Antibody secreting B cells and plasma antibody response to rotavirus vaccination in infants from Kolkata India

Anuradha Sinha,Suman Kanungo,Deok Ryun Kim,Byomkesh Manna,Manki Song,Ju Yeon Park,Bisakha Haldar,Prashant Sharma,Aiyel Haque Mallick,Soon Ae Kim,Sudhir Babji,Dipika Sur,Gagandeep Kang,Mohammad Ali,William A Petri Jr,Thomas F Wierzba,Cecil Czerkinsky,Ranjan Kumar Nandy,Ayan Dey

doi:10.1016/j.heliyon.2018.e00519

Abstract

BackgroundAssessing immune response after rotavirus vaccination consists in measuring serum or plasma IgA and IgG antibodies, but these assays provide very little information about the mucosal immune response. Thus the development of assays for detection of mucosal immune response following rotavirus vaccination is essential. We evaluate to assess circulating antibody-secreting cells (ASCs) as a potential means to evaluate mucosal immune responses to rotavirus vaccine. Methods372 subjects, aged 6 weeks, were enrolled in the study. All the subjects were assigned to receive two doses of Rotarix® vaccine. Using a micro-modified whole blood-based ELISPOT assay, circulating rotavirus type-specific IgA- and IgG-ASCs, including gut homing β7+ ASCs, were enumerated on week 6 before the first dose of Rotarix vaccination at 7 weeks of age and week 18 after the second vaccination at 17 weeks of age. Plasma samples collected before vaccination, and after two doses of Rotarix® vaccination were tested for plasma rotavirus IgA titers. ResultsTwo doses of Rotarix® provided to induce sero-protective titer of ≥ 20 Units in 35% of subjects. Total blood IgA- ASC responses were detected in 26.4% of subjects who were non-responder before vaccination. Among responders, 47% of the subjects also have sero-protective plasma IgA titers. DiscussionOur results suggest that virus-specific blood gut homing ASCs were detected and provide insight into mucosal immune response after rotavirus vaccination. Further studies are needed to evaluate the duration of such immune responses and to assess the programmatic utility of this whole blood-based mucosal ASC testing for the rotavirus immunization program.

Highlights

One out of ten children below 5 years of age dies due to diarrheal diseases, resulting in 800,000 fatalities annually
The study was approved by the Indian Council of Medical Research (ICMR), Health Ministry's Screening Committee (HMSC), Government of India; the Institutional Ethical Committee at National Institute of Cholera and Enteric Disease (NICED) and the Institutional Review Boards of International Vaccine Institute (IVI), South Korea; University of Virginia and University of Vermont USA
While a previous study has explored the induction of gut homing α4β7+ cells following natural rotavirus infection in children [27], we examined the role of antigen-specific antibody-secreting cells (ASCs) including gut-homing ASCs following RV vaccination in humans

Summary

Introduction

One out of ten children below 5 years of age dies due to diarrheal diseases, resulting in 800,000 fatalities annually. Most deaths occur in sub-Saharan Africa and South Asia Among these deaths, rotavirus (RV) is the leading cause of severe gastroenteritis and is responsible for 215,000 deaths per year with most of the deaths occur in developing countries [1]. Mucosal immunity is considered to provide protection from RV entry and replication. Assessing immune response after rotavirus vaccination consists in measuring serum or plasma IgA and IgG antibodies, but these assays provide very little information about the mucosal immune response. The development of assays for detection of mucosal immune response following rotavirus vaccination is essential. We evaluate to assess circulating antibody-secreting cells (ASCs) as a potential means to evaluate mucosal immune responses to rotavirus vaccine.

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