RSV-MVA-BN Vaccine Phase II Trial in ≥ 55 Year Old Adults

Study Overview
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Brief Summary
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A total of 400 subjects will be recruited into five treatment subject groups à 80 subjects.Subject will receive two administrations 4 weeks apart which will consist of MVA-BN-RSV Dose 1, MVA-BN-RSV Dose 2 or Placebo (TBS). 86 subjects from 2 treatment groups (43 per treatment group) are supposed to receive one (booster) dose of MVA-BN-RSV vaccine approximately one year after their first vaccination. In this booster substudy, eligible subjects will receive the same dose they received during the main trial.

Official Title
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A Randomized, Single-blind, Placebo Controlled, Dose-ranging Phase II Trial in ≥ 55 Year Old Adults to Evaluate the Safety and Immunogenicity of the Recombinant MVA-BN-RSV Vaccine

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Biological: MVA-BN-RSV
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Main study): Male and female subjects, ≥ 55 years of age. Prior to performance of any trial specific procedures, the subject has read, signed and dated an informed consent form, having been advised of the risks and benefits of the trial in a language understood by the subject, and has signed the Health Insurance Portability and Accountability Act (HIPAA) authorization form. Subjects without symptomatic cardiopulmonary and/or metabolic disease. Note that subjects who have any active symptoms related to cardiac and/or pulmonary and/or metabolic disease (including e.g. uncontrolled asthma, angina pectoris, hyperglycaemia or other episodic symptoms), or who receive ongoing therapy to control current, active symptoms, are not eligible. Subjects on stable treatment (no change in ≥ 1 month) for previous and controlled symptoms or conditions are eligible. The following are examples of subjects who may bear cardiopulmonary or metabolic diagnoses but who would remain eligible: Subjects on stable (no change in ≥ 1 month) therapy for findings (e.g. hypertension, hyperlipidemia) which are not associated with current symptoms or disability. Subjects with type II diabetes mellitus are considered eligible as long as they are stable on oral antidiabetics and have either a documented glycated hemoglobin (HbA1c) of ≤ 8 % within three months prior to trial participation or confirmation of controlled blood glucose level must be obtained at the SCR (screening) visit by a lab test. Subjects who receive short term treatment for temporary conditions. Other clinically insignificant findings not deemed to be associated with increased risk for respiratory viral infections as determined by the investigator. Able to comply with trial requirements; including access to transportation for trial visits. Body mass index (BMI) ≥ 18.5 and ≤ 39.9 BMI formula for pounds and inches: BMI = (bodyweight in pounds) * 703 (bodyheight in inches)2 Women of childbearing potential (WOCBP) must have used an acceptable method of contraception for at least 30 days prior to the first vaccination, must agree to use an acceptable method of contraception (as defined in Section 8.2.11) during the trial, and must avoid becoming pregnant for at least 28 days after the last vaccination. WOCBP must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to each vaccination Not clinically significant laboratory values as defined in the protocol, excluding any Grade ≥ 3 toxicity. Negative human immunodeficiency virus antibody test (anti-HIV), negative hepatitis B surface antigen (HBsAG) and negative antibody test to hepatitis C virus. Electrocardiogram (ECG) without clinically significant acute findings (e.g. findings suggestive of current ischemia, ventricular arrhythmias, congestive heart failure and ventricular hypertrophy). Exclusion Criteria (Main Study): Pregnant or breast-feeding women. Uncontrolled serious infection, i.e. not responding to antimicrobial therapy. History or current clinical manifestation of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject or would limit the subject's ability to complete the trial. History of cerebrovascular disorders, including stroke. Patients with history of transient ischaemic attack (TIA) ≥ 1 year prior to trial participation remain eligible. History of myocardial infarction within ≤ 1 year prior to trial participation, current clinical manifestation of angina pectoris, current clinical manifestation of congestive heart failure ≥ New York Heart Association (NYHA) Grade II, uncontrolled high blood pressure