A Study to Evaluate the Safety and Immunogenicity of mRNA-1975 and mRNA-1982 Against Lyme Disease in Participants 18 Through 70 Years of Age

A Phase 1/2, Randomized, Observer-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Safety and Immunogenicity of Heptavalent mRNA-1975 (SR1-7) and Monovalent mRNA-1982 (SR1) in Parallel Against Lyme Disease in Healthy Participants 18 Through 70 Years of Age

The purpose of this study is to evaluate the safety and immunogenicity in parallel of heptavalent mRNA-1975 and monovalent mRNA-1982 against Lyme disease in healthy adult participants.

Study Overview

• Status: Completed
• Conditions: Lyme Disease
• Intervention / Treatment: Biological: mRNA-1975; Biological: mRNA-1982; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 807
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Milford, Connecticut, United States, 06460
      • Clinical Research Consulting, LLC
    • Stamford, Connecticut, United States, 06905
      • Stamford Therapeutics Consortium
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research, LLC
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Encore Research Group-Jacksonville Center for Clinical Research
    • Lake Mary, Florida, United States, 32746
      • University Clinical Research-DeLand, LLC d/b/a Accel Research Sites
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta, headlands LLC
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Johnson County Clin-Trials, Inc. (JCCT)
  • Maryland
    • Columbia, Maryland, United States, 21045
      • Centennial Medical Group
    • Rockville, Maryland, United States, 20850
      • Advanced Primary and Geriatric Care
  • Massachusetts
    • Brookline, Massachusetts, United States, 02445
      • DM Clinical Research - Brookline
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute, Inc.
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Meridian Clinical Research - Omaha
  • New Hampshire
    • Newington, New Hampshire, United States, 03801
      • ActivMed Research LLC
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
  • Pennsylvania
    • Hatboro, Pennsylvania, United States, 19040
      • Hatboro Medical Associates/CCT Research
  • Rhode Island
    • Providence, Rhode Island, United States, 02886
      • Velocity Clinical Research Providence
  • Texas
    • Fort Worth, Texas, United States, 76135
      • Benchmark Research
    • Tomball, Texas, United States, 77375
      • DM Clinical Research
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research Center, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body mass index of 18 to 39 kilograms/square meter (inclusive) at the Screening Visit.
• Participants of nonchildbearing potential may be enrolled in the study.
• For female participants of childbearing potential: negative pregnancy test, adequate contraception or has abstained from all activities that could result in pregnancy during the study intervention period, and agreement to continue adequate contraception or abstinence through 3 months following last study injection.

Exclusion Criteria:

• Have chronic illness related to Lyme disease or an active symptomatic Lyme disease infection as suspected or diagnosed by a physician.
• Received treatment for Lyme disease within the prior 3 months.
• Had previous vaccination against Lyme disease or participated in the past in any vaccine study for Lyme disease.
• Had a tick bite within 4 weeks prior to the study injection visit.
• Dermatologic conditions that could affect local solicited AR assessments (for example, tattoos; psoriasis patches affecting skin over the deltoid areas).
• Received systemic immunosuppressants for >14 days in total within 180 days prior to the Screening Visit (for corticosteroids, ≥10 milligrams/day of prednisone or equivalent) or is anticipating the need for systemic immunosuppressive treatment at any time during participation in the study.
• History of myocarditis, pericarditis, or myopericarditis regardless of the timing of past medical history.
• History of anaphylaxis, urticaria, or other significant adverse reaction requiring medical intervention after receipt of a vaccine or intervention that includes one or more of the same components contained in the study injection.
• Has received systemic immunoglobulins, long-acting biological therapies that affect immune responses (for example, infliximab) or blood products within 90 days prior to the Screening Visit or plans to receive them during the study.

