The potential for a new Lyme disease vaccine

Growing need for proactive measures

Lyme disease, caused by Borrelia burgdorferi transmitted through infected Ixodes ticks, is the most prevalent vector-borne infectious disease in the Northern hemisphere (1), often leading to long-lasting consequences. The United States has only 63,000 reported cases of Lyme disease, even though recent data estimates 476,000 people may be diagnosed and treated annually (2), while 65,500–85,000 (3) cases are reported annually with an estimated 200,000 diagnosed and treated in Europe (4). Consequently, the actual cases are often overlooked or misinterpreted and vastly underreported. 

Early symptoms such as erythema migrans (5), a bullseye-shaped rash, or nonspecific symptoms like fatigue, fever, and headache can be easily missed. If untreated, Lyme disease can progress to serious complications affecting the skin, joints, heart, or nervous system. Unfortunately, the disease’s high prevalence persists despite increasing awareness, particularly in areas where it is endemic and up to half of surveyed ticks can carry Borrelia bacteria.

Preventative measures such as insect repellents and checking for ticks are recommended but have limited impact on reducing Lyme disease cases. Research published in BMC Infectious Diseases shows that a single dose of antibiotics, if administered early, decreased the likelihood of developing Lyme disease following a tick bite compared to placebo (1). However, early intervention is crucial as, if left untreated because of a missed diagnosis, chronic outcomes can develop, which are unresponsive to typical Lyme disease treatment. The increase in cases may also be linked to an expanded geographic range for ticks.

With both the prevalence and geographic range of Lyme disease increasing, vaccination could help prevent the disease and ease its burden.

A vaccine candidate

In April of 2020, responding to this need, Pfizer Inc and Valneva SE announced a collaboration to develop VLA15 (6), an innovative vaccine candidate against Lyme disease. There are currently no approved human vaccines for Lyme disease. With two Phase 3 trials in progress, VLA15 is the most advanced Lyme disease vaccines candidate currently in clinical development. 

VLA15 targets the outer surface protein A (OspA) of Borrelia burgdorferi, inhibiting its ability to infect humans. The vaccine has a unique mechanism whereby, once vaccinated, the recipient generates antibodies against the OspA protein and, after receiving a tick bite, the antibodies go into the feeding tick along with the blood meal and neutralize the Borrelia bacteria, preventing it from being transmitted to the host and causing Lyme disease. Phase 2 trials demonstrated VLA15’s safety and ability to generate strong immune responses in both adults and children. 

A single type of Borrelia causes almost all the Lyme disease in the U.S. However, in Europe, there is a broader range of variants, including the U.S. species (4). VLA15 has been designed to offer coverage for the most common circulating types of Borrelia bacteria that cause Lyme disease in both regions. This vaccine holds promise not only for preventing Lyme disease but also for addressing its increasing geographic spread and diagnosis rates. This alum-adjuvanted, intramuscular formulation covers the six most common OspA serotypes in North America and Europe.

Phase 3 clinical trials

Building on successful Phase 1 and 2 clinical trial results, Pfizer Inc. and Valneva SE announced that they have completed recruitment for Phase 3 trial Vaccine Against Lyme for Outdoor Recreationists (VALOR) (NCT05477524) for Lyme disease vaccine candidate VLA15 (7).

The Phase 3 VALOR trial, which initiated in August of 2022, aims to confirm the vaccine’s efficacy, safety, and immunogenicity in 9,437 participants aged five and older across endemic regions in the U.S., Europe, and Canada. As part of the primary series, participants receive three doses of VLA15 or a saline placebo (1:1 ratio) within the first year, and one booster dose approximately one year after completion of the primary immunization (8). 

The VLA15 candidate has demonstrated a strong immune response and had a favorable safety profile across all dose and age groups in pre-clinical and clinical trials so far. No vaccine-related serious adverse events (SAEs) and no safety concerns were observed by an independent Data Safety Monitoring Board (DSMB) (9). A second Phase 3 trial (C4601012), aiming to provide further evidence on the safety profile of VLA15 in the pediatric population, is also fully recruited. 

The VALOR trial is expected to be concluded by the end of 2025. Subject to positive Phase 3 data, Pfizer and Valneva aim to submit a Biologic License Application to the Food and Drug Administration and Marketing Authorization Application to the European Medicines Agency in 2026. 

References

1. Guozhong, Z., Xu, Z., Zhang Y., et al. Antibiotic prophylaxis for prevention against Lyme disease following tick bite: an updated systematic review and meta-analysis. BMC Infectious Diseases. Published November 8, 2021. https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06837-7
2. Lyme Disease Surveillance & Data. https://www.cdc.gov/lyme/data-research/facts-stats/index.html. Last Updated May 15, 2024.
3. Schwameis M, Kündig T, Huber G, et al. Topical azithromycin for the prevention of Lyme borreliosis: a randomised, placebo-controlled, phase 3 efficacy trial. Lancet Infect Dis. 2017;17(3):322–9. https://doi.org/10.1016/S1473-3099(16)30529-1.
4. Marques, A.R., Strle, F., Wormser, G.P. Comparison of Lyme Disease in the United States and Europe. Emerging Infectious Diseases. Published August 2021. https://wwwnc.cdc.gov/eid/article/27/8/20-4763_article
5. Stanek et al. Lyme borreliosis. The Lancet. Published September, 2011 https://doi.org/10.1016/S0140-6736(11)60103-7
6. Valneva and Pfizer Announce Collaboration to Co-Develop and Commercialize Lyme Disease Vaccine, VLA15. Valneva. https://valneva.com/press-release/valneva-and-pfizer-announce-collaboration-to-co-develop-and-commercialize-lyme-disease-vaccine-vla15/ Published April 30, 2020. 
7. Pfizer and Valneva Initiate Phase 3 Study of Lyme Disease Vaccine Candidate VLA15. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-valneva-initiate-phase-3-study-lyme-disease
8. An Efficacy, Safety, Tolerability, Immunogenicity, and Lot-Consistency Clinical Trial of a 6-Valent OspA-Based Lyme Disease Vaccine (VLA15) (VALOR). Last updated June 20, 2024. https://clinicaltrials.gov/study/NCT05477524?cond=Lyme%20Disease&term=VALOR&intr=Vaccine&rank=1
9. Comtedt, P. Shulet, W., Minke, A. et al. The novel Lyme borreliosis vaccine VLA15 how’s broad protection against Borrelia species expressing six different OspA serotypes. PLOS One. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581183/. Published September 1, 2017.