defined as systolic blood pressure ≥ 150 mmHg and/or diastolic ≥ 100 mmHg within the last 2 months. History of or active autoimmune disease. Persons with vitiligo or thyroid disease taking thyroid replacement are not excluded. Persons with rheumatoid arthritis not requiring immunomodulatory and/or immunosuppressant treatment are not excluded. Known or suspected impairment of immunologic functions including, but not limited to chronic inflammatory bowel disorders, diabetes mellitus type I. History of malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision at least 6 months ago that is considered to have achieved cure. Subjects with history of skin cancer should not be vaccinated at the previous tumor site. Clinically significant mental disorder, not adequately controlled by medical treatment. Active or recent (within the time period of six months before trial participation) history of chronic alcohol abuse and/or intravenous and/or nasal drug abuse. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. tris(hydroxymethyl)-amino methane, chicken embryo fibroblast proteins, gentamycin. Known allergy to eggs or aminoglycosides. History of anaphylaxis or severe allergic reaction to any vaccine. Having received any vaccinations or planned vaccinations with a live vaccine within 30 days prior to or after trial vaccination. Having received any vaccinations or planned vaccinations with an inactivated vaccine within 14 days prior to or after trial vaccination. Chronic systemic administration (defined as more than 14 days) of > 5 mg prednisone (or equivalent)/day or any other immune-modifying drugs during a period starting from three months prior to first administration of the trial vaccination and ending at the last visit of the active trial phase. The use of topical, inhaled, ophthalmic and nasal glucocorticoids is permitted. Administration or planned administration of immunoglobulins and/or any blood products during a period starting from three months prior to first administration of the trial vaccination and ending at the last visit of the active trial phase. Use of any investigational or non-registered drug or vaccine other than the trial vaccine within 30 days preceding the first trial vaccination, or planned administration of such a drug between participation in the trial and until 4 weeks after last trial vaccination. Previous or planned vaccination with a RSV vaccine/vaccine candidate. Clinical trial personnel working on the current trial. Inclusion Criteria (Substudy): Prior to performance of any booster substudy specific procedures, the subject has read, signed and dated an informed consent form, having been advised of the risks and benefits of the trial in a language understood by the subject. Subject has completed all vaccinations of the main trial according to protocol. Exclusion Criteria (Substudy): Any condition that, in the opinion of the investigator, makes it unsafe for the subject to receive a further vaccination. Pregnancy. An anaphylactic reaction following the administration of any vaccine(s). Clinical need for concomitant or ancillary therapy not permitted in the trial as outlined in Protocol Section 8.2.2. Having received any vaccinations or planned vaccinations with a live vaccine within 30 days prior to or after booster vaccination. Having received any vaccinations or planned vaccinations with an inactivated vaccine within 14 days prior to or after booster vaccination. Chronic systemic administration (defined as more than 14 days) of > 5 mg prednisone (or equivalent)/day or any other immune-modifying drugs during a period starting from 3 months prior to administration of the booster vaccine and ending at the last visit of the booster active trial phase. The use of topical, inhaled, ophthalmic and nasal glucocorticoids is permitted. Administration or planned administration of immunoglobulins and/or any blood products during a period starting from 3 months prior to administration of the booster vaccine and ending at the last visit of the booster active trial phase. Use of any investigational or non-registered drug or vaccine other than the trial vaccine within 30 days preceding the booster vaccination, or planned administration of such a drug during participation in the booster substudy and until 4 weeks after booster vaccination. Subject's request to discontinue Subject's refusal to receive booster vaccination. Subject unwilling or unable to comply with trial requirements. Any reason that, in the opinion of the investigator contradicts administration of the booster vaccination or otherwise requires early discontinuation of a subject.

