Date Published: January 8, 2015
Publisher: Public Library of Science
Author(s): Luzinei da Silva-Couto, Raquel Peralva Ribeiro-Romão, Andrea Franco Saavedra, Beatriz Lilian da Silva Costa Souza, Otacílio Cruz Moreira, Adriano Gomes-Silva, Bartira Rossi-Bergmann, Alda Maria Da-Cruz, Eduardo Fonseca Pinto, David Joseph Diemert. http://doi.org/10.1371/journal.pntd.0003439
Abstract: BackgroundPrevious results have shown that oral and intranasal administration of particulate Leishmania (Leishmania) amazonensis antigens (LaAg) partially protects mice against L. amazonensis infection. However, vaccination studies on species of the subgenus Viannia, the main causative agent of cutaneous and mucosal leishmaniasis in the Americas, have been hampered by the lack of easy-to-handle bio-models that accurately mimic the human disease. Recently, we demonstrated that the golden hamster is an appropriate model for studying the immunopathogenesis of cutaneous leishmaniasis caused by L. (Viannia) braziliensis. Using the golden hamster model, our current study investigated whether the protective effect of intranasal immunisation with LaAg can be extended to L. braziliensis infection.Methodology/Principal FindingsGolden hamsters vaccinated with either two intranasal (IN) doses of LaAg (10 µg) or two intramuscular doses of LaAg (20 µg) were challenged 2 weeks post-vaccination with L. braziliensis. The results showed that IN immunisation with LaAg significantly reduced lesion growth and parasitic load as well as serum IgG and IgG2 levels. At the experimental endpoint on day 114 post-infection, IN-immunised hamsters that were considered protected expressed IFN-γ and IL10 mRNA levels that returned to uninfected skin levels. In contrast to the nasal route, intramuscular (IM) immunisation failed to provide protection.Conclusions/SignificanceThese results demonstrate for the first time that the nasal route of immunisation can induce cross protection against L. braziliensis infection.
Partial Text: Leishmaniasis is a neglected disease caused by intracellular protozoan parasites of the genus Leishmania spp, with a wide spectrum of clinical manifestations ranging from chronic cutaneous ulcers to fatal visceral disease. L. (Viannia) braziliensis is the most prevalent species associated with American tegumentary leishmaniasis (ATL), which constitutes a serious public health problem affecting 28,000 people annually in Brazil . Despite the advent of new anti-leishmanial compounds , multiple injections of pentavalent antimonials, which invariably produce serious toxic side effects, still remain the first-line therapy for all forms of the disease. The problem is further aggravated by therapeutic failure along with the emergence of antimonial resistance .
The majority of studies aimed at developing an effective Leishmania spp vaccine have been conducted for experimental CL caused mainly by L. major or L. amazonensis. L. braziliensis, which is the main causative agent of cutaneous and mucosal leishmaniasis in the Americas, has been largely neglected in the context of vaccine development mainly due to the unsuitability of the mouse model. Moreover, candidate antigens – such as the leishmanial homologue of receptors for activated C kinase protein (LACK), thiol-specific antioxidant (TSA), Leishmania spp elongation and initiation factor (LeIF) and L. major stress-inducible protein 1 (LmST1) – all of which induced protection against L. major, failed to prevent L. braziliensis infection in mice .