Yellow Fever Immune Response at Single Cell Resolution
Yellow Fever Immune Response at Single Cell Resolution
The immune system is composed of diverse cell types with different functions that act
 together in order to defend against infection. This pilot study will test a new technology
 for studying these many different cell types at very large numbers at the level of individual
 cells. This method will then be used to identify the cell types and functions important for
 the immune response to the highly protective yellow fever vaccine, which will improve our
 understanding of effective vaccine features.
Vaccines have had monumental impact in reducing the mortality and morbidity of infectious
 disease. However, the underlying immune mechanisms that contribute to their effectiveness are
 incompletely understood. Transcriptomics (methods that measure the activity of thousands of
 genes) studies have identified key features of responses to vaccination(see references) and
 infection(see references). However, these experiments are typically performed on
 heterogeneous cell mixtures such as peripheral blood mononuclear cells (PBMC which include
 certain types of white blood cells) and therefore provide an aggregate measure of gene
 expression from the many different immune cells and their respective activities in the
 mixture. Such results can obscure important biological information, particularly in minor
 subsets of active cells. Establishing a method for immune transcriptomics at single cell
 resolution would be a highly significant advance and enable more informative and functionally
 relevant systems immunology studies with commonly used sample types (i.e. PBMC). Applying
 this high-resolution approach to Yellow Fever Vaccine (YFV), an exceptionally effective
 vaccine, is likely to identify unappreciated mechanisms that contribute to protective
 immunity.
Inclusion Criteria:

 -  Male or female between the ages of 18 and 59 years old

 -  Volunteers who have not received a vaccination within 30 days of the YFV and do not
 anticipate to receive a vaccination within 30 days

 -  Volunteers who are seeking the YFV for either travel reasons or occupational risk

 -  Volunteers willing to undergo one screening visit, one visit to receive the YFV, and
 four post-vaccination visits

 -  Volunteers without medical conditions who are willing to give blood once for the
 development of the inDrop technique

 Exclusion Criteria:

 -  Male or females under 18 or over 59 years of age

 -  Volunteers who received other vaccination less than 30 days prior to receiving the YFV

 -  Volunteers with acute or febrile disease

 -  Volunteers unable to return for the post vaccination follow-up visits

 -  Volunteers with an allergy to eggs, chicken proteins, gelatin, or other components of
 the Yellow Fever vaccine

 -  Participation in another clinical study of an investigational product currently or
 within the past 90 days, or expected participation during this study

 -  Is pregnant or lactating

 -  Volunteers with a history of yellow fever vaccination and/or infection

 -  Volunteers with a history of viral hepatitis and/or non-viral liver disease

 -  In the opinion of the investigators, the volunteer is unlikely to comply with the
 study protocol

 -  Immunosuppressed individuals as a result of cancer, transplantation, and or primary
 immunodeficiency

 -  Immunosuppressed individuals as a result of medications (such as high-dose systemic
 corticosteroids, alkylating drugs, antimetabolites, TNF-α inhibitors (e.g.,
 etanercept), IL-1 blocking agents (e.g., anakinra), and other monoclonal antibodies
 targeting immune cells (e.g.,rituximab, alemtuzumab) and/or radiation

 -  Volunteers with thymus disorders (including myasthenia gravis, Di George syndrome, or
 thymoma) and/or history of thymectomy

 -  Individuals infected with HIV