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 - Single Low Dose / Booster<br>First dose (Week 0): MVA-BN-RSV 1x10E8 Inf.U; Second dose (Week 4): placebo; Booster dose (Week 56): MVA-BN-RSV 1x10E8 Inf.U; (intramuscular vaccinations) | Biological: MVA-BN-RSV<br>* MVA-mBN294B<br>Other: Placebo<br>* Tris Buffered Saline, sterile<br>|
| Experimental: Group 2 - Two Low Doses<br>First dose (Week 0): MVA-BN-RSV 1x10E8 Inf.U; Second dose (Week 4): MVA-BN-RSV 1x10E8 Inf.U; (intramuscular vaccinations) | Biological: MVA-BN-RSV<br>* MVA-mBN294B<br>|
| Experimental: Group 3 - Single High Dose / Booster<br>First dose (Week 0): MVA-BN-RSV 5x10E8 Inf.U; Second dose (Week 4): placebo; Booster dose (Week 56): MVA-BN-RSV 5x10E8 Inf.U; (intramuscular vaccinations) | Biological: MVA-BN-RSV<br>* MVA-mBN294B<br>Other: Placebo<br>* Tris Buffered Saline, sterile<br>|
| Experimental: Group 4 - Two High Doses<br>First dose (Week 0): MVA-BN-RSV 5x10E8 Inf.U; Second dose (Week 4): MVA-BN-RSV 5x10E8 Inf.U; (intramuscular vaccinations) | Biological: MVA-BN-RSV<br>* MVA-mBN294B<br>|
| Experimental: Group 5 - Placebo<br>First dose (Week 0): placebo; Second dose (Week 4): placebo; (intramuscular vaccinations) | Other: Placebo<br>* Tris Buffered Saline, sterile<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PRNT (Subtype A) GMT | Geometric Mean Titers (GMTs) based on RSV-specific Plaque Reduction Neutralization Test (PRNT; against subtype A). Titers below the detection limit (DL) are included with a value of '10' (i.e. 1/2 DL) | Week 6 (Main Study) i.e., 2 weeks following the second vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PRNT (Subtype A) GMT | Geometric Mean Titers (GMTs) based on RSV-specific Plaque Reduction Neutralization Test (PRNT; against subtype A). Individual peak is defined as the maximum post-Baseline antibody titer up to the end of the respective active trial phase i.e., within 8 weeks for the main study and within 4 weeks for the booster substudy. Titers below the detection limit (DL) are included with a value of '10' (i.e. 1/2 DL) | within 108 weeks | 
| Percentage of Participants With Response by PRNT (Subtype A) | Response rate based on RSV-specific Plaque Reduction Neutralization Test (PRNT; against subtype A). Response is defined as the appearance of antibody titers ≥ detection limit (20) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Response for main study visits is based on main study Baseline, whereas response for booster study visits is based on booster substudy Baseline. Individual peak response rate is based on the maximum post-Baseline antibody titer up to the end of the respective active trial phase i.e., within 8 weeks for the main study and within 4 weeks for the booster substudy. Percentages based on number of subjects with data available. | within 108 weeks | 
| PRNT (Subtype B) GMT | Geometric Mean Titers (GMTs) based on RSV-specific Plaque Reduction Neutralization Test (PRNT; against subtype B). Individual peak is defined as the maximum post-Baseline antibody titer up to the end of the respective active trial phase i.e., within 8 weeks for the main study and within 4 weeks for the booster substudy. Titers below the detection limit (DL) are included with a value of '10' (i.e. 1/2 DL) | within 108 weeks | 
| Percentage of Participants With Response by PRNT (Subtype B) | Response rate based on RSV-specific Plaque Reduction Neutralization Test (PRNT; against subtype B). Response is defined as the appearance of antibody titers ≥ detection limit (20) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Response for main study visits is based on main study Baseline, whereas response for booster study visits is based on booster substudy Baseline. Individual peak response rate is based on the maximum post-Baseline antibody titer up to the end of the respective active trial phase i.e., within 8 weeks for the main study and within 4 weeks for the booster substudy. Percentages based on number of subjects with data available. | within 108 weeks | 
| ELISA (IgG) GMT | Geometric Mean Titers (GMTs) based on RSV-specific Immunoglobulin G (IgG) Enzyme-linked Immunosorbent Assay (ELISA). Individual peak is defined as the maximum post-Baseline antibody titer up to the end of the respective active trial phase i.e., within 8 weeks for the main study and within 4 weeks for the booster substudy. Titers below the detection limit (DL) are included with a value of '31.5' (i.e. 1/2 DL) | within 108 weeks | 