Note: Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mRNA-1975: Dose 1; Participants will receive 3 intramuscular (IM) injections of the mRNA-1975 vaccine at Dose Level 1 on Days 1, 57, and 169.	Biological: mRNA-1975; Dispersion delivered IM; Other Names: SR1-7
Experimental: mRNA-1975: Dose 2; Participants will receive 3 IM injections of the mRNA-1975 vaccine at Dose level 2 on Days 1, 57, and 169.	Biological: mRNA-1975; Dispersion delivered IM; Other Names: SR1-7
Experimental: mRNA-1975: Dose 3; Participants will receive 3 IM injections of the mRNA-1975 vaccine at Dose Level 3 on Days 1, 57, and 169.	Biological: mRNA-1975; Dispersion delivered IM; Other Names: SR1-7
Experimental: mRNA-1975: Dose 4; Participants will receive 3 IM injections of the mRNA-1975 vaccine at Dose level 4 on Days 1, 57, and 169.	Biological: mRNA-1975; Dispersion delivered IM; Other Names: SR1-7
Experimental: mRNA-1982: Dose 1; Participants will receive 3 IM injections of the mRNA-1982 vaccine at Dose Level 1 on Days 1, 57, and 169.	Biological: mRNA-1982; Dispersion delivered IM; Other Names: SR1
Experimental: mRNA-1982: Dose 2; Participants will receive 3 IM injections of the mRNA-1982 vaccine at Dose Level 2 on Days 1, 57, and 169.	Biological: mRNA-1982; Dispersion delivered IM; Other Names: SR1
Experimental: mRNA-1982: Dose 3; Participants will receive 3 IM injections of the mRNA-1982 vaccine at Dose level 3 on Days 1, 57, and 169.	Biological: mRNA-1982; Dispersion delivered IM; Other Names: SR1
Placebo Comparator: Placebo; Participants will receive 3 IM injections of vaccine-matching placebo on Days 1, 57, and 169.	Biological: Placebo; Solution delivered IM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) Within 7 Days After Day 1 Injection	Solicited ARs were collected in an electronic diary (eDiary). Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered adverse events (AEs). Investigator reviewed whether the solicited AR was also to be recorded as an AE. A summary of serious AEs (SAEs) and nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.	Up to 7 days after Day 1 injection
Number of Participants With Solicited Local and Systemic ARs Within 7 Days After Day 57 Injection	Solicited ARs were collected in an eDiary. Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered AEs. Investigator reviewed whether the solicited AR was also to be recorded as an AE. A summary of SAEs and nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.	Up to 7 days after Day 57 injection
Number of Participants With Solicited Local and Systemic ARs Within 7 Days After Day 169 Injection	Solicited ARs were collected in an eDiary. Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered AEs. Investigator reviewed whether the solicited AR was also to be recorded as an AE. A summary of SAEs and nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.	Up to 7 days after Day 169 injection
Number of Participants With Unsolicited AEs	An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Any abnormal laboratory test result (hematology, clinical chemistry, or prothrombin time [PT]/partial thromboplastin time [PTT]) or other safety assessment (for example, electrocardiogram, radiological scan, vital sign measurement), including one that worsened from baseline and was considered clinically significant in the medical and scientific judgment of the Investigator was recorded as an AE. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.	Up to 28 days post any injection
Number of Participants With Medically Attended AEs (MAAEs), Adverse Events of Special Interest (AESIs), SAEs, and AEs Leading to Study Discontinuation	A MAAE is an AE that led to an unscheduled visit to a healthcare practitioner. An SAE was defined as any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability, was a congenital anomaly/birth defect, or was an important medical event. An AESI was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor were required. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.	Day 1 up to Month 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Concentration (GMC) of Anti-Outer Surface Protein (Anti-OspA) Binding Immunoglobulin (IgG) Antibodies for Serotype (SR-1) Antigen Measured by Enzyme-Linked Immunosorbent Assay (ELISA)	Antibody values reported as below lower limit of quantification (LLOQ) were replaced by 0.5*LLOQ. Values reported greater than upper limit of quantification (ULOQ) were replaced by the ULOQ. LLOQ was 41.4 nanograms (ng)/milliliter (mL) and ULOQ was 428000 ng/mL for manual assay; LLOQ was 47.6 ng/mL and 583000 ng/mL for automated assay for SR-1 IgG antibody. 95% confidence interval (CI) for GM value was calculated based on the t-distribution of the log-transformed values , then back transformed to the original scale for presentation.	Days 1, 29, 85 and 197
