Lyme Disease Vaccine (VLA15) Clinical Trials, Dosage, Side Effects, Usage
Lyme disease candidate VLA15 is a multivalent recombinant protein vaccine targeting Borrelia's outer surface protein A (OspA). It is designed for prophylactic, active immunization against Lyme disease to protect people against most human pathogenic Borrelia species. OspA is one of the most dominant surface proteins expressed by the bacteria when present in a tick. The VLA15 vaccine protects humans by raising antibodies that prevent Borrelia from migrating from ticks after a bite.VLA15 is designed to cover about 97% of Borrelia in North America and Europe. VLA15 is being tested as an alum-adjuvanted formulation and administered intramuscularly. As of October 10, 2024, VLA15 is the only Lyme disease vaccine candidate in advanced phase 3 clinical development.
A study published in 2017 found that immunological memory could be confirmed by a three-priming immunization and a booster dose administered five months later. In addition, the half-lives of anti-OspA serotype-specific antibody titers after booster immunization were longer than after primary vaccination. In addition, the clinical data showed that VLA15 induced protection in mice against challenges with four clinically relevant Borrelia species (B. burgdorferi, B. afzelii, B. garinii, and B. bavariensis) expressing five of the six OspA serotypes included in the vaccine.
On September 3, 2024, Valenva SE announced the VLA15-221 Phase 2 study posted strong immune responses one month after a second booster dose (month 31) in pediatric and adult populations. Significant anamnestic antibody response was observed across all six serotypes, consistent with previous results, and a favorable safety profile of VLA15 was observed in all age groups and for all vaccinations. Juan Carlos Jaramillo, M.D., Chief Medical Officer of Valneva, said, "We are encouraged by these data, which support the potential benefit of booster doses across all examined age groups. Each new set of positive data brings us one step closer to potentially bringing this vaccine to adults and children living in areas where Lyme disease is endemic."
On May 31, 2024, The Lancet published an article titled "Optimization of Dose Level and Vaccination Schedule for the VLA15 Lyme Borreliosis Vaccine Candidate Among Healthy Adults: Two Randomized, Phase 2 Studies" provides a detailed analysis of the VLA15-201 and VLA15-202 trial results, which investigated different dose levels and vaccination schedules of VLA15, a hexavalent Lyme disease vaccine candidate targeting most prevalent Borrelia species (serotype 1-6) in North America and Europe.
Valneva SE and New York-based Pfizer, Inc. announced a development and commercialization collaboration for VLA15 in April 2020. Pfizer leads the vaccine's late-stage development and commercialization. Pfizer presented its Lyme disease strategy on slide #18, indicating it could submit a Biologics License Application to the U.S. Food and Drug Administration (FDA) as early as 2025 and a Marketing Authorization Application to the European Medicines Agency (EMA) in 2026, subject to positive phase 3 study data. The FDA granted the VLA15 vaccine development program Fast Track designation in July 2017.
Valneva SE (Nasdaq: VALN; Euronext Paris: VLA) is a specialty vaccine company located in Saint-Herblain, France, that provides prevention against diseases with significant unmet medical needs. The Company conducted Investor Day 2024 on October 10, 2024.
Lyme Disease Vaccine VLA15 Indication
Vaccination with VLA15 is designed to prevent Lyme disease in people. According to the U.S. Centers for Disease Control and Prevention (CDC), Lyme disease is a systemic infection caused by Borrelia bacteria transmitted to humans by infected Ixodes ticks. It is considered the most common vector-borne illness in the Northern Hemisphere and Europe. Nearly all human infections are caused by three B burgdorferi sensu lato genospecies: Borrelia garinii, Borrelia afzelii, and B burgdorferi sensu stricto. All three species cause Lyme borreliosis in Europe, whereas only B burgdorferi sensu stricto causes Lyme borreliosis in the U.S.
On June 13, 2022, the journal BMJ Global Health reported that about 14% of the world's population probably has or has had tick-borne Lyme disease, as indicated by the presence of antibodies in the blood, a pooled data analysis of the available evidence. In addition, the reported estimated global Bb seropositivity is relatively high, with the top three regions being Central Europe, Western Europe, and Eastern Asia.
A report from FAIR Health, from 2007 to 2021, indicates Lyme diagnoses rose 357% in rural regions and 65% in urban areas. In June and July, insurance claim lines with Lyme disease diagnoses were more common in rural than urban areas. But from November to April, claim lines with Lyme disease diagnoses occurred more often in urban than rural areas. In addition, the CDC published 'Comparison of Lyme Disease in the United States and Europe' on July 18, 2021. Patients with erythema migrans more often have concomitant systemic symptoms in the United States than in Europe.