| Percentage of Participants With Response by IgG ELISA | Response rate based on RSV-specific Immunoglobulin G (IgG) Enzyme-linked Immunosorbent Assay (ELISA). Response is defined as the appearance of antibody titers ≥ detection limit (63) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Response for main study visits is based on main study Baseline, whereas response for booster study visits is based on booster substudy Baseline. Individual peak response rate is based on the maximum post-Baseline antibody titer up to the end of the respective active trial phase i.e., within 8 weeks for the main study and within 4 weeks for the booster substudy. Percentages based on number of subjects with data available. | within 108 weeks | 
| ELISA (IgA) GMT | Geometric Mean Titers (GMTs) based on RSV-specific Immunoglobulin A (IgA) Enzyme-linked Immunosorbent Assay (ELISA). Individual peak is defined as the maximum post-Baseline antibody titer up to the end of the respective active trial phase i.e., within 8 weeks for the main study and within 4 weeks for the booster substudy. Titers below the detection limit (DL) are included with a value of '50' (i.e. 1/2 DL) | within 108 weeks | 
| Percentage of Participants With Response by IgA ELISA | Response rate based on RSV-specific Immunoglobulin A (IgA) Enzyme-linked Immunosorbent Assay (ELISA). Response is defined as the appearance of antibody titers ≥ detection limit (100) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Response for main study visits is based on main study Baseline, whereas response for booster study visits is based on booster substudy Baseline. Individual peak response rate is based on the maximum post-Baseline antibody titer up to the end of the respective active trial phase i.e., within 8 weeks for the main study and within 4 weeks for the booster substudy. Percentages based on number of subjects with data available. | within 108 weeks | 
| ELISA (Mucosal IgA) GMT | Geometric Mean Titers (GMTs) based on mucosal RSV-specific Immunoglobulin A (IgA) Enzyme-linked Immunosorbent Assay (ELISA). Individual peak is defined as the maximum post-Baseline antibody titer up to the end of the respective active trial phase i.e., within 8 weeks for the main study and within 4 weeks for the booster substudy. Titers below the detection limit (DL) are included with a value of '1' (i.e. 1/2 DL) | within 82 weeks | 
| Percentage of Participants With Response by Mucosal IgA ELISA | Response rate based on mucosal RSV-specific Immunoglobulin A (IgA) Enzyme-linked Immunosorbent Assay (ELISA). Response is defined as the appearance of antibody titers ≥ detection limit (2) for initially negative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially positive subjects. Response for main study visits is based on main study Baseline, whereas response for booster study visits is based on booster substudy Baseline. Individual peak response rate is based on the maximum post-Baseline antibody titer up to the end of the respective active trial phase i.e., within 8 weeks for the main study and within 4 weeks for the booster substudy. Percentages based on number of subjects with data available. | within 82 weeks | 
| ELISPOT (IFN-g, Peptide Pool: F) GMSFU | Geometric Mean Spot Forming Units (GMSFUs) based on RSV-specific Interferon-gamma (IFN-g) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool F. Values below the detection limit (DL) are included with a value of '25' (i.e. 1/2 DL) | within 58 weeks | 
| ELISPOT (IFN-g, Peptide Pool: G(A)) GMSFU | Geometric Mean Spot Forming Units (GMSFUs) based on RSV-specific Interferon-gamma (IFN-g) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool G(A). Values below the detection limit (DL) are included with a value of '25' (i.e. 1/2 DL) | within 58 weeks | 
| ELISPOT (IFN-g, Peptide Pool: G(B)) GMSFU | Geometric Mean Spot Forming Units (GMSFUs) based on RSV-specific Interferon-gamma (IFN-g) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool G(B). Values below the detection limit (DL) are included with a value of '25' (i.e. 1/2 DL) | within 58 weeks | 
