Study of the Safety and Immunogenicity of Reduced Doses of the US Yellow Fever Vaccine

March 20, 2026 updated by: US Army Medical Research Institute of Infectious Diseases

An Exploratory, Pilot Study of the Safety and Immunogenicity of Reduced Doses of the US Yellow Fever Vaccine

This is an open-label, randomized, exploratory study to evaluate the human immune response to reduced subcutaneous (SQ) dosing of Yellow Fever vaccine compared to the standard FDA approved subcutaneous vaccination dose. The current dose of the US FDA licensed Yellow Fever vaccine is approximately 55,000 plaque-forming unit(s) (PFU) in 0.5 mL administered SQ. Using the licensed dosage as standard, investigators are evaluating reduced doses of 1/5th (0.10 mL) and 1/10th (0.05 mL) standard Yellow Fever vaccine (YF-VAX).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Up to 150 individuals will be screened in order to randomize 90 eligible individuals to one of three groups: Group 1- YF-VAX® standard dose 0.5 mL SQ = 30 subjects; Group 2-0.10 mL (1/5th) SQ = 30 subjects; Group 3-0.05 mL (1/10th) SQ = 30 subjects.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
88

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Frederick, Maryland, United States, 21702
        • United States Army Medical Research Institute of Infectious Diseases

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Males and Females 18 to 50 years of age.
  2. In good health, as determined by pertinent medical history, physical examination, vital signs, and clinical safety laboratory evaluations.
  3. Female of child bearing potential: Has a negative pregnancy test and is willing to use a reliable form of contraception for the duration of the study after vaccination.
  4. Negative human immunodeficiency virus (HIV) antibody screen, seronegative for hepatitis B surface antigen (HBsAg) and hepatitis C antibody (following HIV and hepatitis testing, subjects will be provided with counseling and referral for health care if any test is positive).
  5. Ability to comprehend and a willingness to sign an informed consent, which includes the Health Insurance Portability and Accountability Act (HIPAA) Authorization, and a separate consent form for HIV testing.
  6. Be willing to comply with all follow-up visits, testing, adverse event (AE) reporting, and completion of diary card.

Exclusion Criteria:

  1. Receipt of any other investigational vaccine or investigational drug within 28 days prior to or after vaccination with YF-VAX® vaccine.
  2. Have had any known flavivirus disease or receipt of any flavivirus vaccine, licensed or investigational at any time; in addition to any yellow fever vaccine, these include; Japanese Encephalitis (JE), St. Louis Encephalitis, Tick Borne Encephalitis (TBE), West Nile, Dengue, Zika virus
  3. Anticipates receipt of any other vaccine within 28 days of YF-VAX®. Influenza vaccination will be permitted but not within 14 days of YF-VAX®.
  4. Acute or chronic medical conditions, or medications that, in the Principal Investigator's (PI) opinion, would impair the subject's ability to respond to vaccination.
  5. Hypersensitivity to any vaccine, eggs or egg products, or allergy to any component of the YF-VAX® (sorbitol, gelatin) or latex.
  6. Corticosteroids ≥20 mg/day of prednisone for ≥ 2 weeks suppresses the immune system. Low-dose corticosteroid topical products and nasal sprays used sporadically (i.e. prn--according to circumstances) are permissible.
  7. History of immunosuppression, by any cause--primary or acquired immunodeficiencies, transplantation, malignant neoplasm, lymphoma, leukemia, thymoma, myasthenia gravis, radiation, immunosuppressive drugs, including antimetabolites, tumor necrosis factor (TNF)-alpha inhibitors (etanercept), interleukin-1 (IL-1) blocking agents and other monoclonal antibodies targeting immune cells (e.g., rituximab, alemtuzumab, etc), etc.
  8. Receipt of or anticipates receipt of/or donation of blood or blood products for 2 months after receipt of YF-VAX®. (Note: Blood banks require a minimum 2 week interval between the receipt of this FDA licensed vaccine and blood donations; however because of the blood collections in this study, an interval of 2 months is requested).
  9. Female: Pregnant (or planning to become pregnant) or breastfeeding for the duration of the study after receipt of YF-VAX®.
  10. Clinically significant abnormal laboratory tests (generally 2 times the upper limit of normal or as determined by the PI).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Standard Dose (Group 1)
Yellow Fever vaccine standard dose, 0.5mL.
Biological: Yellow Fever Vaccine
Administered subcutaneously once.
Other Names:
  • YF-VAX
Experimental: Fractional dose (Group 2)
Yellow Fever vaccine 1/5th standard dose, 0.1mL.
Biological: Yellow Fever Vaccine
Administered subcutaneously once.
Other Names:
  • YF-VAX
Experimental: Fractional dose (Group 3)
Yellow Fever vaccine 1/10th standard dose, 0.05mL.
Biological: Yellow Fever Vaccine
Administered subcutaneously once.
Other Names:
  • YF-VAX

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: Up to 28 days post vaccination
Rate of Adverse Events of fractional doses vs standard dose of YF-VAX.
Up to 28 days post vaccination
Neutralizing Antibody Response
Time Frame: The primary data point is day 28 post-vaccination.
For each group determine the PRNT50 neutralizing antibody response rate at the primary data point at post-vaccination day 28.
The primary data point is day 28 post-vaccination.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Viremia
Time Frame: First 14 days following vaccination.
Compare the rate of viremia by Reverse Transcription Polymerase Chain Reaction (RT-PCR) [copies/mL] of fractional doses vs standard dose.
First 14 days following vaccination.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
US Army Medical Research Institute of Infectious Diseases

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Phillip R Pittman, M.D., M.P.H., US Army Medical Research Institute of Infectious Diseases

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 7, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 2, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 2, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 28, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 9, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 16, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 7, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 20, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • FY19-26

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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