Vaccine Info

Lyme Disease Vaccine (VLA15)

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August 11, 2022
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Lyme Disease Vaccine (VLA15)

Lyme Disease vaccine candidate VLA15 is a multivalent recombinant protein vaccine targeting the outer surface protein A (OspA) of Borrelia, 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.

Initially developed by Valneva SE, the VLA15 vaccine candidate is tested as an alum-adjuvanted formulation and administered intramuscularly. The Lyme disease vaccine VLA15 confers protection by raising antibodies that prevent Borrelia from migrating from ticks to humans after a bite. The VLA15 program was granted Fast Track designation by the U.S. FDA in July 2017. As of August 8, 2022, VLA15 is the only active vaccine program in human clinical development against Lyme disease.

study published in 2017 found following a three priming immunization and a booster dose administered five months later, the induction of immunological memory could be confirmed. Thus, the antibody titers after the booster dose were increased considerably. In addition, the half-lives of anti-OspA serotype-specific antibodies after administration of the booster immunization were longer than after primary vaccination. In addition, the data shows 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. 

Valneva 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 June 8, 2020, Valneva announced the Pfizer collaboration agreement's antitrust-related condition precedent had been met. On July 28, 2021, Pfizer revealed its Lyme disease strategy on slide #18. On February 4, 2022, Valneva and Pfizer announced a three-dose primary series vaccination schedule in a planned Phase 3 clinical trial expected to be initiated in the third quarter of 2022, subject to regulatory approval.

On August 8, 2022, the Phase 3 VALOR was confirmed. As a result, Pfizer could submit a Biologics License Application to the U.S. FDA as early as 2025.

Valneva SE (Nasdaq: VALN; Euronext Paris: VLA) is a Saint-Herblain, France-located specialty vaccine company providing prevention against diseases with significant unmet medical needs.

VLA15 History

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. And encouraging immunogenicity profile confirmed, including older adults. The endpoint readout was immunogenicity at Day 85 (1-month after finalization of primary immunization).

On September 28, 2021, the Valneva confirmed participants who received a complete primary vaccination series with 180 µg doses of VLA15 were invited to continue the VLA15-202 study in a booster extension phase and were randomized to receive an additional 180 µg dose of VLA15 (N=39) or placebo (N=19) at Month 18. Administration of a booster dose elicited a strong anamnestic response yielding a 2.9-fold (ST3) to 4.2-fold (ST1, ST4) increase (Geometric Mean Fold Rise) in anti-OspA IgG antibody titers compared with titers observed after primary immunization. In addition, all participants seroconverted to anti-OspA IgG after the booster dose, meaning Seroconversion Rates (SCRs) were 100% for all OspA serotypes. Additionally, seropositive subjects at baseline needed to show at least a 4-fold increase in anti-OspA IgG compared to baseline titer. Serum Bactericidal activity Assays demonstrated the functionality of elicited antibodies, leading to SCRs ranging from 86.8% (ST2) to 100.0% (ST3) after the booster.

VLA15 Indication

According to the U.S. 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 USA.

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 as Central Europe, Western Europe, and Eastern Asia. 

On March 15, 2022, JCI published a study from Tufts University that found 'Use of host lipid by the Lyme disease spirochete may lead to biomarkers.' The UK Health Security Agency blog post on April 13, 2022:  What is Lyme disease, and why do we need to be tick aware?

A report from FAIR Health, from 2007 to 2021, indicates Lyme diagnoses rose 357% in rural regions and 65% in urban areas. And 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. - In the United States, patients with erythema migrans more often have concomitant systemic symptoms than in Europe.

VLA15 Dosage

Valneva has been conducting Phase 2 studies in parallel with more than 800 people. In the first study, VLA15-201, a short vaccination schedule was tested (0-1-2 months) in 572 subjects, while in the second study, VLA15-202, a more extended vaccination schedule (0-2-6 months) was tested in 246 subjects. In both studies, people received 2-dose levels (either 135µg or 180µg) of VLA15 in 3 injections or placebo.

The randomized, placebo-controlled, Phase 3 VALOR study participants will receive four doses: three doses of VLA15 180 µg or saline placebo as a primary vaccination series, followed by one booster dose of VLA15 or saline placebo (1:1 ratio).

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 were 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.

Valneva Pfizer Agreements

Valneva SE and Pfizer Inc. announced on June 20, 2022, that they have entered into an Equity Subscription Agreement and have updated the terms of their Collaboration and License Agreement for Lyme disease vaccine candidate VLA15. As part of the Equity Subscription Agreement, Pfizer will invest €90.5 ($95) million in Valneva. This investment closed on June 23, 2022.

Valneva Financial Guidance

As of August 11, 2022, Valneva expects total revenues to reach €340 million to €360 million in 2022, noting the continued recovery of travel vaccine sales, the revenue recognition linked to the EC and UK supply contracts, and the recently revised Advance Purchase Agreement with the EC for the Company’s COVID-19 vaccine. Furthermore, product sales of the Company’s travel vaccine franchise are expected to reach €70 million to €80 million, while COVID-19 product sales are expected to reach €30 million to €40 million.