| ELISPOT (IFN-g, Peptide Pool: M2) GMSFU | Geometric Mean Spot Forming Units (GMSFUs) based on RSV-specific Interferon-gamma (IFN-g) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool M2. Values below the detection limit (DL) are included with a value of '25' (i.e. 1/2 DL) | within 58 weeks | 
| ELISPOT (IFN-g, Peptide Pool: N) GMSFU | Geometric Mean Spot Forming Units (GMSFUs) based on RSV-specific Interferon-gamma (IFN-g) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool N. Values below the detection limit (DL) are included with a value of '25' (i.e. 1/2 DL) | within 58 weeks | 
| ELISPOT (IL-4, Peptide Pool: F) GMSFU | Geometric Mean Spot Forming Units (GMSFUs) based on RSV-specific Interleukin 4 (IL-4) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool F. Values below the detection limit (DL) are included with a value of '25' (i.e. 1/2 DL) | within 58 weeks | 
| ELISPOT (IL-4, Peptide Pool: G(A)) GMSFU | Geometric Mean Spot Forming Units (GMSFUs) based on RSV-specific Interleukin 4 (IL-4) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool G(A). Values below the detection limit (DL) are included with a value of '25' (i.e. 1/2 DL) | within 58 weeks | 
| ELISPOT (IL-4, Peptide Pool: G(B)) GMSFU | Geometric Mean Spot Forming Units (GMSFUs) based on RSV-specific Interleukin 4 (IL-4) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool G(B). Values below the detection limit (DL) are included with a value of '25' (i.e. 1/2 DL) | within 58 weeks | 
| ELISPOT (IL-4, Peptide Pool: M2) GMSFU | Geometric Mean Spot Forming Units (GMSFUs) based on RSV-specific Interleukin 4 (IL-4) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool M2. Values below the detection limit (DL) are included with a value of '25' (i.e. 1/2 DL) | within 58 weeks | 
| ELISPOT (IL-4, Peptide Pool: N) GMSFU | Geometric Mean Spot Forming Units (GMSFUs) based on RSV-specific Interleukin 4 (IL-4) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool N. Values below the detection limit (DL) are included with a value of '25' (i.e. 1/2 DL) | within 58 weeks | 
| Percentage of Participants With Response by ELISPOT (IFN-g, Peptide Pool: F) | Response rate based on RSV-specific Interferon-gamma (IFN-g) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool F. Response is defined as the appearance of spot forming units ≥ detection limit (50) for initially negative subjects, or a doubling or more of the spot forming units compared to Baseline for initially positive subjects. Response for main study visits is based on main study Baseline, whereas response for booster study visits is based on booster substudy Baseline. Percentages based on number of subjects with paired data available, i.e. number of subjects with results available for the respective time point and the corresponding Baseline. | within 58 weeks | 
| Percentage of Participants With Response by ELISPOT (IFN-g, Peptide Pool: G(A)) | Response rate based on RSV-specific Interferon-gamma (IFN-g) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool G(A). Response is defined as the appearance of spot forming units ≥ detection limit (50) for initially negative subjects, or a doubling or more of the spot forming units compared to Baseline for initially positive subjects. Response for main study visits is based on main study Baseline, whereas response for booster study visits is based on booster substudy Baseline. Percentages based on number of subjects with paired data available, i.e. number of subjects with results available for the respective time point and the corresponding Baseline. | within 58 weeks | 
| Percentage of Participants With Response by ELISPOT (IFN-g, Peptide Pool: G(B)) | Response rate based on RSV-specific Interferon-gamma (IFN-g) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool G(B). Response is defined as the appearance of spot forming units ≥ detection limit (50) for initially negative subjects, or a doubling or more of the spot forming units compared to Baseline for initially positive subjects. Response for main study visits is based on main study Baseline, whereas response for booster study visits is based on booster substudy Baseline. Percentages based on number of subjects with paired data available, i.e. number of subjects with results available for the respective time point and the corresponding Baseline. | within 58 weeks | 
