Ignite Creation Date:
2024-05-05 @ 11:17 PM
Last Modification Date:
2024-10-26 @ 10:31 AM
Study NCT ID:
NCT01290055
Status:
COMPLETED
Last Update Posted:
2023-12-28
First Post:
2011-02-03
Brief Title:
Turnover of Antigen Specific Lymphocytes and Monocytes After Immunization With the 17D Yellow Fever Vaccine
Sponsor:
Sri Edupuganti
Organization:
Emory University
Study Overview
Official Title:
Yellow Fever Heavy Water Turnover of Antigen Specific Lymphocytes and Monocytes After Immunization With the 17D Yellow Fever Vaccine
Status:
COMPLETED
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The yellow fever vaccine is a live attenuated virus that results in a robust immune response especially in the T cell compartment The researchers have been studying immune responses to live viral infections using the yellow fever vaccine as a model for a live viral infection In this study the researchers are interested in looking at the processing and lifespan of yellow fever specific CD8 T cell by measuring DNA replication and cell proliferation in humans using a naturally occurring stable isotope called deuterium
Detailed Description:
Yellow fever is a viral disease caused by the yellow fever virus YFV It is transmitted to humans through the bite of an infected mosquito and can result in a life-threatening infection with hepatitis renal failure and coagulation abnormalities and in severe cases death 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 vaccination for persons 9 months of age who are traveling to or living in a yellow fever endemic area
A very interesting but unexplained aspect of flavivirus biology is how infection with different members of the same virus family can lead to such diverse types of host-virus interactions and variable disease outcomes For example YFV infection can be fatal but if the infected host survives long-term protective immunity is seen Alternatively dengue virus causes an acute infection with associated acute disease manifestations however even more severe disease outcomes are observed following secondary infection with a distinct serologic type of dengue virus Understanding why the human immune system can successfully contain one flavivirus infection but not another is both a fascinating scientific enigma in human immunology and a topic with substantial practical importance to public health Given the great global public health threats posed by epidemic and emerging flavivirus infections and the need to define the biological basis of successful induction and maintenance of protective immunity by vaccination elucidation of the immunologic mechanisms underlying the generation and maintenance of protective immunity to YFV vaccine should be extremely useful Furthermore definition of the attributes of such a highly effective vaccine should help expedite the development and evaluation of new andor improved vaccines to prevent important prevalent and emerging infectious diseases
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 to study a primary acute viral infection in humans Yellow fever virus vaccine is the viral infection model that the researchers have chosen for the following reasons
The 17D attenuated yellow fever vaccine strain is one of the most efficacious vaccines available and has been in use since the 1930s
YFV vaccination leads to limited infection without causing the disease
Since most of the US population is not exposed to yellow fever virus immunization of adult participants with the 17D vaccine strain allows for examination of the innate immunity and the naïve T and B cell response in humans during primary infection and the subsequent development of memory T cells after resolution of the primary infection
The YFV-17D vaccine induces long-term immunity that lasts for decades By studying how the human immune system responds to an effective vaccine such as the YFV-17D vaccine the researchers hope to learn more about the normal functioning of the immune system so that it might be possible to design new more effective vaccines to prevent important infectious diseases Therefore this vaccine can serve as an ideal model to help decipher the properties that make a vaccine effective
YFV-17D 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
This study seeks to understand the lifespan and decay curve of effector CD8 T cells and the rate of homeostatic turnover of memory CD8 T cells after YFV-17D immunization using an innovative method developed by Dr Marc Hellersteins group at the University of California Berkeley for measuring DNA replication and cell proliferation in humans using a naturally occurring stable isotope called deuterium 2H This technique has been used to track the turnover of a number of human cell types in vivo The researchers plan to use 2H labeling to track YFV specific CD8 T cells in human vaccinees HLA-A2 positive participants only The availability of a T cell epitope A2-NS4B214 a major component of the human YFV specific CD8 T cell response allows for the longitudinal analysis of virus specific CD8 T cells The unique feature of this study is that it allows for tracking of differentiation of YFV specific CD8 T cells in humans Thus the researchers can overcome the inherent limitations due to heterogeneity in cross sectional studies that involve bulk CD8 T cells
In addition the researchers are proposing to study the life span and decay curve of monocytes after YFV vaccination The mononuclear phagocytes comprise three types of cells monocytes macrophages and dendritic cells DCs Mononuclear phagocytes play key functions in maintaining tissue homeostasis during steady state as well as orchestrating the genesis and resolution of the immune response The kinetics underlying their generation differentiation and disappearance are critical to understanding both steady-state homeostasis and inflammatory responses Using human in vivo deuterium labeling it has been shown that classical monocytes emerge first from marrow after a postmitotic interval of 16 days and circulate for a day Subsequent labeling of intermediate and nonclassical monocytes is consistent with a model of sequential transition Intermediate and nonclassical monocytes have longer circulating lifespans 4 and 7 days respectively It is of great interest to determine the lifespan and decay of monocytes post-viral infection as modeled by administration of a live attenuated yellow fever vaccination
