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.