptional clinical trial results finding 80% efficacy against Lyme disease. The rise and fall of LYMErix has been dubbed “a cautionary tale” of bad public health communication and hyperbolic anti-vaccine sentiment.
In the year after the vaccine was authorized a small number of autoimmune side effects began to be reported. Primarily musculoskeletal complaints such as arthritis, these complaints were initially amplified by the media before being subject to several high-profile FDA reviews.
By 2001 the hysteria had reached a fever pitch, with a class action lawsuit directed at the vaccine manufacturer on behalf of more than 100 people who claimed harmful adverse effects from LYMErix. Despite the anecdotal claims, nearly 1.5 million doses of the vaccine had been administered to that point and no unusual side effects could be determined.
“The arthritis incidence in the patients receiving Lyme vaccine occurred at the same rate as the background in unvaccinated individuals,” explained a pair of researchers who subsequently studied the LYMErix story. “In addition, the data did not show a temporal spike in arthritis diagnoses after the second and third vaccine dose expected for an immune-mediated phenomenon. The FDA found no suggestion that the Lyme vaccine caused harm to its recipients.”
Ultimately, despite the FDA reviews finding the vaccine did not cause any adverse effects, the damage was already done. Sales for the vaccine diminished so dramatically across 2001 that LYMErix was subsequently voluntarily withdrawn from the market by its manufacturer in 2002. The next year the class action suit was settled, and the manufacturer paid legal fees to the prosecution but notably did not offer any compensation to the “victims.”
LYMErix was a subunit protein vaccine targeting OspA, much like the new VLA15 formulation that is in current trials. Despite any autoimmune effects of the old vaccine never being formally proven, researchers spent several years modifying the OspA antigen target to address any theoretical concerns of cross-immunity.
To date, the VLA15 clinical trials testing the modified OspA protein have not detected any adverse safety issues. The upcoming Phase 3 trial should offer clarity on those safety issues considering all historical analysis of the LYMErix roll-out failed to detect any problematic side effects.
Source: Pfizer