| Percentage of Participants With Response by ELISPOT (IFN-g, Peptide Pool: M2) | Response rate based on RSV-specific Interferon-gamma (IFN-g) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool M2. Response is defined as the appearance of spot forming units ≥ detection limit (50) for initially negative subjects, or a doubling or more of the spot forming units compared to Baseline for initially positive subjects. Response for main study visits is based on main study Baseline, whereas response for booster study visits is based on booster substudy Baseline. Percentages based on number of subjects with paired data available, i.e. number of subjects with results available for the respective time point and the corresponding Baseline. | within 58 weeks | 
| Percentage of Participants With Response by ELISPOT (IFN-g, Peptide Pool: N) | Response rate based on RSV-specific Interferon-gamma (IFN-g) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool N. Response is defined as the appearance of spot forming units ≥ detection limit (50) for initially negative subjects, or a doubling or more of the spot forming units compared to Baseline for initially positive subjects. Response for main study visits is based on main study Baseline, whereas response for booster study visits is based on booster substudy Baseline. Percentages based on number of subjects with paired data available, i.e. number of subjects with results available for the respective time point and the corresponding Baseline. | within 58 weeks | 
| Percentage of Participants With Response by ELISPOT (IL-4, Peptide Pool: F) | Response rate based on RSV-specific Interleukin 4 (IL-4) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool F. Response is defined as the appearance of spot forming units ≥ detection limit (50) for initially negative subjects, or a doubling or more of the spot forming units compared to Baseline for initially positive subjects. Response for main study visits is based on main study Baseline, whereas response for booster study visits is based on booster substudy Baseline. Percentages based on number of subjects with paired data available, i.e. number of subjects with results available for the respective time point and the corresponding Baseline. | within 58 weeks | 
| Percentage of Participants With Response by ELISPOT (IL-4, Peptide Pool: G(A)) | Response rate based on RSV-specific Interleukin 4 (IL-4) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool G(A). Response is defined as the appearance of spot forming units ≥ detection limit (50) for initially negative subjects, or a doubling or more of the spot forming units compared to Baseline for initially positive subjects. Response for main study visits is based on main study Baseline, whereas response for booster study visits is based on booster substudy Baseline. Percentages based on number of subjects with paired data available, i.e. number of subjects with results available for the respective time point and the corresponding Baseline. | within 58 weeks | 
| Percentage of Participants With Response by ELISPOT (IL-4, Peptide Pool: G(B)) | Response rate based on RSV-specific Interleukin 4 (IL-4) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool G(B). Response is defined as the appearance of spot forming units ≥ detection limit (50) for initially negative subjects, or a doubling or more of the spot forming units compared to Baseline for initially positive subjects. Response for main study visits is based on main study Baseline, whereas response for booster study visits is based on booster substudy Baseline. Percentages based on number of subjects with paired data available, i.e. number of subjects with results available for the respective time point and the corresponding Baseline. | within 58 weeks | 
| Percentage of Participants With Response by ELISPOT (IL-4, Peptide Pool: M2) | Response rate based on RSV-specific Interleukin 4 (IL-4) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool M2. Response is defined as the appearance of spot forming units ≥ detection limit (50) for initially negative subjects, or a doubling or more of the spot forming units compared to Baseline for initially positive subjects. Response for main study visits is based on main study Baseline, whereas response for booster study visits is based on booster substudy Baseline. Percentages based on number of subjects with paired data available, i.e. number of subjects with results available for the respective time point and the corresponding Baseline. | within 58 weeks | 