Deuterium labeled water 2H2O or heavy water is chemically nearly the same as normal water but the hydrogen atoms are of the heavy isotope deuterium in which the nucleus of the hydrogen atom contains a neutron in addition to the proton When a person drinks 2H2O it mixes with the body water Proteins DNA RNA lipids and other biomolecules become labeled the faster the biomolecules are being synthesized the more they become labeled with deuterium The deuterium labeled molecules can be measured by sampling blood and body fluids such as plasma cerebrospinal fluid sputum urine etc
Participants will enroll into one of 8 study arms and will be given repeated small doses of 2H2O to drink and may receive the yellow fever vaccine depending on the study arm they are in
A very interesting but unexplained aspect of flavivirus biology is how infection with different members of the same virus family can lead to such diverse types of host-virus interactions and variable disease outcomes For example YFV infection can be fatal but if the infected host survives long-term protective immunity is seen Alternatively dengue virus causes an acute infection with associated acute disease manifestations however even more severe disease outcomes are observed following secondary infection with a distinct serologic type of dengue virus Understanding why the human immune system can successfully contain one flavivirus infection but not another is both a fascinating scientific enigma in human immunology and a topic with substantial practical importance to public health Given the great global public health threats posed by epidemic and emerging flavivirus infections and the need to define the biological basis of successful induction and maintenance of protective immunity by vaccination elucidation of the immunologic mechanisms underlying the generation and maintenance of protective immunity to YFV vaccine should be extremely useful Furthermore definition of the attributes of such a highly effective vaccine should help expedite the development and evaluation of new andor improved vaccines to prevent important prevalent and emerging infectious diseases
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 to study a primary acute viral infection in humans Yellow fever virus vaccine is the viral infection model that the researchers have chosen for the following reasons
The 17D attenuated yellow fever vaccine strain is one of the most efficacious vaccines available and has been in use since the 1930s
YFV vaccination leads to limited infection without causing the disease
Since most of the US population is not exposed to yellow fever virus immunization of adult participants with the 17D vaccine strain allows for examination of the innate immunity and the naïve T and B cell response in humans during primary infection and the subsequent development of memory T cells after resolution of the primary infection
The YFV-17D vaccine induces long-term immunity that lasts for decades By studying how the human immune system responds to an effective vaccine such as the YFV-17D vaccine the researchers hope to learn more about the normal functioning of the immune system so that it might be possible to design new more effective vaccines to prevent important infectious diseases Therefore this vaccine can serve as an ideal model to help decipher the properties that make a vaccine effective
YFV-17D 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
This study seeks to understand the lifespan and decay curve of effector CD8 T cells and the rate of homeostatic turnover of memory CD8 T cells after YFV-17D immunization using an innovative method developed by Dr Marc Hellersteins group at the University of California Berkeley for measuring DNA replication and cell proliferation in humans using a naturally occurring stable isotope called deuterium 2H This technique has been used to track the turnover of a number of human cell types in vivo The researchers plan to use 2H labeling to track YFV specific CD8 T cells in human vaccinees HLA-A2 positive participants only The availability of a T cell epitope A2-NS4B214 a major component of the human YFV specific CD8 T cell response allows for the longitudinal analysis of virus specific CD8 T cells The unique feature of this study is that it allows for tracking of differentiation of YFV specific CD8 T cells in humans Thus the researchers can overcome the inherent limitations due to heterogeneity in cross sectional studies that involve bulk CD8 T cells
In addition the researchers are proposing to study the life span and decay curve of monocytes after YFV vaccination The mononuclear phagocytes comprise three types of cells monocytes macrophages and dendritic cells DCs Mononuclear phagocytes play key functions in maintaining tissue homeostasis during steady state as well as orchestrating the genesis and resolution of the immune response The kinetics underlying their generation differentiation and disappearance are critical to understanding both steady-state homeostasis and inflammatory responses Using human in vivo deuterium labeling it has been shown that classical monocytes emerge first from marrow after a postmitotic interval of 16 days and circulate for a day Subsequent labeling of intermediate and nonclassical monocytes is consistent with a model of sequential transition Intermediate and nonclassical monocytes have longer circulating lifespans 4 and 7 days respectively It is of great interest to determine the lifespan and decay of monocytes post-viral infection as modeled by administration of a live attenuated yellow fever vaccination
Deuterium labeled water 2H2O or heavy water is chemically nearly the same as normal water but the hydrogen atoms are of the heavy isotope deuterium in which the nucleus of the hydrogen atom contains a neutron in addition to the proton When a person drinks 2H2O it mixes with the body water Proteins DNA RNA lipids and other biomolecules become labeled the faster the biomolecules are being synthesized the more they become labeled with deuterium The deuterium labeled molecules can be measured by sampling blood and body fluids such as plasma cerebrospinal fluid sputum urine etc
Participants will enroll into one of 8 study arms and will be given repeated small doses of 2H2O to drink and may receive the yellow fever vaccine depending on the study arm they are in
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U19AI057266 | NIH | None | httpsreporternihgovquickSearchU19AI057266 |