GMC of Anti-OspA Binding IgG Antibodies for SR-2 Antigen Measured by ELISA	Antibody values reported as below LLOQ were replaced by 0.5*LLOQ. Values reported greater than ULOQ were replaced by the ULOQ. LLOQ was 30 ng/mL and ULOQ was 214000 ng/mL for manual assay; LLOQ was 66.6 ng/mL and 215000 ng/mL for automated assay for SR-2 IgG antibody. 95% CI for GM value was calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation. Since mRNA-1982 was designed to elicit antibodies against SR-1 antigen only, the data for this outcome measure has been reported for mRNA-1975 and placebo arms only.	Days 1, 29, 85, and 197
GMC of Anti-OspA Binding IgG Antibodies for SR-3 Antigen Measured by ELISA	Antibody values reported as below LLOQ were replaced by 0.5*LLOQ. Values reported greater than ULOQ were replaced by the ULOQ. LLOQ was 14.5 ng/mL and ULOQ was 299000 ng/mL for manual assay; LLOQ was 62.5 ng/mL and 296000 ng/mL for automated assay for SR-3 IgG antibody. 95% CI for GM value was calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation. Since mRNA-1982 was designed to elicit antibodies against SR-1 antigen only, the data for this outcome measure has been reported for mRNA-1975 and placebo arms only.	Days 1, 29, 85 and 197
GMC of Anti-OspA Binding IgG Antibodies for SR-4 Antigen Measured by ELISA	Antibody values reported as below LLOQ were replaced by 0.5*LLOQ. Values reported greater than ULOQ were replaced by the ULOQ. LLOQ was 32.6 ng/mL and ULOQ was 292000 ng/mL for manual assay; LLOQ was 59.7 ng/mL and 264000 ng/mL for automated assay for SR-4 IgG antibody. 95% CI for GM value was calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation. Since mRNA-1982 was designed to elicit antibodies against SR-1 antigen only, the data for this outcome measure has been reported for mRNA-1975 and placebo arms only.	Days 1, 29, 85 and 197
GMC of Anti-OspA Binding IgG Antibodies for SR-5 Antigen Measured by ELISA	Antibody values reported as below LLOQ were replaced by 0.5*LLOQ. Values reported greater than ULOQ were replaced by the ULOQ. LLOQ was 45.5 ng/mL and ULOQ was 298000 ng/mL for manual assay; LLOQ was 84.2 ng/mL and 319000 ng/mL for automated assay for SR-5 IgG antibody. 95% CI for GM value was calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation. Since mRNA-1982 was designed to elicit antibodies against SR-1 antigen only, the data for this outcome measure has been reported for mRNA-1975 and placebo arms only.	Days 1, 29, 85 and 197
GMC of Anti-OspA Binding IgG Antibodies for SR-6 Antigen Measured by ELISA	Antibody values reported as below LLOQ were replaced by 0.5*LLOQ. Values reported greater than ULOQ were replaced by the ULOQ. LLOQ was 18.1 ng/mL and ULOQ was 203000 ng/mL for manual assay; LLOQ was 68.7 ng/mL and 248000 ng/mL for automated assay for SR-6 IgG antibody. 95% CI for GM value was calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation. Since mRNA-1982 was designed to elicit antibodies against SR-1 antigen only, the data for this outcome measure has been reported for mRNA-1975 and placebo arms only.	Days 1, 29, 85 and 197
GMC of Anti-OspA Binding IgG Antibodies for SR-7 Antigen Measured by ELISA	Antibody values reported as below LLOQ were replaced by 0.5*LLOQ. Values reported greater than ULOQ were replaced by the ULOQ. LLOQ was 13 ng/mL and ULOQ was 197000 ng/mL for manual assay; LLOQ was 78.9 ng/mL and 174000 ng/mL for automated assay for SR-7 IgG antibody. 95% CI for GM value was calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation. Since mRNA-1982 was designed to elicit antibodies against SR-1 antigen only, the data for this outcome measure has been reported for mRNA-1975 and placebo arms only.	Days 1, 29, 85 and 197
Geometric Mean Fold Rise (GMFR) of Anti-OspA Binding IgG Antibody Concentration for SR-1 Antigen	Antibody values reported as below LLOQ were replaced by 0.5*LLOQ. Values reported greater than ULOQ were replaced by the ULOQ. LLOQ was 41.4 ng/mL and ULOQ was 428000 ng/mL for manual assay; LLOQ was 47.6 ng/mL and 583000 ng/mL for automated assay for SR-1 IgG antibody. 95% CI for GMFR value was calculated based on the t-distribution of the difference in the log-transformed values, then back transformed to the original scale for presentation.	Days 29, 85 and 197
