Human Immune Responses to Yellow Fever Vaccination

The goal of this study is to use the live attenuated yellow fever vaccine, YFV-17D (YF-VAX®, Sanofi-Pasteur) as a safe and effective model for viral infection to understand human immune response to viral antigens. Study participants will receive the yellow fever vaccine and participation in the study may be as short as one month or as long as one year, depending on immune responses.

Yellow fever is a viral disease that is transmitted to humans through the bite of an infected mosquito. Yellow fever is a life-threatening infection that can result in hepatitis, renal failure and coagulation abnormalities, and in severe cases, death. Yellow fever was a major public health threat in the colonial United States in the 18th and 19th centuries. Yellow fever is endemic in over 40 countries, and approximately 125 countries require proof of vaccination for entry by travelers at risk. An estimated 200,000 cases of yellow fever occur annually in South America and Africa, making it an important vaccine-preventable disease among travelers to endemic areas. Yellow fever can be prevented by vaccination with the yellow fever vaccine (YFV-17D). Currently, the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) recommend yellow fever vaccination for persons ≥ 9 months of age who are traveling to or living in a yellow fever endemic area. The YFV-17D vaccine is considered to be one of the safest and most effective viral vaccines ever developed. YFV-17D vaccine is known to stimulate broad-spectrum immune responses, including cytotoxic T cells, and Th1 and Th2 responses, as well as neutralizing antibody titers that can persist for up to 30 years, after a single vaccination. Despite the great success of this empiric vaccine, there has been relatively little understanding of the mechanisms by which YFV-17D induces such robust protective immune responses. The researchers hope to apply the best contemporary methods in immunology, genomics, and proteomics to characterize in detail a successful immune response to YFV-17D vaccination. This characterization should identify new immunologic predictors that could serve as surrogates for future vaccine efficacy studies. In addition, these findings could guide development of a safer yellow fever vaccine (or the derivation of safer alternative vaccination regimens using the currently available vaccine). This study plans to recruit both travelers to yellow fever endemic areas as well as non-travelers for participation. Participants will be followed for up to 360 days post-vaccination.

Participants will receive the FDA-approved YFV-17D vaccine, at the FDA approved dose and route of administration.

The characterization of yellow fever vaccine (YFV-17D) specific adaptive immune response will be examined as the magnitude of YFV-specific T cell responses. The schedule of follow up visits depends on if participants test positive for human leukocyte antigen (HLA) A202 and the different immune system responses that the study team is examining at the time when each participant enrolls.

The characterization of yellow fever vaccine (YFV-17D) specific adaptive immune response will be examined as the quality of YFV-specific T cell responses. The schedule of follow up visits depends on if participants test positive for HLA-A202 and the different immune system responses that the study team is examining at the time when each participant enrolls.

The characterization of yellow fever vaccine (YFV-17D) specific adaptive immune response will be examined as the magnitude of YFV-specific antibody secreting cells. The schedule of follow up visits depends on if participants test positive for HLA-A202 and the different immune system responses that the study team is examining at the time when each participant enrolls.

The characterization of yellow fever vaccine (YFV-17D) specific adaptive immune response will be examined as the quality of YFV-specific antibody secreting cells. The schedule of follow up visits depends on if participants test positive for HLA-A202 and the different immune system responses that the study team is examining at the time when each participant enrolls.

The characterization of yellow fever vaccine (YFV-17D) specific adaptive immune response will be examined as the magnitude of YFV-specific memory B cells. The schedule of follow up visits depends on if participants test positive for HLA-A202 and the different immune system responses that the study team is examining at the time when each participant enrolls.

The characterization of yellow fever vaccine (YFV-17D) specific adaptive immune response will be examined as the quantity of YFV-specific memory B cells. The schedule of follow up visits depends on if participants test positive for HLA-A202 and the different immune system responses that the study team is examining at the time when each participant enrolls.

