Serum Hemagglutination Inhibition Assay as a Method for Studying the Dynamics of Immune Response to Norovirus Infection Open Access

Park, Kyung (2014)

Permanent URL: https://etd.library.emory.edu/concern/etds/05741s31j?locale=en
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Abstract

Norovirus infections are a common cause of epidemic gastroenteritis. It is estimated that over 50% of all gastroenteritis outbreaks worldwide are attributable to norovirus. Norovirus infection is typically acute, mild, and of short duration. However, the disease can present much more severely with longer duration in infants, the elderly, and immune-compromised individuals. Despite norovirus being recognized as a leading cause of major global epidemics, immune response to infection remains poorly understood. In this study, serum hemagglutination inhibition (HAI) assay was used to measure the immune response of 43 volunteers challenged with Norwalk virus (GI.1) and 15 volunteers challenged with Snow Mountain virus (GII.2). Hemagglutination inhibition activity was observed from all 13 of the infected volunteers of the 43 challenged with GI.1, and all 9 of the infected volunteers of the 15 challenged with GII.2. HAI titers increased significantly for individuals infected with either virus. The magnitude of increase was correlated with the magnitude of increase in α-norovirus serum IgG concentration, infection status and presentation of symptoms. Baseline titers were not associated with protection from infection or presentation of symptoms. Although the amount of viral shedding among infected volunteers was found to be associated with HAI titer in the Snow Mountain virus challenge group, there was no significant association found between the amount of viral shedding and HAI titer for the Norwalk virus challenge group. There was no evidence of correlation between duration of viral shedding and HAI titer in either challenge study groups.

Table of Contents

LITERATURE REVIEW... 1 NOROVIRUS BACKGROUND AND HISTORY...1 VIRUS CLASSIFICATION...2 Structural Characteristics... 2 Genetic Diversity and Classification... 2 GLOBAL IMPACT OF NOROVIRUS...3 The Burden of Norovirus in Developing Nations ...3 The Burden of Norovirus in Developed Nations...6 EPIDEMIOLOGY OF NOROVIRUS...8 Epidemiology... 8 Transmission... 9 Clinical Presentation of Infection... 11 NOROVIRUS IMMUNITY AND SUSCEPTIBILITY...12 Susceptibility to Norwalk Virus (GI.1 )... 12 Susceptibility to Snow Mountain virus (GII.2) and other noroviruses... 14 Immunity... 15 HEMAGGLUTINATION INHIBITION AS A METHOD FOR STUDYING IMMUNE RESPONSE TO NOROVIRUSINFECTION...17 FUTURE OF NOROVIRUS RESEARCH AND SIGNIFICANCE OF STUDY...18 MANUSCRIPT... 27 ABSTRACT...28 INTRODUCTION... 29 MATERIALS AND METHODS... 31 NORWALK VIRUS HUMAN CHALLENGE STUDY ...31 SNOW MOUNTAIN VIRUS HUMAN CHALLENGE STUDY... 31 MEASUREMENT OF α-NOROVIRUS SERUM IgG LEVELS...32 ASSESSMENT OF SECRETOR STATUS USING ELISA ...32 HEMAGGLUTINATION INHIBITION ASSAY ...33 STATISTICAL METHODS ...36 RESULTS ...37 VOLUNTEER CHARACTERISTICS ...37 CHARACTERISTICS OF CLINICAL ILLNESS ...37 CORRELATES OF INFECTION ...39 CORRELATES OF VIRAL SHEDDING ...39 CORRELATES OF α-NOROVIRUS SERUM IgG RESPONSE...40
DISCUSSION...42 SERUM HEMAGGLUTINATION ACTIVITY ...42 LIMITATIONS...45 CONCLUSIONS AND PUBLIC HEALTH IMPLICATIONS... 67


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