Lyme Disease Vaccine VLA15 Mechanism of Action
Valneva has developed an innovative mechanism of action for VLA15: Upon feeding, the tick ingests antibodies from the host blood. In the tick gut, OspA antibodies bind to B. burgdorferi’s OspA. OspA-bound antibodies inhibit the dissemination of bacteria in the tick, blocking transmission to the host (people).
Lyme Disease Vaccine VLA15 Dosage
The randomized, placebo-controlled, Phase 3 VALOR study participants received a three-dose (Month 0-2-6) or a two-dose (Month 0-6) vaccination schedule. Higher antibody levels were observed in the three-dose vaccination schedule. A fourth 'booster' dose is being evaluated in 2024/2025. The Lancet Infectious Diseases published an article, Volume 24, Issue 9, in September 2024, which supports the further clinical development of VLA15 using the 180 μg dose and 0-2-6-month schedule associated with the most significant immune responses. Valneva clarified on October 10, 2024, that VLA15 dosage could include annual booster doses.
Lyme Disease Vaccine VLA15 Side Effects
In the VLA15-202 phase 2 study, VLA15 was found safe and well-tolerated across all doses and age groups. No related serious adverse events were observed in any treatment group or during a one-month post-booster period. VLA15-221's main safety and immunogenicity readout in adults was performed at month seven. The clinical trial is ongoing to assess the safety and immunogenicity of VLA15 in a pediatric population aged five years and above.
Lyme Disease Tests
The U.S. CDC currently recommends a 2-step testing process for Lyme disease. Both steps are required and can be done using the same blood sample.
The peer-reviewed journal Cell Reports published a study on November 15, 2022: Gene set predictor for post-treatment Lyme disease. By distilling gene sets from this study with gene sets from other sources, the researchers identified a subset of genes highly expressed in the cohorts but not already established as biomarkers for inflammatory response or other viral or bacterial infections. They further reduce this gene set by highlighting the importance of developing an mRNA biomarker set capable of distinguishing healthy individuals from those with acute L.D. or PTLD as a candidate for translation into an L.D. diagnostic.
Lyme Disease Vaccine VLA15 News
October 10, 2024 - Vlaneva SE presented an investor update.
August 16, 2024 - Do We Need a Lyme Disease Vaccine? Plotkin, Stanley A. MD, The Pediatric Infectious Disease Journal.
September 19, 2024 - U.S. CDC - New Clinical Tools and Resources to Support Patients with Prolonged Symptoms and Concerns about Lyme Disease.
September 3, 2024 - Annaliesa Anderson, Ph.D., Senior Vice President and Head of Vaccine Research and Development at Pfizer, commented in a press release, "Together with our partner Valneva, we look forward to progressing our vaccine candidate in the ongoing Phase 3 clinical trials."
December 4, 2023 - Juan Carlos Jaramillo, M.D., Chief Medical Officer of Valneva, said in a press release. "The completion of enrollment is an important milestone in developing a potential vaccine for Lyme disease."
August 11, 2022—Valneva announced excellent progress on late-stage Lyme Disease Vaccine Candidate VLA15. The Phase 3 study was initiated in August 2022, and other positive Phase 2 results, including the first pediatric data, were reported.
August 8, 2022 - Pfizer Inc. and Valneva SE announced the initiation of the Phase 3 clinical study' Vaccine Against Lyme for Outdoor Recreationists' to investigate the efficacy, safety, and immunogenicity of the Lyme disease vaccine candidate, VLA15.
April 26, 2022 - Valneva SE and Pfizer Inc. reported positive Phase 2 pediatric data for their Lyme disease vaccine candidate, VLA15, in pediatric participants (5-17 years old).
July 28, 2021—Pfizer, Inc. published its Lyme disease vaccine strategy on slide #18 of its final results presentation. This assay presented Phase 2 Efficacy: >90% of subjects seroconvert to all six serotypes common in the U.S. and E.U. with a 3-dose vaccination schedule.
November 3, 2020—Valneva reported a serum bactericidal assay assessing the functional immune response against Lyme disease after vaccination with VLA15. This assay was conducted for the first time in VLA15-202 and demonstrated the functionality of antibodies against all OspA serotypes.
