Investigating heterogeneity in the dynamics of virus and immune response following a yellow fever vaccination Open Access

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

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

About this Honors Thesis

Rights statement

• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Emory College
Department	Biology
Degree	BS
Submission	Honors Thesis
Language	English
Research Field	Biology, Bioinformatics Biology, Ecology Biology, General
Keyword	heterogeneity within host dynamics of infection yellow fever vaccination
Committee Chair / Thesis Advisor	Antia, Rustom, Emory University
Committee Members	Waller, Lance, Emory University Eisen, Arri, Emory University De Roode, Jacobus, Emory University

Last modified

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 13:12:26 -0400	Press to Select an action Download

Supplemental Files

Thumbnail	Title	Date Uploaded	Actions