Valneva VLA15 News

August 11, 2022 - Valneva announced: Excellent progress on late-stage Lyme Disease Vaccine Candidate VLA15: Phase 3 study was initiated in August 2022, and further positive Phase 2 results were reported, including first pediatric data.

August 8, 2022 - Pfizer Inc. and Valneva SE announced the initiation of 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 21, 2022 - Local media reported Dr. Alexandra Yamshchikov, Infectious Disease Physician at Rochester General Hospital, New York, said that Lyme disease cases have been going up, with three times as many ticks being found in the community over the past ten years.

July 21, 2022 - In a dvm360® interview, Brian Herrin, DVM, Ph.D., DACVM, discussed the importance of tick prevention.

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%).

May 31, 2022 - Valneva SE announced the appointment of leading vaccine experts Dr. Thomas Decker and Dr. Michael Pfleiderer to its Scientific Advisory Board.

May 18, 2022 - The Companion Animal Parasite Council is warning that vector-borne diseases, including Lyme, will pose higher-than-average risks across the USA in 2022.

May 12, 2022 - North Somerset Council in the U.K. urges people to be 'tick aware.' Health leaders are urging people to walk on paths, avoid dense vegetation and use insect repellent that repels ticks.

May 5, 2022 - Valneva confirmed Phase 3 study is expected to commence in the third quarter of 2022.

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) who received VLA15 in either the two-dose schedule (N=93) or three-dose schedule (N=97), VLA15 was found to be more immunogenic than in adults with both vaccination schedules tested. Like in adults, the immunogenicity and safety data support a three-dose primary vaccination schedule in pediatric participants in the Phase 3 study.

April 8, 2022 - Saravanan Thangamani, professor in the department of microbiology and immunology at the SUNY Upstate Medical University, indicated a 43% increase in the number of ticks submitted for testing compared to March 2021.

March 24, 2022 - U.S. Public Health Command Europe officials report an unusually high tick activity early in 2022. "Ticks can carry several potentially serious diseases," explained Lt. Col. William Washington, Public Health Command Europe's Chief of Epidemiology and Disease Surveillance. "The two most common disease ticks transmit is Lyme disease and tick-borne encephalitis."

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. announced a plan 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.

February 3, 2022 - Valneva SE reported €94.8 million of product and other revenues (excluding COVID), at the higher end of the Company's previously communicated guidance of €85 to €100 million for 2021.

December 10, 2021 - The Nebraska Department of Health and Human Services was notified of two local cases of Lyme disease. Both patients reported likely exposure around the same timeframe at sites near one another in Thurston County. In addition, ticks submitted to Creighton University and the U.S. CDC returned positive for Borrelia burgdorferi, indicating that the bacteria that causes Lyme disease is circulating in the tick population in the area. These results mark the first-ever detection of Borrelia burgdorferi in Nebraska's blacklegged tick populations and the first definitive evidence of Lyme disease cases acquired locally in the state.

November 10, 2021 - BusinessInsider published: The U.S. had a Lyme disease vaccine decades ago — but the CDC, lawsuits, and conspiracy theories derailed it.

October 29, 2021 - The Company announced the aggregate gross proceeds from its offering are expected to be approximately $88.7 million, equivalent to about €76.5 million, before deducting underwriting commissions and estimated expenses payable by the Company.

October 26, 2021 - Valneva SE announced its intention to issue and sell, subject to market conditions, 5,500,000 of its ordinary shares in a global offering to specified categories of investors. Approximately $50 million of proceeds could be used to fund further development of its Lyme VLA15 vaccine candidate through completion of Phase 2 clinical trials, including handover to Pfizer.

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 30, 2021 - Valneva SE announced that its senior management would present and participate in meetings at the Guggenheim Vaccines and Infectious Disease Conference on October 6, 2021.

September 28, 2021 - Valneva SE announced further positive Phase 2 results, including booster response, for Lyme disease vaccine candidate VLA15. Administration of a booster dose elicited a strong anamnestic response yielding a 2.9-fold (ST3) to 4.2-fold (ST1, ST4) increase (Geometric Mean Fold Rise) in anti-OspA IgG antibody titers compared with titers observed after primary immunization. In addition, all participants seroconverted to anti-OspA IgG after the booster dose, meaning Seroconversion Rates (SCRs) were 100% for all OspA serotypes. 

August 18, 2021 - The journal Frontiers in Medicine published an article: Recent Progress in Lyme Disease and Remaining Challenges.

August 10, 2021 - Valneva SE (Nasdaq: VALN; Euronext Paris: VLA) reported its consolidated financial results for the first half of the year, which ended June 30, 2021. To accelerate VLA15's pediatric development, Valneva and Pfizer initiated an additional Phase 2 trial in March 2021, VLA15-221. In July 2021, Pfizer and Valneva announced recruitment completion for VLA15-221 with a total of 625 participants, 5 to 65 years of age, randomized in the trial. The trial's objective is to show safety and immunogenicity to 5 years of age and evaluate the optimal vaccination schedule for use in Phase 3. Topline results for VLA15-221 are expected in the first half of 2022.