July 22, 2020 - Valneva SE announced positive initial results for its first Phase 2 study (VLA15-201) of Lyme disease vaccine candidate VLA15. The vaccine was found immunogenic across all dose groups tested.
April 30, 2020 – Valneva SE and Pfizer announced a collaboration to develop and commercialize Valneva's Lyme disease vaccine candidate VLA15, which is currently in Phase 2 clinical studies.
July 1, 2019 - A second Phase 2 clinical trial for developing Lyme disease vaccine candidate VLA15 has been announced. Following the Run-In phase for Valneva's first Phase 2 study, VLA15-201, the two dosage levels (135µg and 180µg) have been selected for further development based on Data and Safety Monitoring Board clearance.
VLA15 Clinical Trials
VLA15 continues under clinical trials to test its Immunogenicity Safety and dosing.
On July 4, 2023, The Lancet Infectious Diseases wrote. Between January 23, 2017, and January 16, 2019, of 254 participants screened for eligibility, 179 were randomly assigned into six groups: alum-adjuvanted 12 μg (n=29), 48 μg (n=31), or 90 μg (n=31) and non-adjuvanted 12 μg (n=29 participants), 48 μg (n=29), or 90 μg (n=30). VLA15 was safe and well tolerated; most adverse events were mild or moderate. Overall, adverse events were more frequent in the 48 μg and 90 μg groups (range 28−30 participants [94−97%]) when compared with the 12 μg group (25 [86%] participants, 95% CI 69·4–94·5) for adjuvanted and non-adjuvanted groups. Common local reactions were tenderness (151 [84%] participants; 356 events, 95% CI 78·3−89·4) and injection site pain (120 [67%]; 224 events, 59·9–73·5); most frequent systemic reactions were headache (80 [45%]; 112 events, 37·6–52·0), excessive fatigue (45 [25%]; 56 events, 19·4–32·0), and myalgia (45 [25%]; 57 events, 19·4–32·0). A similar safety and tolerability profile was observed between adjuvanted and non-adjuvanted formulations. The majority of solicited adverse events were mild or moderate. VLA15 was immunogenic for all OspA serotypes with higher immune responses induced in the adjuvanted higher dose groups (geometric mean titer range 90 μg with alum 61·3 U/mL–321·7 U/mL vs. 23·8 U/mL–111·5 U/mL at 90 μg without alum).
On February 17, 2023, Pfizer and Valnea announced that Pfizer, as the study VALOR sponsor, has decided to discontinue a significant percentage of participants in the U.S. who had been enrolled in the VALOR Phase 3 clinical study. These study participants, representing approximately half of the total recruited participants in the trial, are discontinued following violations of Good Clinical Practice at specific clinical trial sites run by a third-party clinical trial site operator. The discontinuation of these participants was not due to any safety concerns with the investigational vaccine and was not prompted by a participant-reported adverse event. The companies confirmed on March 23, 2023, that they intend to work with regulatory authorities and, as previously announced, aim for Pfizer to potentially maintain the original submission timelines, pending successful completion of the Phase 3 studies and subject to the agreement of these regulatory agencies to proposed modifications of the clinical trial plan.
Clinical Study VLA15-221 is a randomized, observer-blind, placebo-controlled Phase 2 study. The first clinical study with VLA15 enrolls a pediatric population aged five years and older. 294 healthy adult participants received VLA15 at two different immunization schedules (month 0-2-6 [N=97] or month 0-6 [N=90]) or three doses of placebo (month 0-2-6 [N=107]). Vaccine recipients received VLA15 at a dose of 180 µg, which was selected based on data generated in the two previous Phase 2 studies. The main safety and immunogenicity readout in adults was performed at month 7. A subset of participants will receive a booster dose of VLA15 or placebo at month 18 (booster phase) and will be followed for three additional years to monitor antibody persistence. The VLA15-221 trial is ongoing to assess the safety and immunogenicity of VLA15 in a pediatric population aged five years and above.
On August 8, 2022, the companies announced the initiation of a Phase 3 clinical study, Vaccine Against Lyme for Outdoor Recreationists (VALOR), to investigate the efficacy, safety, and immunogenicity of their investigational Lyme disease vaccine candidate, VLA15. The Estimated Primary Completion Date is December 31, 2024.
On July 22, 2020, the Lyme disease Phase 2 study VLA15-201 announced it met its endpoints. Compared to Phase 1, the higher doses used in this trial elicited higher antibody responses across all serotypes. An encouraging immunogenicity profile was confirmed, including older adults.
