Lyme Disease Vaccine (VLA15)
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.
Initially developed by France-based Valneva SE, the VLA15 Lyme disease vaccine candidate is being tested as an alum-adjuvanted formulation and administered intramuscularly. As of 2023, VLA15 is the only Lyme disease vaccine candidate currently in advanced phase 3 clinical development. The VLA15 vaccine development program was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) in July 2017. 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.
Results from the VLA15-221 Phase 2 clinical study showed depending on the primary schedule they received (month 0-2-6 or month 0-6), participants seroconverted after the booster dose, yielding seroconversion rates (SCRs) of 95.3% and 94.6% for all OspA serotypes in all age groups, respectively. Additionally, OspA antibody titers were significantly higher one month after the booster dose compared to one month after the primary schedule, with 3.3- to 3.7-fold increases (Geometric Mean Fold Rises) in adults, 2.0- to 2.7-fold increases in adolescents and 2.3- to 2.5-fold increases in children for all serotypes.
On August 8, 2022, the Phase 3 VALOR clinical study results were confirmed. On December 1, 2022, the companies announced antibody levels remained above baseline six months after completion of a three-dose or a two-dose vaccination schedule, and higher antibody levels were observed in the three-dose vaccination schedule. Currently enrolled participants will receive their booster vaccination as planned in the second quarter of 2024 before the 2024 tick season. As of December 4, 2023, the Phase 3 clinical trial VALOR) (NCT05477524) recruited 9,437 participants across the U.S., Europe, and Canada in areas with endemic Lyme disease. The trial conclusion is expected by the end of 2025.
The journal The Lancet Infectious Diseases published results from a July 4, 2023 study that concluded Valneva's novel multivalent Lyme vaccine candidate was safe and immunogenic. A related Commentary by Ondrej Hajdusek and Jan Perner with the Czech Academy of Sciences said the VLA15 vaccine "represents a milestone in our fight against Lyme disease, and we eagerly await the results of the next clinical trials."
Valneva SE and New York-based Pfizer, Inc. announced a development and commercialization collaboration for VLA15 in April 2020. Pfizer leads the late-stage development and is controlling the vaccine's commercialization. On July 28, 2021, Pfizer revealed its Lyme disease strategy on slide #18. Pfizer indicated it could submit a Biologics License Application to the U.S. FDA as early as 2025 and a Marketing Authorization Application to the European Medicines Agency (EMA) in 2026, subject to positive data.
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.
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.
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.
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 and through a one-month post-booster. 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 feature importance to develop 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.
Valneva Financial Guidance 2023
On March 23, 2023, Valneva SE announced Total revenues of €361.3 million in 2022 compared to €348.1 million in 2021. On May 31, 2022, Valneva SE announced the appointment of Dr. Thomas Decker and Dr. Michael Pfleiderer to its Scientific Advisory Board. On June 8, 2020, Valneva announced the Pfizer collaboration agreement's antitrust-related condition precedent had been met.
Lyme Disease Vaccine News
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. VLA15 has the potential to address a high need in North America and Europe, as it has been designed to offer coverage for the most common circulating types of Borrelia bacteria that cause Lyme disease in these regions. We're excited about the ongoing trials and the progress towards potentially offering a vaccine against this disease, which can result in debilitating sequelae and excessive healthcare usage."
July 4, 2023 - The Lancet published results from a study and a related comment.
May 24, 2023 - "It is difficult to produce a Lyme disease vaccine because the Lyme disease bacteria exists in so many different variants. In the preliminary study, we mapped which types of Lyme disease are found in Europe and which the vaccine needs to cover", says Johan Sanmartin Berglund.
March 1, 2023 - Valneva SE management is presenting Lyme disease vaccine updates at the Cowen 43rd Annual Healthcare Conference on March 7, 2023.
February 17, 2023 - Pfizer Inc. and Valneva SE announce that Pfizer, the study sponsor, has decided to discontinue a significant percentage of U.S. participants in the Vaccine Against Lyme for Outdoor Recreationists Phase 3 clinical study.
January 18, 2023 - Nature Biotechnology published: Chikungunya and Lyme vaccines make headway.
December 1, 2022 - "Rates of Lyme disease continue to increase globally, underscoring the importance of a vaccine that may help protect both adults and children," said Annaliesa Anderson, Ph.D., SVP and Chief Scientific Officer of Vaccine Research & Development at Pfizer.
October 6, 2022 - The Lancet Infectious Disease published the results of a clinical study on Lyme disease treatment. This data supports seven days of oral doxycycline treatment for adult European patients with solitary erythema migrans, permitting less antibiotic exposure than current guideline-driven therapy.
September 8, 2022 - The Luzerne County Fair in Pennsylvania is recruiting people for a phase 3 clinical trial evaluating a Lyme disease vaccine candidate.
August 11, 2022 - Valneva announced Excellent progress on late-stage Lyme Disease Vaccine Candidate VLA15: Phase 3 study was initiated in August 2022, and other positive Phase 2 results were reported, including first pediatric data.
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.
July 29, 2022 - Lyme disease vaccine clinical trial will be conducted on Block Island, reported Block Island Times. The phase 3 study, An Efficacy, Safety, Tolerability, Immunogenicity, and Lot-Consistency Clinical Trial of a 6-Valent OspA-Based Lyme Disease Vaccine (VLA15) (VALOR), was updated on August 1, 2022.
July 11, 2022 - MVTimes reported a Phase 3 study of VLA15 will take place on the Vineyard, according to Michael Loberg, president of Vineyard Medical Care.
June 13, 2022 - A new study published by the BMJ found the three regions with the highest reported Borrelia burgdorferi sensu lato seroprevalence were Central Europe (21%), Eastern Asia (16%), and Western Europe (13.5%). At the other end of the scale, the regions with the lowest reported seroprevalence were the Caribbean (2%), Southern Asia (3%), and Oceania (nearly 5.5%).
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).
February 8, 2022 - Pfizer confirmed a planned Phase 3 clinical trial would evaluate VLA15 in subjects five years of age and above and is expected to be initiated in 2022, subject to regulatory approval.
February 4, 2022 - Valneva SE and Pfizer Inc planned to proceed with a three-dose primary series vaccination schedule in a planned Phase 3 clinical trial. The Lyme disease trial will evaluate VLA15 in adults and pediatric subjects five years of age and above and is expected to be initiated in 2022, subject to regulatory approval.
October 8, 2021 - Barrons published an article: A Lyme Disease Vaccine From Pfizer and Valneva Will Have to Avoid the Pitfalls of the Past.
September 28, 2021 - Valneva SE announced further positive Phase 2 results, including booster response, for Lyme disease vaccine candidate VLA15.
August 18, 2021 - The journal Frontiers in Medicine published Recent Progress in Lyme Disease and Remaining Challenges.
July 28, 2021 - New York-based Pfizer, Inc. published its Lyme disease vaccine strategy on slide #18 of its final results presentation. And presented Phase 2 Efficacy: >90% of subjects seroconvert to all six serotypes common in the U.S. & E.U. with a 3-dose vaccination schedule.
November 3, 2020 - Valneva reported a serum bactericidal assay (SBA) assessing the functional immune response against Lyme disease after vaccination with VLA15, which 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 Jan 23, 2017, and Jan 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 titre 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. Estimated Primary Completion Date: 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.