Lyophilized shingles mRNA vaccine safety and immune response

A Randomized, Double-Blind, Controlled Phase I/II Clinical Trial to Evaluate the Safety and Immunogenicity of Different Doses of a Lyophilized Herpes Zoster Virus mRNA Vaccine in Adults Aged 40 Years and Older

This trial will test a lyophilized mRNA vaccine to see if it is safe and produces immune responses in adults aged 40 years and older.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 519 (estimated)
• Ages: 40 Years and up
• Sex: All
• Sponsor: Sinovac Biotech Co., Ltd (industry)
• Drugs / interventions: prednisone
• Locations: 1 site (Xinjiang)
• Trial ID: NCT07400003 on ClinicalTrials.gov

What this trial studies

The trial is a randomized, double-blind, controlled study conducted in two parts: Part A enrolled healthy adults aged 40 and older to examine safety and preliminary immune responses after two doses, and Part B enrolled adults aged 50 and older to identify the optimal dose and schedule. Participants were randomized to receive low- or high-dose experimental vaccine, an active comparator, or placebo with safety monitored throughout. Humoral and cellular immune responses were measured, and immune persistence was followed at multiple timepoints. The design included sequential enrollment by age and dose in Part A and multiple immunization schedules in Part B to support selection of a regimen for further development.

Who should consider this trial

Good fit: Healthy adults able to consent and comply with visits, aged 40 years or older for Phase I and 50 years or older for Phase II, who have no history of adult chickenpox or herpes zoster and agree to required contraception if applicable are the intended participants.

Not a fit: People with a history of chickenpox or herpes zoster in adulthood, prior varicella/zoster vaccination, or who cannot comply with study procedures are unlikely to benefit from participating.

Why it matters

Potential benefit: If successful, the vaccine could provide protection against shingles and, as a lyophilized product, may be easier to store and distribute than liquid mRNA formulations.

How similar studies have performed: mRNA vaccines have produced strong immune responses in other indications such as COVID-19, but lyophilized mRNA vaccines for herpes zoster are novel and have limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

* Phase I: Age ≥ 40 years; Phase II: Age ≥ 50 years;
* Participants are able to understand and voluntarily sign the informed consent form;
* Able to provide legal identification;
* Participants of childbearing potential and their sexual partners agree to voluntarily adopt effective contraceptive measures from the signing of the informed consent form until 6 months after the last dose of the investigational vaccine, with no plans for sperm or egg donation;
* Agree to comply with the visit schedule, sample collection, vaccination, and other trial procedures throughout the study period, and remain accessible at all times during the trial.

Exclusion Criteria:

* History of chickenpox or herpes zoster in adulthood;
* History of chickenpox or herpes zoster vaccination (including administration of registered products or participation in clinical trials of chickenpox or herpes zoster vaccines);
* Close contact with patients infected with chickenpox or herpes zoster within the past 30 days;
* Clinically significant abnormalities in protocol-specified clinical laboratory tests prior to vaccination (applicable to Phase I clinical trials only):

A. Hematological parameters: White blood cell count (WBC), hemoglobin (Hb), platelet count (Plt); B. Blood biochemical parameters: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), fasting blood glucose (Glu), creatinine (CR); C. Urinalysis parameter: Urine protein (PRO); D. Coagulation parameters: Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), international normalized ratio (INR); E. 12-lead electrocardiogram (ECG).

* Poorly controlled chronic diseases or significant medical history, including but not limited to cardiovascular diseases (e.g., poorly controlled hypertension defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg for participants aged 40-59 years prior to enrollment, or systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg for participants aged ≥60 years), metabolic disorders (e.g., poorly controlled diabetes), hematological diseases, hepatic or renal diseases, digestive system diseases, respiratory system diseases, history of major organ transplantation, or malignancy within the past five years;
* History of myocarditis, pericarditis, or idiopathic cardiomyopathy, or any condition that increases the risk of myocarditis or pericarditis;
* Autoimmune diseases, immunodeficiency diseases, or family history thereof (including but not limited to psoriasis, systemic lupus erythematosus, ankylosing spondylitis, autoimmune thyroid diseases, acute disseminated encephalomyelitis, facial paralysis, hypersensitivity reactions, polymyalgia rheumatica, rheumatoid arthritis, Guillain-Barré syndrome, asplenia, functional asplenia, HIV infection);
* Coagulation disorders (e.g., coagulation factor deficiencies, platelet abnormalities, or other coagulopathies);
* Current or previous severe neurological disorders (epilepsy, convulsions, or seizures) or psychiatric illnesses, or family history of psychiatric disorders;
* Acute illnesses or acute exacerbations of chronic diseases within the past 7 days, or known or suspected active infections;
* Immunosuppressive therapy or other immunomodulatory treatments (prednisone ≥20 mg/day or equivalent for \>14 days), cytotoxic therapy within the past 6 months, or planned use during the trial;
* Administration of immunoglobulins or other blood products within the past 3 months (use of hepatitis B immunoglobulin within the past 1 month), or planned use during the trial;
* Participation in other clinical studies within the past 30 days or planned participation during this trial;
* Vaccination with live-attenuated vaccines or nucleic acid vaccines within the past 28 days, or vaccination with subunit, inactivated, or other types of vaccines within the past 14 days;
* Known allergy to vaccines or vaccine components, such as urticaria, dyspnea, or angioedema following vaccination;
* Pregnancy, lactation, or positive urine pregnancy test in female participants;
* Fever (axillary temperature ≥37.3°C) within 3 days prior to vaccination or use of antipyretics, analgesics, or antihistamines (e.g., acetaminophen, ibuprofen, loratadine, cetirizine, etc.) as reported during inquiry;
* Physical examination deemed unsatisfactory on the day of planned vaccination;
* Skin lesions, inflammation, ulcers, rashes, scars, or other conditions at the target injection site that may interfere with administration or local reaction assessment;
* Any other factors deemed by the investigator to render the participant unsuitable for participation in the clinical trial.

Where this trial is running

Xinjiang

• Xinjiang Uygur Autonomous Region Center for Disease Control and Prevention — Xinjiang, China (RECRUITING)

Study contacts

• Principal investigator: Na Xie — Xinjiang Uygur Autonomous Region Center for Disease Control and Prevention
• Study coordinator: Na Xie

Conditions: Herpes Zoster, mRNA Vaccine