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Home » Lyme vaccine phase 2 clinical trials results — safe and effective

Lyme vaccine phase 2 clinical trials results — safe and effective


I like to keep up-to-date with the new Lyme disease vaccine clinical trials for a couple of reasons — first, Lyme disease is dangerous, and second, we had an excellent vaccine 30 years ago. Unfortunately, it was pulled from the market because of ridiculous claims by anti-vaxxers.

New results from the Lyme vaccine phase 2 clinical trials have been published while the phase 3 trials are just starting in several locations across the USA and Europe.

As I usually do, I will review Lyme disease (since there’s a lot of misinformation about it) and the results from the phase 2 clinical trials.

What is Lyme disease?

Lyme disease is an infectious disease caused by at least three species of bacteria belonging to the genus Borrelia. Of the three species, Borrelia burgdorferi is the main cause of Lyme disease in North America, whereas Borrelia afzelii and Borrelia garinii are more prevalent in Europe. The disease was named after the towns of Lyme and Old Lyme, Connecticut, where several cases were initially identified in 1975.

Borrelia is transmitted to humans when bitten by infected ticks which belong to a few species of the genus Ixodes, called “hard-bodied” ticks. Although deer ticks, Ixodes scapularis, Ixodes pacificus, or Ixodes ricinus, are commonly considered to be vectors for Borrelia infection, some of the other species in the Ixodes genus can transmit the disease. Lyme disease is the most common tick-borne disease in the United States.

There are several initial symptoms of Lyme disease – fever, headache, fatigue, depression, and a circular skin rash called erythema migrans (EM). If the Borrelia infection is not treated quickly, further symptoms may appear which involve the joints, heart, and central nervous system.

There is generally only one known treatment for a Borrelia infection – antibiotics, which may include doxycycline, amoxicillin, and cefuroxime. Generally, the symptoms of the infection resolve after antibiotic treatment.

While the true incidence of Lyme disease is unknown, it is estimated to affect approximately 476,000 people annually in the USA and 130,000 people in Europe.

As I’ve written previously, the existence of “chronic Lyme disease,” a condition that some claim is a set of vague symptoms that are claimed to be a consequence of a permanent B. burgdorferi infection and somehow persists after antibiotic therapy. The existence of chronic Lyme disease is not supported by robust scientific evidence published in peer-reviewed, high-impact-factor biomedical journals.

person holding laboratory flask
Photo by Chokniti Khongchum on Pexels.com

Lyme vaccine candidate

Luckily for those in areas with endemic Lyme disease, a small French vaccine company, Valneva, has been developing a new Lyme disease vaccine, code-named VLA15, a multivalent vaccine that targets one of the most dominant outer surface proteins of Borrelia bacteria. Valneva has partnered with Pfizer to complete clinical trials and to bring the vaccine to the market in North America and Europe.

The VLA15 vaccine contains three lipidated fusion proteins that each link the C-terminal domains of two OspA (outer surface protein A of B. burgdorferi) serotypes so that it targets six serotypes in total. In animal studies, VLA15 induced protection in mice from Borrelia species common in North America (B. burgdorferi) and Europe (B. burgdorferiB. afzeliiB. garinii, and B. bavariensis).

Preclinical studies showed that the vaccine was broadly effective against Lyme disease. These types of studies are how most vaccines are developed, by trying them in animal models.

Soon thereafter, Phase 1 clinical trials, in which the vaccine is tested on healthy volunteers, were successful.  Valneva proceeded with two Phase 2 clinical trials.  

The VLA15 Lyme disease vaccine candidate was granted a Fast Track designation by the FDA in July 2017. Because this designation is often misunderstood, I’ll try to explain it. Fast Track is granted by the FDA to investigational products that are under development for serious conditions and have the potential to fulfill an unmet medical need, a Lyme disease vaccine certainly meets that standard.

The process facilitates clinical development and expedites the review of new drugs and vaccines. It accelerates the availability of promising products on the market.

This does not mean that the vaccine gets less than a thorough review. It does not mean that Valneva and Pfizer can skip any of the phases of human clinical trials. Fast Track speeds up the review process. The process does not become any easier.

