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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04269265
Recruitment Status : Recruiting
First Posted : February 13, 2020
Last Update Posted : October 21, 2022
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
University of Minnesota

Study Description
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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.

Condition or disease Intervention/treatment Phase
Yellow Fever Biological: Yellow Fever Vaccine Phase 1 Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 46 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: The Effect of Inflammation and Damage to Lymph Node Structures on Durable Protective Immunity Following Yellow Fever Vaccination
Actual Study Start Date : July 1, 2020
Estimated Primary Completion Date : June 30, 2025
Estimated Study Completion Date : June 30, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Fever Vaccines

Arms and Interventions
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Arm Intervention/treatment
Experimental: All Participants
In this single-arm study, all participants will receive the intervention
 Biological: Yellow Fever Vaccine
YF-VAX®, Yellow Fever Vaccine, for subcutaneous use
Other Name: YF-VAX


Outcome Measures
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Primary Outcome Measures :
  1. Peak Neutralizing Antibody Titer [ Time Frame: 18 months ]
    Peak titer of neutralizing antibody to yellow fever vaccination. Outcome reported as Log YF Antibody titer.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04269265


Contacts
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Contact: Kevin Escandon, MD, MSc 612-626-9344 escan012@umn.edu

Locations
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United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Timothy Schacker, MD    612-626-6577    olso7966@umn.edu   
Uganda
Joint Clinical Research Centre Not yet recruiting
Kampala, Uganda, 10005
Contact    +256-752769168      
Sponsors and Collaborators
University of Minnesota
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Timothy Schacker, MD University of Minnesota
More Information
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Responsible Party: University of Minnesota
ClinicalTrials.gov Identifier: NCT04269265    
Other Study ID Numbers: IDIM-2018-27222
U01AI141981 ( U.S. NIH Grant/Contract )
First Posted: February 13, 2020    Key Record Dates
Last Update Posted: October 21, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Yellow Fever
Inflammation
Fever
Pathologic Processes
Body Temperature Changes
Arbovirus Infections
Vector Borne Diseases
 Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral