Research Article: Vaccination with whole-cell killed or recombinant leishmanial protein and toll-like receptor agonists against Leishmania tropica in BALB/c mice

Date Published: September 24, 2018

Publisher: Public Library of Science

Author(s): Mosayeb Rostamian, Fariborz Bahrami, Hamid M. Niknam, Humberto Lanz-Mendoza.

http://doi.org/10.1371/journal.pone.0204491

Abstract

One strategy to control leishmaniasis is vaccination with potent antigens alongside suitable adjuvants. The use of toll-like receptor (TLR) agonists as adjuvants is a promising approach in Leishmania vaccine research. Leishmania (L.) tropica is among the less-investigated Leishmania species and a causative agent of cutaneous and sometimes visceral leishmaniasis with no approved vaccine against it. In the present study, we assessed the adjuvant effects of a TLR4 agonist, monophosphoryl lipid A (MPL) and a TLR7/8 agonist, R848 beside two different types of Leishmania vaccine candidates; namely, whole-cell soluble L. tropica antigen (SLA) and recombinant L. tropica stress-inducible protein-1 (LtSTI1). BALB/c mice were vaccinated three times by the antigens (SLA or LtSTI1) with MPL or R848 and then were challenged by L. tropica. Delayed-type hypersensitivity (DTH), parasite load, disease progression and cytokines (IL-10 and IFN-γ) responses were assessed. In general compared to SLA, application of LtSTI1 resulted in higher DTH, higher IFN-γ response and lower lymph node parasite load. Also compared to R848, MPL as an adjuvant resulted in higher DTH and lower lymph node parasite load. Although, no outstanding ability for SLA and R848 in evoking immune responses of BALB/c mice against L. tropica infection could be observed, our data suggest that LtSTI1 and MPL have a better potential to control L. tropica infection and could be pursued for the development of effective vaccination strategies.

Partial Text

Leishmaniases are members of the neglected tropical diseases (NTDs), caused by intracellular protozoans of Leishmania genus which are transmitted via phlebotomine sand fly bites. There are three main forms of leishmaniases: visceral, cutaneous, and mucocutaneous. Approximately 350 million people live in areas with risk of leishmaniases in 98 countries. The disease affects 12 million people and its incidence is approximately two million cases per year [1]. Leishmania tropica is among the less-known Leishmania species which causes cutaneous leishmaniasis (CL) and rarely, visceral leishmaniasis (VL) in many endemic regions of the world [2]. Few studies have so far been dedicated to the pathology of L. tropica and the host immune responses against this parasite. Interestingly, the observed pathology of L. tropica in humans and experimental models is different from all other well-known Leishmania species, such as L. major [3]. These issues call for further studies on this source of a major public health problem, even more urgently.

In the present study for the first time, a homologous protein of LmSTI1 was identified in L. tropica and was produced recombinantly. Sequence analyses showed a high homology between LmSti1 and LtSti1, indicating that this region is conserved between the two Leishmania species. The LtSTI1 protein was successfully produced in an Escherichia coli expression system and was applied as single protein vaccine candidate.

To our best knowledge, this is the first report on immunization formulations against L. tropica, composed of the parasite’s whole-cell killed antigens (SLA) or its recombinant protein (LtSTI1) antigen, used with MPL and R848 adjuvants. We successfully prepared the SLA and also isolated, cloned, expressed and purified LtSTI1 and applied their combinations as vaccine candidates against L. tropica infection in a BALB/c mice model of infection. Our data indicate that MPL, in contrast to R848, was more effective with the antigens to evoke immune responses and it specifically worked better with LtSTI1 to evoke DTH.

 

Source:

http://doi.org/10.1371/journal.pone.0204491

 

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