In Depth Breadth Analyses of Human Blockade Responses to Norovirus and Response to Vaccination.

Joel Haynes,Virginia Perry,Ralph Braun,Heather Watkins,Evelyn Benson,Alisa Meeks,Gayle Watts

doi:10.3390/v11050392

Abstract

To evaluate and understand the efficacy of vaccine candidates, supportive immunological measures are needed. Critical attributes for a norovirus vaccine are the strength and breadth of antibody responses against the many different genotypes. In the absence of suitable neutralization assays to test samples from vaccine clinical trials, blockade assays offer a method that can measure functional antibodies specific for many of the different norovirus strains. This paper describes development and optimization of blockade assays for an extended panel of 20 different norovirus strains that can provide robust and reliable data needed for vaccine assessment. The blockade assays were used to test a panel of human clinical samples taken before and after vaccination with the Takeda TAK-214 norovirus vaccine. Great variability was evident in the repertoire of blocking antibody responses prevaccination and postvaccination among individuals. Following vaccination with TAK-214, blocking antibody levels were enhanced across a wide spectrum of different genotypes. The results indicate that adults may have multiple exposures to norovirus and that the magnitude and breadth of the complex preexisting antibody response can be boosted and expanded by vaccination.

Highlights

Noroviruses are a highly prevalent pathogen associated with approximately 20% of diarrheal disease worldwide and are responsible for greater than 200,000 deaths each year [1,2,3]
Previous development of a GII.4 (2012) Sydney blockade assay in our laboratory had identified several parameters that greatly improved the measurement of blocking antibodies
As more virus-like particles (VLPs) were generated for use in the blockade assay panel, several VLPs were found not to work well in the conditions used for the GII.4 (2012) assay

Summary

Introduction

Noroviruses are a highly prevalent pathogen associated with approximately 20% of diarrheal disease worldwide and are responsible for greater than 200,000 deaths each year [1,2,3]. All age groups are susceptible to infection; the greatest incidence of disease occurs in children under the age of 5 years that can cause up to 70,000 deaths in children in developing countries. In addition to the effect on individual health, the worldwide economic burden of norovirus disease is estimated to be approximately 60 billion dollars per year [5]. As the understanding of the prevalence and burden of norovirus disease strengthens, the need for preventative and therapeutic measures becomes more apparent, including the development of an effective vaccine [6,7]

Methods

Results

Conclusion