Immune Response to Experimental Norwalk Virus Infection Open Access

Kirby, Amy (2012)

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An abstract of
A thesis submitted to the Faculty of the
Rollins School of Public Health of Emory University
in partial fulfillment of the requirements for the degree of
Master of Public Health
in Epidemiology

In the US, it is estimated that 21 million people are infected with norovirus every year. For the vast majority of these individuals, the infection will cause a mild gastroenteritis lasting 1-2 days. However, more severe outcomes are possible. Despite this very high incidence, the immunological response to norovirus infection, and, more importantly, the markers of a protective response, are poorly characterized. In this study, the immune response of 16 infected and 35 challenged-but-uninfected volunteers was monitored after an experimental challenge with Norwalk virus (GI.1). The dynamics of the humoral response were assessed by measuring the α-Norwalk serum IgG concentration. Similarly, α-Norwalk salivary IgA was used as an indicator of the mucosal response. The humoral, but not the mucosal, response was found to be highly predictive of infection status, with all but one infected volunteer seroconverting. Conversely, whether a given infection was symptomatic was correlated with the general, but not specific mucosal response; volunteers with illness had a higher final total salivary IgA titer than did those without symptoms. The presence of symptoms was not correlated with an α-Norwalk serum IgG response. Pre-existing antibodies, either serum IgG or salivary IgA, were not correlated with infection. Finally, longer periods of viral shedding were correlated with stronger mucosal responses, as measured by total salivary IgA.

Table of Contents

Table of Contents

Introduction to Norovirus...1

Norovirus Epidemiology...2
Viral Structure, Biology and Phylogeny...4
Norovirus Infection and Susceptibility...9
Norovirus Transmission and Environmental Stability...12
Immune Response to Norovirus...15
Potential Vaccines and Antivirals for Norovirus...18
Outstanding Research Questions...20

Assay Optimization...40

Serum IgG ELISA...41
Salivary IgA ELISA...43

Immune Response to Experimental Norwalk Virus Infection...49

Materials and Methods...52

Public Health Implications and Future Directions...74

Public Health Implications...75
Future Directions...77

List of Tables and Figures

Figure 1. Structure of Norovirus...5
Figure 2. Norovirus Classification Tree...8
Figure 3. Comparison of baculovirus- and VEE-produced Norwalk VLPs...45
Figure 4. Evaluation of BLOTTO and BSA as blocking agents and heat inactivation of serum...46
Figure 5. Comparison of different VLPs in the salivary IgA ELISA...47
Table 1. Characteristics of Volunteers by Infection Status...63
Table 2. Distribution of Antibody Concentrations by Infection Status...64
Table 3. Bivariate Analysis for Correlates of Infection...65
Table 4. Bivariate Analysis for Correlates of Symptomatic Infection...66
Table 5. Bivariate Analysis for Correlates of Duration of Viral Shedding...67
Figure 6. Temporal Dynamics of Serum IgG Response to Norwalk Virus Infection...68
Figure 7. Infection With Norwalk Virus Did Not Induce a Virus-specific Salivary IgA Response...69

About this Master's Thesis

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