Antibody in Lymphocyte Supernatant (ALS) responses after oral vaccination with live Shigella sonnei vaccine candidates WRSs2 and WRSs3 and correlation with serum antibodies, ASCs, fecal IgA and shedding

The levels of antigen-specific Antibodies in Lymphocyte Supernatant (ALS) using an ELISA are being used to evaluate mucosal immune responses as an alternate to measuring the number of Antibody Secreting Cells (ASCs) using an ELISpot assay. A recently completed trial of two novel S. sonnei live oral...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2021-11, Vol.16 (11), p.e0259361
Main Authors: Venkatesan, Malabi M, Ballou, Cassandra, Barnoy, Shoshana, McNeal, Monica, El-Khorazaty, Jill, Frenck, Robert, Baqar, Shahida
Format: Article
Language:English
Subjects:
Analysis
Antibodies
Antibody-Producing Cells
Antigens
Assaying
Biology and Life Sciences
Correlation
Diarrhea
Drug dosages
Enzyme-linked immunosorbent assay
Evaluation
Feces
Health aspects
Hospitals
Immune response
Immunogenicity
Immunoglobulin A
Immunoglobulin G
Immunology
Infectious diseases
Investigations
Leukocytes, Mononuclear
Lipopolysaccharides
Lymphocytes
Medicine and Health Sciences
Mucosal immunity
Pediatrics
Peripheral blood mononuclear cells
Research and Analysis Methods
Shedding
Shigella
Shigella sonnei
Shigella Vaccines
Software
Vaccination
Vaccines
Viral antibodies
Virulence
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The levels of antigen-specific Antibodies in Lymphocyte Supernatant (ALS) using an ELISA are being used to evaluate mucosal immune responses as an alternate to measuring the number of Antibody Secreting Cells (ASCs) using an ELISpot assay. A recently completed trial of two novel S. sonnei live oral vaccine candidates WRSs2 and WRSs3 established that both candidates were safe, well tolerated and immunogenic in a vaccine dose-dependent manner. Previously, mucosal immune responses were measured by assaying IgA- and IgG-ASC in peripheral blood mononuclear cells (PBMCs). In this report, the magnitude of the S. sonnei antigen-specific IgA- and IgG-ALS responses was measured and correlated with previously described ASCs, serum antibodies, fecal IgA and vaccine shedding. Overall, the magnitude of S. sonnei anti-Invaplex50 ALS was higher than that of LPS or IpaB, and both vaccines demonstrated a more robust IgA-ALS response than IgG; however, compared to WRSs3, the magnitude and percentage of responders were higher among WRSs2 recipients for IgA- or IgG-ALS. All WRSs2 vaccinees at the two highest doses responded for LPS and Invaplex50-specific IgA-ALS and 63-100% for WRSs3 vaccinees responded. Regardless of the vaccine candidate, vaccine dose or detecting antigen, the kinetics of ALS responses were similar peaking on days 7 to 9 and returning to baseline by day 14. The ALS responses were vaccine-specific since no responses were detected among placebo recipients at any time. A strong correlation and agreement between responders/non-responders were noted between ALS and other mucosal (ASC and fecal IgA) and systemic (serum antibody) immune responses. These data indicate that the ALS assay can be a useful tool to evaluate mucosal responses to oral vaccination, an observation noted with trials of other bacterial diarrheal pathogens. Furthermore, this data will guide the list of immunological assays to be conducted for efficacy trials in different populations. It is hoped that an antigen-specific-ALS titer may be a key mucosal correlate of protection, a feature not currently available for any Shigella vaccines candidates. https://clinicaltrials.gov/show/NCT01336699.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0259361