A live attenuated-vaccine model confers cross-protective immunity against different species of the Leptospira genus

eLife

Katharine A Owers Bonner¹  Camila Hamond²  Philip L Felgner³  Jarlath E Nally⁴  Camila B Rodrigues⁴  Mitermayer G Reis⁴  Haritha Adhikarla⁴  Vimla Bisht⁵  Elsio A Wunder⁵  David P Alt⁵  Li Liang⁵  Albert Ko⁶  Peter J Diggle⁶ 

[1] Brazilian Ministry of Health, Salvador, Brazil;Gonçalo Moniz Institute, Oswaldo Cruz Foundation;University of California Irvine, Irvine, United States;Yale School of Public Health, New Haven, United States;Department of Epidemiology of Microbial Diseases;Department of Medicine, Division of Infectious Disease;

关键词: leptospira;    live attenuated vaccine;    leptospirosis;    cross-protective immunity;   

DOI  :  10.7554/eLife.64166

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown