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The Effect of Inflammation and Damage to Lymph Node Structures on Durable Protective Immunity Following Yellow Fever Vaccination

Primary Purpose

Yellow Fever

Status

Active

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Yellow Fever Vaccine

About this trial

This is an interventional basic science trial for Yellow Fever

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

No contraindication to Yellow Fever vaccine (immunosuppressed for any reason or on an immunosuppressive drug where a live virus vaccine is contraindicated).
If female of childbearing age must agree to contraception for one month following administration of the vaccination.

Exclusion Criteria:

History of yellow fever or previous vaccination for yellow fever
Known bleeding disorder
Prior surgery complicated by clotting abnormality
Psychiatric or behavioral disorder that, in the opinion of the investigator, will make it difficult for the participant to complete the study
History of acute hypersensitivity reaction to any component of the vaccine (including gelatin, eggs, egg products, or chicken protein).
Thymus disorder associated with abnormal immune function
Immunosuppression from any of the following: HIV infection or AIDS, malignant neoplasms, primary immunodeficiencies, transplantation, transplantation, immunosuppressive or immunomodulatory therapy (corticosteroids, alkylating agents, antimetabolites, TNF inhibitors, IL-1 blocking agents, monoclonal antibodies targeting immune cells), previous radiation therapy.
Pregnant or breastfeeding at the time of vaccination.
Planning to conceive within 28 days of enrollment and vaccination with the yellow fever vaccine.

Sites / Locations

University of Minnesota
Joint Clinical Research Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

All Participants

Arm Description

In this single-arm study, all participants will receive the intervention

Outcomes

Primary Outcome Measures

Peak Neutralizing Antibody Titer

Peak titer of neutralizing antibody to yellow fever vaccination. Outcome reported as Log YF Antibody titer.

Secondary Outcome Measures

Full Information

NCT ID

NCT04269265

First Posted

February 11, 2020

Last Updated

August 21, 2023

Sponsor

University of Minnesota

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

1. Study Identification

Unique Protocol Identification Number

NCT04269265

Brief Title

The Effect of Inflammation and Damage to Lymph Node Structures on Durable Protective Immunity Following Yellow Fever Vaccination

Official Title

The Effect of Inflammation and Damage to Lymph Node Structures on Durable Protective Immunity Following Yellow Fever Vaccination

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

July 1, 2020 (Actual)

Primary Completion Date

June 30, 2025 (Anticipated)

Study Completion Date

June 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Minnesota

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Hypothesis: Infections other than HIV can cause LN inflammation and collagen damage to the fibroblastic reticular cell network (FRCn), which will lead to CD4 T cell depletion and impaired vaccine responses. This protocol will study yellow fever vaccine (YFV) in two cohorts of people, one from Uganda and the other from Minnesota where we collect lymphoid tissues (LT) and peripheral blood monocytes (PBMCs) before and after vaccination using a new technique to catalog infectious burden of the individual, determine the relationship between IA, Infections, and immune response.

Detailed Description

The primary aim of this study is to determine the difference between antibody titers in the two study groups and study the relationship between endemic infections, IA, the FRCn, and CD4 and CD8 T cell subsets and the magnitude and durability of neutralizing antibody response to YFV in a cohort shown to have elevated IA, a damaged FRCn, and pan T cell depletion and a cohort that does not. This is a single arm, open-label, two cohort study of healthy adults in Kampala, Uganda and in Minnesota, USA. The cohort in Uganda will be 30 adults (15 men and 15 women) and the cohort in Minnesota will be 16 adults (8 men and 8 women). Everyone will be screened to ensure there are no contraindications to receiving YFV (e.g., immunosuppression) or the planned procedures. The inclusion and exclusion criteria are discussed in detail in the protocol that is included in the appendix. Participants will have an inguinal lymph node and adjacent adipose tissue biopsy and leukapheresis prior to YFV and again 3 weeks after the vaccine administration. The vaccine will be given in the contralateral thigh from the first LN biopsy so that the second biopsy will be from a draining LN. PBMC and plasma as well as urine and stool will be collected at regular intervals over the 18-month follow-up period and leukapheresis will be done again at the month 18 visit.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Yellow Fever

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

43 (Actual)

8. Arms, Groups, and Interventions

Arm Title

All Participants

Arm Type

Experimental

Arm Description

In this single-arm study, all participants will receive the intervention

Intervention Type

Biological

Intervention Name(s)

Yellow Fever Vaccine

Other Intervention Name(s)

YF-VAX

Intervention Description

YF-VAX®, Yellow Fever Vaccine, for subcutaneous use

Primary Outcome Measure Information:

Title

Peak Neutralizing Antibody Titer

Description

Peak titer of neutralizing antibody to yellow fever vaccination. Outcome reported as Log YF Antibody titer.

Time Frame

18 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: No contraindication to Yellow Fever vaccine (immunosuppressed for any reason or on an immunosuppressive drug where a live virus vaccine is contraindicated). If female of childbearing age must agree to contraception for one month following administration of the vaccination. Exclusion Criteria: History of yellow fever or previous vaccination for yellow fever Known bleeding disorder Prior surgery complicated by clotting abnormality Psychiatric or behavioral disorder that, in the opinion of the investigator, will make it difficult for the participant to complete the study History of acute hypersensitivity reaction to any component of the vaccine (including gelatin, eggs, egg products, or chicken protein). Thymus disorder associated with abnormal immune function Immunosuppression from any of the following: HIV infection or AIDS, malignant neoplasms, primary immunodeficiencies, transplantation, transplantation, immunosuppressive or immunomodulatory therapy (corticosteroids, alkylating agents, antimetabolites, TNF inhibitors, IL-1 blocking agents, monoclonal antibodies targeting immune cells), previous radiation therapy. Pregnant or breastfeeding at the time of vaccination. Planning to conceive within 28 days of enrollment and vaccination with the yellow fever vaccine.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Timothy Schacker, MD

Organizational Affiliation

University of Minnesota

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Minnesota

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55455

Country

United States

Facility Name

Joint Clinical Research Centre

City

Kampala

ZIP/Postal Code

10005

Country

Uganda

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

The Effect of Inflammation and Damage to Lymph Node Structures on Durable Protective Immunity Following Yellow Fever Vaccination

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