HbR: What’s So Unique?
Being in the cell membrane, HbR is not only a gateway for haemoglobin to enter, but also acts as an important enzyme in the glucose-breaking pathway in the cells, notes Mukhopadhyay. His group took advantage of this versatile molecule and designed two forms of a DNA construct that codes this protein. They used a vector DNA, which acts as a vehicle to carry this vaccine DNA into the body.
However, to check whether this DNA is immunogenic, ie., if it is an antigen, the group has tested it against the blood sera of patients. Antigens should evoke the body’s immune system to produce antibodies, specific against HbR. “…we have found antibodies against HbR in the kala-azar patient serum. This not only boosts our finding that HbR is [a] better candidate as vaccine against Leishmaniasis, but also as a promising diagnostic marker,” says Mukhopadhyay.
Either the full DNA that codes the protein can be immunogenic, which means it can provoke an immune response, or specific regions in them (epitopes) can be immunogenic. The group found that both the full length DNA (HbR-FL DNA), and the portion of DNA that codes the N-terminal portion of the HbR (HbR-N DNA) can provoke an immune response. To study the immunizing effect and efficacy, the group used specific mice and hamsters that are models for VL. After 21 days of infection by L. donovani¸ the Leishmania species that causes VL, they injected the above two types of DNA.
Their observations showed that the infected liver and spleens are swollen, and in the immunized animals (using the two DNA types), by the eighth month, the organs have restored to normal sizes. “…vaccination with both HbR-DNA constructs inhibits more than 99% splenic and hepatic parasite burden [in the infected animals, compared to the controls]” says Mukhopadhyay. However, compared to HbR-FL, HbR-N is more efficient.
HbR and Leishmaniasis: The Future
At the cellular level, the authors have observed the desired evocation of TH1 responses. At the end of the study, they also found that the inflammatory cytokines are fewer. Moreover, they report that immune “complement mediated system” destroys the parasite within the cells. Thus, they give a clue that this action leaves an “immune memory” in the body.
In the clinic, then the question is, “will patients need a booster dose?” Mukhopadhyay tells us that “…patients are usually protected from recurrent infection possibly due [to] the presence of some antibodies against parasites elicited during first infection,” but did not give a direct Yes or No. Perhaps it is too early to say. However, he does tell us, “HbR not only evokes protective Th1-response without any adjuvant but also suppresses disease promoting cytokines to confer complete protection.”
Can this vaccine candidate be useful for other types of Leishmania? Perhaps. Mukhopadhyay says, “HbR is conserved across Leishmania species and hence could also be [a] potential candidate against different forms of leishmaniasis.” Having filed a patent on this potential vaccine, Mukhopadhyay says, “we would like to see how government funding agencies will take it further… it is beyond the capacity of an individual laboratory investigator/s, requires extensive funding.” Either way, this study seems to be a ray of hope to treat Leishmaniasis. Only the future will show the long-term benefits.
Guha, R., Gupta, D., Rastogi, R., Vikram, R., Krishnamurthy, G., Bimal, S., Roy, S.and Mukhopadhyay, A. Vaccination with Leishmania Hemoglobin Receptor–Encoding DNA Protects Against Visceral Leishmaniasis. (2013). Science Translational Medicine. Accessed September 11, 2013.
World Health Organization. Leishmaniasis. (2013). Accessed September 11, 2013.
Clinical Trials. LEISH-F3 + GLA-SE and the LEISH-F3 + MPL-SE Vaccine. (2013). Accessed September 11, 2013.
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