Lyme disease vaccine phase 2 clinical trials paper

In a paper published on 31 May 2024 in the prestigious journal Lancet Infectious Diseases, Susanne Eder-Lingelbach, MSc, of Valneva Austria in Vienna, and colleagues examined phase 2 clinical trial results regarding the immunogenicity and safety of a three-dose regimen of the VLA-15 Lyme disease vaccine candidate.

For study one, 573 participants were screened and randomly assigned to treatment groups between 21 December 2018, and 26 September 2019. For study two, 248 participants were screened and randomly assigned between 26 June and 3 September 2019. In study one, 29 participants were assigned to receive 90 μg VLA15, 215 to 135 μg, 205 to 180 μg, and 124 to placebo. In study two, 97 participants were assigned to receive 135 μg VLA15, 100 to 180 μg, and 51 to placebo.

Here are the key results:

  • In study one, which used a 0/1/2-month schedule, mean GMTs ranged from 101.9 to 283.2 units/mL for the 135-μg vaccine dose and 115.8 to 308.6 units/mL for the 180-μg dose, depending on the OspA serotype.
  • After administration of VLA15 on a 0/2/6-month vaccine schedule (study two), OspA-specific IgG (antibodies against the two OspA targets) geometric mean titers (GMTs) ranged from 278.5 to 545.2 units/mL with the 135-μg vaccine dose at 1 month after the third dose, and 274.7 to 596.8 units/mL for the 180-μg dose. This showed a statistically significant increase in antibodies against Borrelia bacteria.
  • The 180-µg dose generated the best OspA-specific antibody response in both studies.
  • Participants who received the VLA15 vaccine reported adverse events more frequently than the placebo groups. In studies one and two, 94% and 96% of participants reported solicited local adverse events, respectively, compared with 26% and 35% in the placebo groups. The most common local and minor adverse events were tenderness and pain.
  • Systemic adverse events in the vaccine groups were reported by 69% and 74% of participants in studies one and two, respectively, versus 43% and 51% of those who received placebo. The most commonly reported systemic adverse events were myalgia, headache, and fatigue, which were primarily mild or moderate. These are common to all vaccines as it is a result of stimulating the immune system. These are not serious.
  • Serious unsolicited adverse events were infrequent, reported by 2% and 4% in studies one and two, respectively, although they were not more frequent than background levels of the events. No deaths were reported.

The authors concluded that “VLA15 was safe, well tolerated, and elicited robust antibody responses to all six OspA serotypes.”

Phase 3 clinical trial

Valneva and Pfizer announced on 9 August 2022 the initiation of Phase 3 clinical trials, Vaccine Against Lyme for Outdoor Recreationists (VALOR), to investigate the safety, effectiveness, and immunogenicity of the Lyme disease vaccine candidate VLA15. As of today, VLA15 is the only Lyme disease vaccine that is currently in clinical development

Pfizer and Valneva are going to recruit approximately 18,000 healthy participants 5 years and older from areas with high levels of endemic Lyme disease to receive the VLA15 vaccine or a placebo. Just to be utterly clear, each participant will have about a 50% chance of receiving VLA15 and about a 50% chance of receiving a placebo. A subset of participants will receive VLA15 from 3 different lots or a placebo (1:1:1:3 ratio) to assess lot equivalence. The participants will have to receive three doses of VLA15 (180 µg).

The study will be conducted at up to 50 sites in areas where Lyme disease is highly endemic, including Poland and parts of the USA. The USA study centers are in Connecticut, Massachusetts, New Jersey, New York, Pennsylvania, and Rhode Island.

Pending successful completion of the Phase 3 study, Pfizer could potentially submit a Biologics License Application to the U.S. FDA along with a Marketing Authorisation Application to the European Medicines Agency in 2025. It will be a few years before the vaccine is approved and becomes available widely.

Summary

Lyme disease is a dangerous infection that is endemic to many parts of the USA and Europe. Preventing it with a safe and effective vaccine is an important goal.

The phase 2 clinical trials were successful in showing that the vaccine showed strong immunogenicity against Lyme disease bacteria. Also, the studies showed that the vaccine was very safe.

Phase 3 clinical trials will have endpoints of preventing Lyme disease and will gather more information about the safety of the vaccine. Although I am not completely certain, I believe that the investigators are still recruiting patients for the phase 3 studies. You can email ClinicalTrials.gov_Inquiries@pfizer.com, to volunteer if you live in the areas being targeted by the trial.

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Michael Simpson

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