Monoclonal Antibodies against Vibrio vulnificus RtxA1 Elicit Protective Immunity through Distinct Mechanisms SCIE SCOPUS

Cited 9 time in WEB OF SCIENCE Cited 9 time in Scopus
Title
Monoclonal Antibodies against Vibrio vulnificus RtxA1 Elicit Protective Immunity through Distinct Mechanisms
Author(s)
Lee, Tae Hee; Cha, Sun-Shin; Lee, Chang-Seop; Rhee, Joon Haeng; Chung, Kyung Min
Publication Year
2014-11
Abstract
Vibrio vulnificus causes rapidly progressing septicemia with an extremely high mortality rate (>= 50%), even with aggressive antibiotic treatment. The bacteria secrete multifunctional autoprocessing repeats-in-toxin (MARTX) toxins, which are involved in the pathogenesis of Gram-negative Vibrio species. Recently, we reported that immunization with the C-terminal region of V. vulnificus RtxA1/MARTXVv, RtxA1-C, elicits a protective immune response against V. vulnificus through a poorly defined mechanism. In this study, we generated a panel of new monoclonal antibodies (MAbs) against V. vulnificus RtxA1-C and investigated their protective efficacies and mechanisms in a mouse model of infection. Prophylactic administration of seven MAbs strongly protected mice against lethal V. vulnificus infection (more than 90% survival). Moreover, three of these MAbs (21RA, 24RA, and 47RA) demonstrated marked efficacy as postexposure therapy. Notably, 21RA was therapeutically effective against lethal V. vulnificus infection by a variety of routes. Using Fab fragments and a neutropenic mouse model, we showed that 21RA and 24RA mediate protection from V. vulnificus infection through an Fc-independent and/or neutrophil-independent pathway. In contrast, 47RA-mediated protection was dependent on its Fc region and was reduced to 50% in neutropenic mice compared with 21RA-mediated and 24RA-mediated protection. Bacteriological study indicated that 21RA appears to enhance the clearance of V. vulnificus from the blood. Overall, these studies suggest that humoral immunity controls V. vulnificus infection through at least two different mechanisms. Furthermore, our panel of MAbs could provide attractive candidates for the further development of immunoprophylaxis/therapeutics and other therapies against V. vulnificus that target the MARTX toxin.
ISSN
0019-9567
URI
https://sciwatch.kiost.ac.kr/handle/2020.kiost/2689
DOI
10.1128/IAI.02130-14
Bibliographic Citation
INFECTION AND IMMUNITY, v.82, no.11, pp.4813 - 4823, 2014
Publisher
AMER SOC MICROBIOLOGY
Subject
CAPSULAR POLYSACCHARIDE; CONJUGATE VACCINES; SURVIVAL FACTOR; COASTAL WATERS; TARGET-CELLS; IN-VITRO; INFECTION; TOXIN; IRON; PATHOGENESIS
Type
Article
Language
English
Document Type
Article
Publisher
AMER SOC MICROBIOLOGY
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