Gandhinagar team takes initial steps to develop a vaccine for leptospirosis

A key peptide that can be used to develop a new preventive vaccine against leptospirosis has been successfully identified by researchers from the Gujarat Biotechnology Research Centre, Gandhinagar. Leptospirosis is an emerging tropical infectious disease, and currently there is no preventive vaccine for humans that is available in the market. The researchers used computer-based analysis to study the whole protein set of the bacteria Leptospira interrogans and narrowed the search down to one effective immunogenic protein. This protein was found to be present in almost all the serovars (different types within a species) of the bacteria and can be an effective vaccine candidate against most serovars.

Major killer

According to a paper published in 2015, leptospirosis causes almost 60,000 deaths every year, globally. The bacteria can be transmitted via exposure to contaminated water or soil or direct contact with reservoirs hosts like wild or domestic animals.

The proteome (entire protein set) of a serovar Copenhageni strain was studied using bioinformatics (computational biology analysis) approach. “We looked at all the 3,654 proteins in the bacteria with the help of several advanced computational methods and predicted the antigenicity — ability to bind to the antibody present on B cells for inducing immune response,” explains Swapnil Kumar, a Junior Research Fellow at the centre and an author of the paper published recently in Scientific Reports. “Extensive analysis helped us narrow down to 21 proteins which had high antigenicity score.”

Membrane proteins

Among these proteins, the researchers further searched to identify the outer membrane proteins as these are known to play important roles in the interaction between the bacteria and their host. Further computational modelling and simulation helped the researchers narrow it to one specific protein. The protein was chosen as the candidate immunogen once the physicochemical and structural studies were carried out.

The researchers then looked for sites on human T cells and B cells where the antigen could bind. Identification of target sites is a key step in vaccine design. “We looked at the surface of the cells, their flexibility, affinity to water and identified regions or peptide sequences that could bind to our peptide vaccine and give a long lasting immune response,” explains Dr. Jayashankar Das, the corresponding author of the paper.

“We have to carry out proteomic and genomic study for different strains of the bacteria followed by in vitro validation of the identified key proteins,” he adds. The group is also working on high throughput genomic analysis for the development of an on-site diagnostic kit.