Evaluation of the safety and immunogenicity of the oral inactivated multivalent enterotoxigenic Escherichia coli vaccine ETVAX in Bangladeshi adults in a double-blind, randomized, placebo-controlled Phase I trial using electrochemiluminescence and ELISA assays for immunogenicity analyses

Autor: Firdausi Qadri, Marjahan Akhtar, Nicole Maier, Tasnuva Ahmed, Ann-Mari Svennerholm, Tanzeem Ahmed Rafique, Joanna Kaim, Anna Lundgren, Nils Carlin, Farhana Khanam, A. Louis Bourgeois, Mohiul I. Chowdhury, Arifuzzaman Khan, Yasmin Ara Begum, Alan Fix, Thomas F. Wierzba, Taufiqur Rahman Bhuiyan, Richard I. Walker, Mir Z. Sharif, Laila N. Islam, Sadia Isfat Ara Rahman
Rok vydání: 2019
Předmět:
SIgA
secretory IgA
Male
LCTBA
CTB/LTB hybrid protein
medicine.medical_treatment
Lymphocyte
ETEC
enterotoxigenic Escherichia coli
medicine.disease_cause
AEs
adverse events
Antibodies in lymphocyte supernatant
Immunogenicity
Vaccine
0302 clinical medicine
ECL
electrochemiluminescence
Enterotoxigenic Escherichia coli
030212 general & internal medicine
Escherichia coli Infections
Bangladesh
Antibody-secreting cell
biology
Escherichia coli Vaccines
Immunogenicity
Toxoid
Middle Aged
LT
heat labile toxin
Antibodies
Bacterial
ALS
antibodies in lymphocyte supernatant
Infectious Diseases
medicine.anatomical_structure
MSD
Meso Scale Discovery
PBMC
peripheral blood mononuclear cells
Molecular Medicine
ELISA
Female
CFs
colonization factors
Antibody
Adjuvant
IgA
Adult
dmLT
double mutant heat labile toxin
Adolescent
030231 tropical medicine
Enzyme-Linked Immunosorbent Assay
Placebo
Article
Young Adult
03 medical and health sciences
Antigen
ASC
antibody-secreting cell
medicine
Humans
Electrochemiluminescence
SAE
serious adverse event
General Veterinary
General Immunology and Microbiology
ETEC
business.industry
Public Health
Environmental and Occupational Health
Electrochemical Techniques
ST
heat-stable toxin
Immunoglobulin A
CTB
cholera toxin B-subunit
Immunoglobulin G
Luminescent Measurements
Immunology
biology.protein
business
Vaccine
Zdroj: Vaccine
ISSN: 0264-410X
Popis: Highlights • The killed oral ETEC vaccine ETVAX ± dmLT adjuvant was safe in Bangladeshi adults. • All vaccinees responded to all 5 primary vaccine antigens in ALS specimens. • A majority of vaccinees responded to ≥4 antigens in plasma specimens. • A sensitive electrochemiluminescence assay was established for small sample volumes. • ALS responses measured by electrochemiluminescence and ELISA assays correlated well.
The safety and immunogenicity of the second generation oral enterotoxigenic Escherichia coli (ETEC) vaccine ETVAX, consisting of inactivated recombinant E. coli strains over-expressing the colonization factors (CFs) CFA/I, CS3, CS5 and CS6 and the heat labile toxoid LCTBA, were evaluated in Bangladeshi volunteers. To enable analysis of antibody responses against multiple vaccine antigens for subsequent use in small sample volumes from children, a sensitive electrochemiluminescence (ECL) assay for analysis of intestine-derived antibody-secreting cell responses using the antibodies in lymphocyte secretions (ALS) assay was established using Meso Scale Discovery technology. Three groups of Bangladeshi adults (n = 15 per group) received two oral doses of ETVAX with or without double mutant LT (dmLT) adjuvant or placebo in the initial part of a randomized, double-blind, placebo-controlled, age-descending, dose-escalation trial. CF- and LTB-specific ALS and plasma IgA responses were analyzed by ECL and/or ELISA. ETVAX was safe and well tolerated in the adults. Magnitudes of IgA ALS responses determined by ECL and ELISA correlated well (r = 0.85 to 0.98 for the five primary antigens, P
Databáze: OpenAIRE
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