GMFR of Anti-OspA Binding IgG Antibody Concentration for SR-2 Antigen	Antibody values reported as below LLOQ were replaced by 0.5*LLOQ. Values reported greater than ULOQ were replaced by the ULOQ. LLOQ was 30 ng/mL and ULOQ was 214000 ng/mL for manual assay; LLOQ was 66.6 ng/mL and 215000 ng/mL for automated assay for SR-2 IgG antibody. 95% CI for GMFR value was calculated based on the t-distribution of the difference in the log-transformed values, then back transformed to the original scale for presentation. Since mRNA-1982 was designed to elicit antibodies against SR-1 antigen only, the data for this outcome measure has been reported for mRNA-1975 and placebo arms only.	Days 29, 85 and 197
GMFR of Anti-OspA Binding IgG Antibody Concentration for SR-3 Antigen	Antibody values reported as below LLOQ were replaced by 0.5*LLOQ. Values reported greater than ULOQ were replaced by the ULOQ. LLOQ was 14.5 ng/mL and ULOQ was 299000 ng/mL for manual assay; LLOQ was 62.5 ng/mL and 296000 ng/mL for automated assay for SR-3 IgG antibody. 95% CI for GMFR value was calculated based on the t-distribution of the difference in the log-transformed values, then back transformed to the original scale for presentation. Since mRNA-1982 was designed to elicit antibodies against SR-1 antigen only, the data for this outcome measure has been reported for mRNA-1975 and placebo arms only.	Days 29, 85 and 197
GMFR of Anti-OspA Binding IgG Antibody Concentration for SR-4 Antigen	Antibody values reported as below LLOQ were replaced by 0.5*LLOQ. Values reported greater than ULOQ were replaced by the ULOQ. LLOQ was 32.6 ng/mL and ULOQ was 292000 ng/mL for manual assay; LLOQ was 59.7 ng/mL and 264000 ng/mL for automated assay for SR-4 IgG antibody. 95% CI for GMFR value was calculated based on the t-distribution of the difference in the log-transformed values, then back transformed to the original scale for presentation. Since mRNA-1982 was designed to elicit antibodies against SR-1 antigen only, the data for this outcome measure has been reported for mRNA-1975 and placebo arms only.	Days 29, 85 and 197
GMFR of Anti-OspA Binding IgG Antibody Concentration for SR-5 Antigen	Antibody values reported as below LLOQ were replaced by 0.5*LLOQ. Values reported greater than ULOQ were replaced by the ULOQ. LLOQ was 45.5 ng/mL and ULOQ was 298000 ng/mL for manual assay; LLOQ was 84.2 ng/mL and 319000 ng/mL for automated assay for SR-5 IgG antibody. 95% CI for GMFR value was calculated based on the t-distribution of the difference in the log-transformed values, then back transformed to the original scale for presentation. Since mRNA-1982 was designed to elicit antibodies against SR-1 antigen only, the data for this outcome measure has been reported for mRNA-1975 and placebo arms only.	Days 29, 85 and 197
GMFR of Anti-OspA Binding IgG Antibody Concentration for SR-6 Antigen	Antibody values reported as below LLOQ were replaced by 0.5*LLOQ. Values reported greater than ULOQ were replaced by the ULOQ. LLOQ was 18.1 ng/mL and ULOQ was 203000 ng/mL for manual assay; LLOQ was 68.7 ng/mL and 248000 ng/mL for automated assay for SR-6 IgG antibody. 95% CI for GMFR value was calculated based on the t-distribution of the difference in the log-transformed values, then back transformed to the original scale for presentation. Since mRNA-1982 was designed to elicit antibodies against SR-1 antigen only, the data for this outcome measure has been reported for mRNA-1975 and placebo arms only.	Days 29, 85 and 197
GMFR of Anti-OspA Binding IgG Antibody Concentration for SR-7 Antigen	Antibody values reported as below LLOQ were replaced by 0.5*LLOQ. Values reported greater than ULOQ were replaced by the ULOQ. LLOQ was 13 ng/mL and ULOQ was 197000 ng/mL for manual assay; LLOQ was 78.9 ng/mL and 174000 ng/mL for automated assay for SR-7 IgG antibody. 95% CI for GMFR value was calculated based on the t-distribution of the difference in the log-transformed values, then back transformed to the original scale for presentation. Since mRNA-1982 was designed to elicit antibodies against SR-1 antigen only, the data for this outcome measure has been reported for mRNA-1975 and placebo arms only.	Days 29, 85 and 197

