Taking the Bug by its Food, Blood: A Potential Vaccine for Leishmaniasis

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Home / Taking the Bug by its Food, Blood: A Potential Vaccine for Leishmaniasis
Comparison of normal, affected, and HbR-DNA-immunized (treated) liver and spleen of a hamster used in the study.

Comparison of normal, affected, and HbR-DNA-immunized (treated) liver and spleen of a hamster used in the study. Image courtesy of Amitabha Mukhopadhyay

Researchers from India have discovered a vaccine candidate against the black fever (kala-azar), taking advantage of the disease-causing parasite’s blood thirst.

The single-celled parasite, Leishmania, has many cousins that cause a variety of infectious diseases; leishmaniasis in humans and animals – under skin or in mucous layers or internal organs. The parasite invades backboned animals as promastigotes, i.e. with a flagellum, via blood-sucking insects like sandflies. Visceral Leishmania (VL), or kala-azar, is one of these many kinds caused by L. donovoni, and it affects liver and spleen, the primary military organs of the body.

Amitabha Mukhopadhyay, from the National Institute of Immunology, New Delhi, India, along with his colleagues at the Indian Institute of Chemical Biology, Kolkata, and Rajendra Memorial Research Institute of Medical Sciences, Patna, has designed a potential DNA vaccine that can arrest the activity of haemoglobin receptor (HbR), a cell membrane protein at the base of the parasite’s flagellum, that helps it suck and process the haemoglobin.

Leishmaniasis Vaccine: This Dangerous Disease Needs Preventative Measures

The scary news about VL is that it is fatal, and is the second most common insect-borne disease, after Malaria. “Leishmaniasis affects about 12 million people worldwide and 500,000 new cases are reported annually […and…] is compounded with co-infection in HIV patients” Mukhopadhyay told Decoded Science.

He adds that, “[it] has been identified as a category 1 disease by the World Health Organisation (WHO)”. The available resort now is chemotherapy using drugs like amphotericin B, but at the cost of the parasite’s resistance to them.

Leishmania invades the blood cells and impairs the immune system. The T-helper (TH) cells, a type of white blood cell (WBC) produce cytokines in varied levels as an immune response. Thanks to VL, the protective cytokines produced by TH1 cells, called IL-12 (Interleukin) and IFN-γ (Interferon) are not enough to fight the infection. Due to weak expression of the respective genes, these cytokines are not able to help the macrophages, to eat up the pathogens. On the other hand, TH2 cells produce more IL-4 and IL-10, resulting in inflammatory symptoms. In order to restore the immune response by TH1 cells, vaccines become the only hope.

A rational approach to search for a novel drug target against intracellular pathogens is the exploitation of biochemical differences between the parasite and its host” says Mukhopadhyay. From their past research, his group knows that HbR is the one differing between the host and the parasite, and it can be the vaccine target.

Some other scientists have attempted at designing vaccines, using other antigenic portions of the parasite. One example is the LEISH-F3+GLA-SE vaccine, which is under phase-I clinical trial, launched by the Infectious Diseases Research Institute (IDRI), Washington, USA, along with WHO, and funds from Bill and Melinda Gates Foundation. The team hopes that this might work, but there seems to be still room for improvement.

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