Research Projects

Leptospirosis is a spirochaetal, potentially fatal zoonosis of ubiquitous distribution which possesses a broad host range affecting almost all mammals. Leptospirosis causes huge economic burden to animal husbandry due to reproductive losses ranging from abortion, still birth, early embryonic death, agalactia and infertility in farm animals. Leptospira vaccines available at present are inactivated whole cell bacterins prepared from pathogenic Leptospira spp. Although protective against lethal infection, bacterin-induced immunity is considered short term requiring vaccine administration biannually. Besides, bacterin-based vaccine cause serious side effects due the presence of both LPS and residual media components. Further, these vaccines provide serovar-specific protection and provide little cross protection against infection with other leptospiral serovars The shortcomings of bacterin based leptospiral vaccines has led researchers to explore the feasibility of Outer membrane proteins (OMPs) which are found ubiquitously across all pathogenic Leptospira serovars as attractive alternatives to bacterin based vaccines. Leptospira immunoglobulin-like proteins (LigA & LigB) which are sero-diagnostic markers for acute phase leptospirosis are the most attractive subunit vaccine candidates. Hence, a multi-epitope chimeric vaccine construct was designed using immunoinformatics approaches utilizing the immunogenic epitopes of both LigA and LigB proteins was chosen as the vaccine antigen. Additionally, an adjuvant, the mycobacterial heparin-binding hemagglutinin adhesin (HBHA), was incorporated into the final multi-epitope vaccine construct using a suitable linker. The vaccine construct developed was found to interact with Toll-like receptor 4 (TLR4) using molecular docking. A recent study involving the use of E. coli Cytolysin (ClyA) based Polymerized Porin (PP) as a novel delivery platform for coronavirus vaccine revealed that multimerization of Receptor binding domain (RBD) of SARS-CoV-2 using RBD-ClyA:PP nanoscaffold vaccine showed better immune-protective ability against SARS-CoV-2 than RBD monomer. RBD-ClyA:PP induced higher neutralizing antibody production than RBD monomers as they display more spatial conformational epitopes. Antigens presented to the immune system at high densities (Antigen multimerization) by PP based nanovaccine led to the activation of low-affinity B cells. Moreover, it was revealed that RBD-ClyA:PP increased the effectiveness of lymph node targeting of RBD antigens and stimulated antigen uptake, processing & presentation by Dendritic cells in-vivo than monomeric RBD antigen. This novel delivery platform has not been investigated for its utility as a nanoscaffold vaccine for leptospirosis. Hence, the investigators of this research project intend to utilize Cytolysin based Polymerized Porin (ClyA:PP) as a nanoscaffold vaccine for surface display of Multi-epitope Chimeric Protein (MECP) generated using LigA and LigB epitopes.