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Fighting the old disease of Leptospirosis with new strategies

Leptospirosis, an infection caused by the bacterium belonging to the genus Leptospira, is a tricky disease. It is the most common disease spread by animals to humans (zoonotic disease) worldwide and is now re-emerging as a significant threat to us. It is responsible for over 1 million cases every year and 60,000 annual deaths worldwide. The causative bacterium is ubiquitous—found on land and in water. Although the disease can be prevented by practising good hygiene, sanitation and proper pasteurisation of milk, things that are easier said than done, prevention through a vaccine is now in vogue.

In a recent study, researchers from the Gujarat Biotechnology Research Centre (GBRC) Department of Science and Technology, Government of Gujarat, have developed ways to efficiently diagnose and prevent the disease through the development of a new vaccine. The study is published in Scientific Reports and is supported by Gujarat State Biotechnology Mission.

In humans, symptoms of Leptospirosis involve fever and severe back pain in mild cases, and renal and hepatic failure along with altered nervous system function in severe cases. “Leptospirosis is one of the diseases that badly affect the coastline of India including Gujarat. This is why the Gujarat Biotechnology Research Centre , with the support of the DST, Government of Gujarat, has taken the initiative to develop efficient diagnostics as well as a vaccine for this disease”, says Dr. Jayashankar Das, Principal Investigator and an author of the study, talking to Research Matters.

Although vaccinations have existed for leptospirosis, they offer only short-term protection. A significant issue with controlling the spread of the disease is that the organism has many different serovars (250 to be exact). A ‘serovar’ is a variant of an organism that differs by its immunogenic properties. Hence, our body reacts differently to two different serovars despite both of them being mild variations of the same organism. Since our body does not produce the same antibodies against the serovars, vaccination is a concern as currently available vaccines provide protection only for those serovars against which they have been specifically tailored, and no others. Thus, there is a crying need for a vaccine that can universally provide immunity against all the possible variants of the pathogen.

The researchers of this study have tried to design one such universal vaccine for leptospirosis based on the proteins present on the bacteria’s body. The outer coat of the bacterium is made up of many proteins called outer membrane proteins, which trigger the host’s immune response. Once the host body responds by mounting the defences, it eliminates the organism through the innate immune system. Thus, these proteins are said to be highly antigenic, which help in the production of antigens—proteins that can cause our body to produce antibodies in response.
A good antigen is required in every vaccine so that the human or animal it is administered to will produce antibodies and thereby build up immunity against said antigen. In the case of Leptospira, the outer membrane proteins are almost the same across many serovars. The researchers of the study have screened each of these proteins using immunoinformatics tools, and have identified the most antigenic proteins. This computer run programme was able to comb through the entire set of proteins that the most commonly used serovar (Leptospira interrogans serovar Copenhageni strain L1-130) is capable of producing in its lifetime. This set of predetermined proteins is called a ‘proteome’.

The researchers then identified and analyzed the most important part of the protein, called the epitope, which interacts with our cells triggering the immune response. A type of white blood cell in our body called the small lymphocytes or ‘T cells’, fits into the epitope like a Lego block, which is the first step in the immune response. The team of GBRC has modelled the structure of the epitope and the T cells with different Bioinformatics based modelling and simulation tools. They then tested if the modelled proteins would join together as it happens in nature, and trigger the cascade of immune responses.

Although the study has not immediately resulted in the production of a new and improved vaccine, the basic understanding of the interaction of proteins involved in the body’s immune response is an incredibly promising lead. The high throughput Bioinformatics and computational biology approach has helped to screen large number of proteins with a minimum human error and narrowed down to possible leads, which can save time in initial experiments in the laboratories.

The study is a big step towards identifying specific structures responsible for the success or failure of a vaccine, thus providing a direction for future research on vaccine development. In the Omics era, the advancement of high-throughput technologies, together has facilitated large-scale biological measurements and new discoveries in a multidisciplinary way. Also, this approach saves a lot of time in developing new therapeutic targets not just for leptospirosis but for other diseases as well.

Editors note : The story has been updated with a few corrections that were missed initially. We apologise for the confusion and regret the error.