Assessing the Histo-Blood Group Antigen Blocking Antibody Response against GII.2 Norovirus (Snow Mountain Virus) Öffentlichkeit
Ibaraki, Makoto (Spring 2021)
Published
Abstract
Noroviruses are one of the most common viral causes of acute gastroenteritis (AGE) globally, and each year, an estimated 684 million infections occur among both children and adults. Noroviruses can be classified into 48 genotypes and while the GII.4 has predominantly been the genotype associated with outbreaks worldwide, reports of outbreaks associated with the GII.2 genotype has recently been increasing. To determine the histo-blood group antigen (HBGA) blocking antibody response following GII.2 norovirus (Snow Mountain Virus, SMV) exposure, results from a recently conducted randomized, double blind, placebo-controlled SMV human challenge study were utilized. For the trial, SMV-specific serum immunoglobulin (Ig)A and IgG concentrations were measured through enzyme-linked immunosorbent assays (ELISA) while HBGA-blocking antibody titers were determined through a SMV-specific blockade assay. Serum antibody responses of SMV-specific IgA, IgG, and HBGA-blocking antibodies were all significantly different between SMV-infected and uninfected subjects following SMV challenge. Among the infected individuals, significant increases in HBGA-blocking antibodies were observed after receiving SMV, with the greatest increase observed on day 15 post-challenge when compared to the pre-challenge titer. The significant increases only observed among the infected subjects suggested that SMV exposure alone would not be enough to activate HBGA-blocking antibody response and that this HBGA-blocking antibody response is a reaction to SMV infection. While further research is needed in order to determine the other factors associated with SMV infection and illness, the results can be applied for the global population at risk. Findings from this study should be used to guide vaccine and screening tool development for SMV with the goal to reduce the infection and illness associated with SMV throughout the world.
Table of Contents
CHAPTER I: BACKGROUND 1
A. HISTORY OF SNOW MOUNTAIN VIRUS 1
B. STRUCTURE OF NOROVIRUSES AND CLASSIFICATION 3
C. CLINICAL FEATURES OF NOROVIRUS INFECTIONS 6
D. NOROVIRUS TRANSMISSION 8
E. NOROVIRUS EPIDEMIOLOGY 9
F. GLOBAL PREVALENCE AND BURDEN OF NOROVIRUS 11
G. MOLECULAR AND SEROLOGICAL DIAGNOSTIC METHODS 13
H. NOROVIRUS HUMAN CHALLENGE STUDIES 27
I. NOROVIRUS VACCINE STUDIES 30
CHAPTER II: MANUSCRIPT 33
A. TITLE, AUTHORS, ABSTRACT 33
B. INTRODUCTION 33
C. MATERIALS AND METHOD 37
i. CLINICAL STUDY DESIGN 37
ii. SEROLOGY 39
iii. STATISTICAL METHODS 40
D. RESULTS 42
i. PARTICIPANT CHARACTERISTICS 42
ii. SMV INFECTION 43
iii. SMV ILLNESS 43
iv. IMMUNE RESPONSE AGAINST SMV 44
v. PRE-CHALLENGE PREDICTORS OF ILLNESS 45
vi. DIFFERENCES BETWEEN INFECTED AND UNINFECTED SUBJECTS OVER TIME 46
E. DISCUSSION 48
i. PRE-CHALLENGE HBGA-BLOCKING ANTIBODY TITER AS CORRELATE OF PROTECTION 49
ii. TEMPORAL CHANGES IN SMV-SPECIFIC IMMUNOGLOBULINS AND HBGA-BLOCKING ANTIBODIES 50
iii. STRENGTHS AND LIMITATIONS 52
F. REFERENCES 54
G. TABLES 64
H. FIGURES 74
CHAPTER III: SUMMARY, GLOBAL HEALTH IMPLICATIONS, FUTURE DIRECTIONS 78
A. SUMMARY 78
B. GLOBAL HEALTH IMPLICATIONS 79
C. FUTURE DIRECTIONS 82
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