Heterologous DNA prime-protein boost immunization with RecA and FliD offers cross-clade protection against leptospiral infection

The emergence of >300 serovars of Leptospira confounded the use of generalized bacterin, the whole cell lysate, as vaccines to control leptospirosis. Because of substantial genetic and geographic heterogeneity among circulating serovars, one vaccine strain per serovar cannot be efficacious agains...

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Bibliographic Details
Published in:Scientific reports 2018-04, Vol.8 (1), p.6447-9, Article 6447
Main Authors: Raja, Veerapandian, Sobana, Sankaran, Mercy, Charles Solomon Akino, Cotto, Bianca, Bora, Durlav Prasad, Natarajaseenivasan, Kalimuthusamy
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - pharmacology
Animals
Antibody Formation
Bacterial Proteins - immunology
Bacterial Proteins - metabolism
Cricetinae
Cross Protection
Deoxyribonucleic acid
DNA
DNA vaccines
Epitopes
Epitopes - immunology
Flagella
Immune response (humoral)
Immunity, Cellular - immunology
Immunity, Heterologous - immunology
Immunization, Secondary - methods
Immunogenicity
Leptospira
Leptospira - genetics
Leptospira - immunology
Leptospirosis
Leptospirosis - immunology
Leptospirosis - prevention & control
Lymphocytes B
Lymphocytes T
Proteins
Rec A Recombinases - immunology
Rec A Recombinases - metabolism
RecA protein
Recombinant Proteins - immunology
Recombinase
Vaccination - methods
Vaccines
Vaccines, DNA - genetics
Vaccines, DNA - immunology
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Summary:The emergence of >300 serovars of Leptospira confounded the use of generalized bacterin, the whole cell lysate, as vaccines to control leptospirosis. Because of substantial genetic and geographic heterogeneity among circulating serovars, one vaccine strain per serovar cannot be efficacious against all the serovars. We have performed heterologous DNA prime-protein boost vaccination challenge studies in hamsters using in vivo expressed, leptospiral recombinase A (RecA) and flagellar hook associated protein (FliD). We prepared the monovalent recombinant protein, plasmid DNA, and DNA prime protein boost adjuvant vaccines. The whole cell bacterin served as a control. Our data show that (i) RecA and FliD have multiple immunogenic B and T-cell epitopes with highly conserved domains among most prevalent pathogenic Leptospira spp., (ii) humoral and cell mediated immune responses were induced remarkably, (iii) provides significant protection against homologous (Autumnalis strain N2) and cross-clade heterologous (Canicola strain PAI-1) challenge infection for the heterologous prime-protein boost (∼91-100%) and, the DNA vaccine (∼75-83%). Recombinant protein vaccine shows only partial protection (∼58-66%), (iv) RecA prime-protein boost vaccine shows sterilizing immunity, with heterologous protection. This RecA/FliD prime-protein boost strategy holds potential for vaccination against animal leptospirosis and for a better control of zoonotic transmission.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-24674-8