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Deaths Related to Study Drug	A death that occurred during the study or that came to the attention of the investigator during the study was reported to the Sponsor, whether or not it was considered related to study drug. The investigator assessed causality (that is, whether there is a reasonable possibility that the study drug caused the death). The relationship was characterized using the following classifications: Not related: There was not a reasonable possibility of a relationship to the study drug. The temporal sequence of the death relative to administration of the study drug was not reasonable AND/OR the death was more likely explained by a cause other than the study drug. Related: There was a reasonable possibility of a relationship to the study drug. There was evidence of exposure to the study drug. The temporal sequence of the death relative to the administration of the study drug was reasonable. The death was more likely explained by the study drug than by another cause.	Day 1 up to Month 18

Collaborators and Investigators

• Sponsor: ModernaTX, Inc.

Publications and helpful links

General Publications

• Finn MB, Willsey G, Piazza CL, Clendenen L, Shrestha M, You SS, Ma L, Dhingra Y, Laciak AR, Uggowitzer KA, Obiero JM, Freeman-Gallant G, Natarajan H, Green S, Pirayesh E, Lai YT, Himansu S, Carfi A, Hu LT, Mantis N, Plante O, Dold C. Monovalent and multivalent OspA mRNA-LNP vaccines elicit functional antibodies and protect against Borrelia burgdorferi in mice. NPJ Vaccines. 2026 May 5. doi: 10.1038/s41541-026-01451-7. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2023
• Primary Completion (Actual): May 30, 2025
• Study Completion (Actual): May 30, 2025

Study Registration Dates

• First Submitted: July 26, 2023
• First Submitted That Met QC Criteria: July 26, 2023
• First Posted (Actual): August 3, 2023

Study Record Updates

• Last Update Posted (Actual): July 30, 2026
• Last Update Submitted That Met QC Criteria: July 6, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Vaccine; Moderna; Messenger RNA; Lyme Disease Vaccine; mRNA-1975; mRNA-1982
• Additional Relevant MeSH Terms: Vector Borne Diseases; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Borrelia Infections; Spirochaetales Infections; Tick-Borne Diseases; Lyme Disease
• Other Study ID Numbers: mRNA-1975/1982-P101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No