| Percentage of Participants With Response by ELISPOT (IL-4, Peptide Pool: N) | Response rate based on RSV-specific Interleukin 4 (IL-4) Enzyme-linked Immuno Spot Technique (ELISPOT) for the Peptide Pool N. Response is defined as the appearance of spot forming units ≥ detection limit (50) for initially negative subjects, or a doubling or more of the spot forming units compared to Baseline for initially positive subjects. Response for main study visits is based on main study Baseline, whereas response for booster study visits is based on booster substudy Baseline. Percentages based on number of subjects with paired data available, i.e. number of subjects with results available for the respective time point and the corresponding Baseline. | within 58 weeks | 
| Memory B Cells (IgG) GMSFU | Geometric Mean Spot Forming Units (GMSFUs) based on RSV-specific Immunoglobulin G (IgG)-producing memory B cells. Negative results (i.e. results below 0.01) are included with a value of '0.005' | within 82 weeks | 
| Serious Adverse Events | Number of participants reporting Serious Adverse Events per period: Between 1st and 2nd vaccination (Vaccination Period 1, Main Study, duration: 4 weeks), between 2nd vaccination and end of active phase of the Main Study (Vaccination Period 2, Main Study, duration: 4 weeks), during the follow-up phase of the Main Study (Follow-Up, Main Study, duration: 22 weeks), after the Main Study and before the booster vaccination (Between Study Parts [retrospectively collected in booster substudy], duration: 26 weeks), between booster vaccination and end of active phase of the Booster Substudy (Booster Vaccination Period, Booster Substudy, duration: 4 weeks), and during the follow-up phase of the Booster Substudy (Follow-Up, Booster Substudy, duration: 48 weeks). Percentages based on number of subjects still in the study at the start of the respective period. | within 108 weeks (Main Study + Booster Substudy) | 
| Related Serious Adverse Events | Number of participants reporting Serious Adverse Events possibly, probably or definitely related to the trial vaccine per period: Between 1st and 2nd vaccination (Vaccination Period 1, Main Study, duration: 4 weeks), between 2nd vaccination and end of active phase of the Main Study (Vaccination Period 2, Main Study, duration: 4 weeks), during the follow-up phase of the Main Study (Follow-Up, Main Study, duration: 22 weeks), after the Main Study and before the booster vaccination (Between Study Parts [retrospectively collected in booster substudy], duration: 26 weeks), between booster vaccination and end of active phase of the Booster Substudy (Booster Vaccination Period, Booster Substudy, duration: 4 weeks), and during the follow-up phase of the Booster Substudy (Follow-Up, Booster Substudy, duration: 48 weeks). Percentages based on number of subjects still in the study at the start of the respective period. | within 108 weeks (Main Study + Booster Substudy) | 
| Grade ≥ 3 Serious Adverse Events | Number of participants reporting Serious Adverse Events with intensity ≥ Grade 3 per period: Between 1st and 2nd vaccination (Vaccination Period 1, Main Study, duration: 4 weeks), between 2nd vaccination and end of active phase of the Main Study (Vaccination Period 2, Main Study, duration: 4 weeks), during the follow-up phase of the Main Study (Follow-Up, Main Study, duration: 22 weeks), after the Main Study and before the booster vaccination (Between Study Parts [retrospectively collected in booster substudy], duration: 26 weeks), between booster vaccination and end of active phase of the Booster Substudy (Booster Vaccination Period, Booster Substudy, duration: 4 weeks), and during the follow-up phase of the Booster Substudy (Follow-Up, Booster Substudy, duration: 48 weeks). Percentages based on number of subjects still in the study at the start of the respective period. | within 108 weeks (Main Study + Booster Substudy) | 
| Related Grade ≥ 3 Adverse Events | Number of participants reporting Adverse Events possibly, probably or definitely related to the trial vaccine with intensity ≥ Grade 3 per period: Following the 1st vaccination (Vaccination Period 1, Main Study), following the 2nd vaccination (Vaccination Period 2, Main Study), and following the booster vaccination (Booster Vaccination Period, Booster Substudy). Pooled solicited (general only) and unsolicited AEs. Percentages based on number of subjects still in the study at the start of the respective period. | within 29 days after vaccination | 
