Investigating heterogeneity in the dynamics of virus and immune response following a yellow fever vaccination. 公开
Jia, Johnathan Dexuan (2015)
Published
Abstract
A key feature of the dynamics of infection in humans is
that different individuals form different responses to a given
pathogen. This has been demonstrated in recent studies conducted by
Akondy et al. (2015) following immunization of the yellow fever
vaccine. Their results show that there is a 104 fold
variation in the peak viral titer and 102 fold variation
in the peak immune cell density among human participants. We used
simple mathematical models of the within host dynamics of infection
to investigate what gives rise to variation between individuals in
the dynamics of infection and immunity. We found that changes in
most parameters over biologically reasonable ranges resulted in
greater changes in peak viral load compared to the peak immune cell
density. Only changes in the killing rate of adaptive immunity
resulted in similar changes in the peak viral load and peak immune
cell density. Our simple model does not recapitulate the yellow
fever vaccination data. This indicates that our model assumptions
are incorrect. Since our model is the simplest case, we must have
failed to consider an important process or factor that would be
necessary to recapitulate the observed variation in the yellow
fever vaccination data. However our model makes predictions which
can be experimentally tested, and in doing so it sets the stage for
a quantitative understanding of what gives rise to heterogeneity in
the responses of different individuals and infection.
Table of Contents
Table of Contents
Abstract pg. 1
Background pg. 2
The Question and the Problem pg. 2
Sources of Heterogeneity pg. 5
How do genetic factors impact the within-host dynamics of
infection? pg. 6
How do environmental factors impact the dynamics of infection
within a host? pg. 7
How does pathogen heterogeneity affect the immune response? pg.
8
How do other heterogeneous factors influence the dynamics of an
acute infection? pg. 9
Our Approach pg. 9
Model pg. 10
Model Schematic pg. 10
Assumptions pg. 11
Model Equations pg. 11
Parameterization pg. 12
Results
Variation in Viral Growth Rate: r pg. 16
Variation in Immune Growth Rate: s pg. 17
Variation in the Pathogen Density at which Immunity Responds:
φ pg. 18
Variation in the Rate of Killing of Pathogen by Adaptive Immunity:
k pg. 19
Variation in the Initial Viral Load: V(0) pg. 20
Variation in Initial Immunity: X(0) pg. 21
Summarization of the Results pg. 22
Discussion pg. 23
Viral Growth Rate pg. 23
Immune Growth Rate pg. 24
Pathogen Density at which Immunity Responds pg. 25
Killing Rate by Adaptive Immunity pg. 25
Initial Viral Inoculum pg. 26
Initial Immunity pg. 27
Summary: The Questions Revisited pg. 27
Limitations and Future Directions pg. 30
References pg. 31
Appendix pg. 34
Code pg. 34
Figures and Tables
Figures
Dynamics of the CD8 T-Cell Response in mice after infection by
Lymphocytic choriomeningitis pg. 4
Dynamics of Infection and Immunity in humans after yellow fever
vaccination pg. 5
Model Schematic pg. 10
Model simulation with parameters equal to the mean values pg.
14
Variation in Viral Growth Rate: r pg. 16
Variation in Immune Growth Rate: s pg. 17
Variation in the Pathogen Density at which Immunity Responds:
φ pg. 18
Variation in the Rate of Killing of Pathogen by Immunity: k pg.
19
Variation in the Initial Viral Load: V(0) pg. 20
Variation in Initial Immunity: X(0) pg. 21
Summarization of Results pg. 23
Tables
Model parameter units, definitions, mean values, and simulation
ranges pg. 12
Summarization of the results pg. 22
About this Honors Thesis
| School | |
|---|---|
| Department | |
| Degree | |
| Submission | |
| Language |
|
| Research field | |
| 关键词 | |
| Committee Chair / Thesis Advisor | |
| Committee Members |
Primary PDF
| Thumbnail | Title | Date Uploaded | Actions |
|---|---|---|---|
|
|
Investigating heterogeneity in the dynamics of virus and immune response following a yellow fever vaccination. () | 2018-08-28 |
|
Supplemental Files
| Thumbnail | Title | Date Uploaded | Actions |
|---|