Department of Epidemiology of Microbial Diseases; Yale School of Public Health, New Haven, United States; Gonçalo Moniz Institute, Oswaldo Cruz Foundation; Brazilian Ministry of Health, Salvador, Brazil
Haritha Adhikarla
Department of Epidemiology of Microbial Diseases; Yale School of Public Health, New Haven, United States
Camila Hamond
Department of Epidemiology of Microbial Diseases; Yale School of Public Health, New Haven, United States
Department of Medicine, Division of Infectious Disease; University of California Irvine, Irvine, United States
Camila B Rodrigues
Department of Medicine, Division of Infectious Disease; University of California Irvine, Irvine, United States; Institute of Technology in Immunobiology, Oswaldo Cruz Foundation; Brazilian Ministry of Health, Rio de Janeiro, Brazil
Vimla Bisht
Department of Epidemiology of Microbial Diseases; Yale School of Public Health, New Haven, United States
Jarlath E Nally
Infectious Bacterial Diseases Research Unit, National Animal Disease Center, Agricultural Research Service; United States Department of Agriculture, Ames, United States
David P Alt
Infectious Bacterial Diseases Research Unit, National Animal Disease Center, Agricultural Research Service; United States Department of Agriculture, Ames, United States
Mitermayer G Reis
Gonçalo Moniz Institute, Oswaldo Cruz Foundation; Brazilian Ministry of Health, Salvador, Brazil
Peter J Diggle
CHICAS, Lancaster Medical School; Lancaster University, Lancaster, United Kingdom
Philip L Felgner
Department of Medicine, Division of Infectious Disease; University of California Irvine, Irvine, United States
Department of Epidemiology of Microbial Diseases; Yale School of Public Health, New Haven, United States; Gonçalo Moniz Institute, Oswaldo Cruz Foundation; Brazilian Ministry of Health, Salvador, Brazil
Leptospirosis is the leading zoonotic disease in terms of morbidity and mortality worldwide. Effective prevention is urgently needed as the drivers of disease transmission continue to intensify. The key challenge has been developing a widely applicable vaccine that protects against the >300 serovars that can cause leptospirosis. Live attenuated mutants are enticing vaccine candidates and poorly explored in the field. We evaluated a recently characterized motility-deficient mutant lacking the expression of a flagellar protein, FcpA. Although the fcpA- mutant has lost its ability to cause disease, transient bacteremia was observed. In two animal models, immunization with a single dose of the fcpA- mutant was sufficient to induce a robust anti-protein antibodies response that promoted protection against infection with different pathogenic Leptospira species. Furthermore, characterization of the immune response identified a small repertoire of biologically relevant proteins that are highly conserved among pathogenic Leptospira species and potential correlates of cross-protective immunity.