| Solicited Local Adverse Events | Incidence of injection site reactions (solicited via diary cards) after vaccination: Following the 1st vaccination (Vaccination Period 1, Main Study), following the 2nd vaccination (Vaccination Period 2, Main Study), and following the booster vaccination (Booster Vaccination Period, Booster Substudy). Percentages based on number of subjects with a completed diary card for the respective vaccination period. | within 8 days after vaccination | 
| Grade ≥ 3 Solicited Local Adverse Events | Incidence of injection site reactions (solicited via diary cards) with intensity ≥ Grade 3 after vaccination: Following the 1st vaccination (Vaccination Period 1, Main Study), following the 2nd vaccination (Vaccination Period 2, Main Study), and following the booster vaccination (Booster Vaccination Period, Booster Substudy). Percentages based on number of subjects with a completed diary card for the respective vaccination period. | within 8 days after vaccination | 
| Solicited General Adverse Events | Incidence of systemic reactions (solicited via diary cards) after vaccination: Following the 1st vaccination (Vaccination Period 1, Main Study), following the 2nd vaccination (Vaccination Period 2, Main Study), and following the booster vaccination (Booster Vaccination Period, Booster Substudy). Percentages based on number of subjects with a completed diary card for the respective vaccination period. | within 8 days after vaccination | 
| Grade ≥ 3 Solicited General Adverse Events | Incidence of systemic reactions (solicited via diary cards) with intensity ≥ Grade 3 after vaccination: Following the 1st vaccination (Vaccination Period 1, Main Study), following the 2nd vaccination (Vaccination Period 2, Main Study), and following the booster vaccination (Booster Vaccination Period, Booster Substudy). Percentages based on number of subjects with a completed diary card for the respective vaccination period. | within 8 days after vaccination | 
| Related Solicited General Adverse Events | Incidence of systemic reactions (solicited via diary cards) possibly, probably or definitely related to the trial vaccine after vaccination: Following the 1st vaccination (Vaccination Period 1, Main Study), following the 2nd vaccination (Vaccination Period 2, Main Study), and following the booster vaccination (Booster Vaccination Period, Booster Substudy). Percentages based on number of subjects with a completed diary card for the respective vaccination period. | within 8 days after vaccination | 
| Unsolicited Non-serious Adverse Events | Incidence of unsolicited non-serious adverse events by period: Following the 1st vaccination (Vaccination Period 1, Main Study), following the 2nd vaccination (Vaccination Period 2, Main Study), and following the booster vaccination (Booster Vaccination Period, Booster Substudy). Percentages based on number of subjects having received the respective vaccination. | within 29 days after vaccination | 
| Related Unsolicited Non-serious Adverse Events | Incidence of unsolicited non-serious adverse events possibly, probably or definitely related to the trial vaccine by period: Following the 1st vaccination (Vaccination Period 1, Main Study), following the 2nd vaccination (Vaccination Period 2, Main Study), and following the booster vaccination (Booster Vaccination Period, Booster Substudy). Percentages based on number of subjects having received the respective vaccination. | within 29 days after vaccination | 
| Grade ≥ 3 Unsolicited Non-serious Adverse Events | Incidence of unsolicited non-serious adverse events with intensity ≥ Grade 3 by period: Following the 1st vaccination (Vaccination Period 1, Main Study), following the 2nd vaccination (Vaccination Period 2, Main Study), and following the booster vaccination (Booster Vaccination Period, Booster Substudy). Percentages based on number of subjects having received the respective vaccination. | within 29 days after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RSV Vaccines, Respiratory Syncytial Virus Vaccines