August 7, 2021 - JapanToday published 'Lyme disease protection: No vaccine yet, but an antibody shot could soon provide a season of immunity.'

July 28, 2021 - New York-based Pfizer, Inc. published its Lyme disease vaccine strategy on slide #18 of its finical results presentation. And presented Phase 2 Efficacy: >90% of subjects seroconvert to all six serotypes common is U.S. & E.U. with 3-dose vaccination schedule; Vaccine was safe and well-tolerated at all dose levels tested.

July 23, 2021 - The population-weighted incidence of Lyme borreliosis in western Europe has been estimated at 22 cases per 100,000 people per year, although the data varies across European countries. The highest reported incidences of Lyme borreliosis were reported in southern Sweden, while the lowest was in Italy. Other countries, including Croatia, Bulgaria, Finland, and Hungary, reported high disease incidence rates.

July 19, 2021 - Valneva and Pfizer Inc. announced that they had completed the recruitment of 625 participants, 5 to 65 years of age, for the Phase 2 trial, VLA15-221, of Lyme disease vaccine candidate, VLA15. The main safety and immunogenicity readout will be performed approximately one month after completing the primary vaccination schedule (i.e., at Month 7). The trial aims to show safety and immunogenicity down to 5 years of age and evaluate the optimal vaccination schedule for use in the Phase 3 study.

December 2, 2020 - Valneva SE announced plans to accelerate its Lyme vaccine candidate's pediatric development, VLA15, in collaboration with Pfizer Inc. With the planned initiation of study VLA15-221 in the first quarter of 2021, subject to regulatory approval. If approved, it will be the first clinical study of VLA15 to enroll a pediatric population aged 5-17 years and compare the three-dose vaccination schedule Month 0-2-6 with a reduced two-dose schedule of Month 0-6.

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 VLA15-202 and demonstrated the functionality of antibodies against all OspA serotypes. Assays, such as SBAs, are commonly used to enable a potential prediction of vaccine efficacy via the measurement of vaccine-induced functional immune responses. VLA15-202 safety and immunogenicity data at Day 208 support advancing the program with the Month 0-2-6 schedule. Valneva and Pfizer will finalize the dosage analysis and prepare for the subsequent development steps in the coming months.

October 20, 2020 - Valneva SE announced positive initial results for its second Phase 2 study (VLA15-202) of Lyme disease vaccine candidate VLA15, which investigated a vaccination schedule of Months 0-2-6 based on matching doses. VLA15 was generally safe across all doses and age groups tested. 

August 12, 2020 - A national survey was jointly created with Hollins University, Duke University, Clemson University, and the University of Rhode Island to determine if coronavirus restrictions have affected the time that people or their pets spend outdoors and if this change is associated with an increased risk of exposure to ticks.

July 22, 2020 - Valneva SE announced positive initial results for its first Phase 2 study (VLA15-201) of Lyme disease vaccine candidate VLA15, which was found immunogenic across all dose groups tested. Compared to Phase 1, the higher doses used in this trial elicited higher antibody responses across all serotypes. Seroconversion rates (SCR) in the highest dose ranged from 81.5% (ST1) to 95.8% (ST2).

May 25, 2020 - Clinicians should be aware of Lyme carditis's risk in patients presenting with atrioventricular (A.V.) block, especially those with a history of outdoor exposure in Lyme endemic areas, even if they do not endorse tick exposure or a history of erythema migrans.

April 30, 2020 – Valneva SE and Pfizer announced a collaboration to develop and commercialize Valneva's Lyme disease vaccine candidate VLA15, currently in Phase 2 clinical studies. VLA15 is the only active Lyme disease vaccine program in clinical development today and covers six prevalent serotypes in North America and Europe.

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 to go under clinical trials to test its Immunogenicity Safety and dosing. Pending successful initiation and completion of the planned Phase 3 study for VLA15, Pfizer could potentially submit a Biologics License Application to the U.S. Food and Drug Administration as early as 2025.

Valneva announced its plans to accelerate pediatric development on December 2, 2020. If approved, it will be the first clinical study of VLA15 to enroll a pediatric population aged 5-17 years and compare the 3-dose vaccination schedule Month 0-2-6 with a reduced two-dose schedule of Month 0-6. This study will complement the two ongoing Phase 2 studies, VLA15-201 (initial positive data reported on 22nd July 2020) and VLA15-202 (initial positive data reported on 20th October 2020).

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 were 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.

October 20, 2020 – Valneva SE announced positive initial results for its second Phase 2 study (VLA15-202) of Lyme disease vaccine candidate VLA15.

September 28, 2021 – Valneva SE and Pfizer Inc. announced further positive Phase 2 results, including booster response, for Lyme disease vaccine candidate VLA15.

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.

Clinical Trials