Final published version
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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - A live attenuated-vaccine model confers cross-protective immunity against different species of the leptospira genus
AU - Wunder, E.A.
AU - Adhikarla, H.
AU - Hamond, C.
AU - Bonner, K.A.O.
AU - Liang, L.
AU - Rodrigues, C.B.
AU - Bisht, V.
AU - Nally, J.E.
AU - Alt, D.P.
AU - Reis, M.G.
AU - Diggle, P.J.
AU - Felgner, P.L.
AU - Ko, A.
PY - 2021/1/26
Y1 - 2021/1/26
N2 - 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. © 2021, eLife Sciences Publications Ltd. All rights reserved.
AB - 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. © 2021, eLife Sciences Publications Ltd. All rights reserved.
U2 - 10.7554/ELIFE.64166
DO - 10.7554/ELIFE.64166
M3 - Journal article
VL - 10
SP - 1
EP - 20
JO - eLife
JF - eLife
SN - 2050-084X
ER -