To determine the signatures of innate immune responses, cytokines on peripheral blood mononuclear cells (PBMCs) will be examined. The schedule of follow up visits depends on if participants test positive for HLA-A202 and the different immune system responses that the study team is examining at the time when each participant enrolls.

To determine the signatures of innate immune responses, chemokines on PBMCs will be examined. The schedule of follow up visits depends on if participants test positive for HLA-A202 and the different immune system responses that the study team is examining at the time when each participant enrolls.

To determine the signatures of innate immune responses, dendritic cells on PBMCs will be examined. The schedule of follow up visits depends on if participants test positive for HLA-A202 and the different immune system responses that the study team is examining at the time when each participant enrolls.

To determine the signatures of innate immune responses, microarray analyses for gene expression on PBMCs will be performed. The schedule of follow up visits depends on if participants test positive for HLA-A202 and the different immune system responses that the study team is examining at the time when each participant enrolls.

Characterization of EBV cluster of differentiation 8 (CD8) T cells will be performed. The schedule of follow up visits depends on if participants test positive for HLA-A202 and the different immune system responses that the study team is examining at the time when each participant enrolls.

Phenotypic analysis of EBV CD8 T cells will be performed. The schedule of follow up visits depends on if participants test positive for HLA-A202 and the different immune system responses that the study team is examining at the time when each participant enrolls.

Characterization of CMV CD8 T cells will be performed. The schedule of follow up visits depends on if participants test positive for HLA-A202 and the different immune system responses that the study team is examining at the time when each participant enrolls.

Phenotypic analysis of CMV CD8 T cells will be performed. The schedule of follow up visits depends on if participants test positive for HLA-A202 and the different immune system responses that the study team is examining at the time when each participant enrolls.

Characterization of YFV CD8 T cells will be performed. The schedule of follow up visits depends on if participants test positive for HLA-A202 and the different immune system responses that the study team is examining at the time when each participant enrolls.

Phenotypic analysis of YFV CD8 T cells will be performed. The schedule of follow up visits depends on if participants test positive for HLA-A202 and the different immune system responses that the study team is examining at the time when each participant enrolls.

Inclusion Criteria: Able to understand and give informed consent Age 18-45 years If possible, participants agree not to take any vaccines within 30 days before or 30 days after yellow fever vaccination Women of child bearing potential must agree to use effective birth control throughout the duration of the study. A negative urine pregnancy test must be documented prior to vaccination. Exclusion Criteria: Lived in a country/area which is endemic for yellow fever History of previous yellow fever, West Nile, Dengue, St. Louis encephalitis, Japanese encephalitis vaccination or infection Any history of allergy to eggs, chicken or gelatin or to any previous vaccine A history of a medical condition resulting in impaired immunity (such as HIV infection, cancer, particularly leukemia, lymphoma, use of immunosuppressive or antineoplastic drugs or X-ray treatment). Persons with previous skin cancers or cured non-lymphatic tumors are not excluded from the study. History of HIV infection, Hepatitis B or Hepatitis C infection History of any chronic medical conditions that are considered progressive (ex, diabetes, heart disease, lung disease, liver disease, kidney disease, gastrointestinal diseases and uncontrolled hypertension). Use of systemic immunosuppressive medications (ex, prednisone) for 2 weeks or more in the past 3 months History of excessive alcohol consumption, drug abuse, psychiatric conditions, social conditions or occupational conditions that in the opinion of the investigator would preclude compliance with the trial Thymus gland problems (such as myasthenia gravis, DiGeorge syndrome, thymoma) or removal of thymus gland or history of autoimmune disorder Recipient of a blood products or immune globulin product within 42 days of the vaccination visit Pregnant women and nursing mothers or women who are planning to become pregnant for the study duration Any condition in the opinion of the investigator that would interfere with the proper conduct of the trial Received the second coronavirus disease 2019 (COVID-19) vaccine less than 21 days before receiving the Yellow Fever Vaccine. COVID-19 infection in the last 60 days. Symptoms of COVID-19 symptoms must be completely resolved before yellow fever vaccine receipt.