Intranasal Vaccination with Leishmanial Antigens Protects Golden Hamsters (Mesocricetus auratus) Against Leishmania (Viannia) braziliensis Infection

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.

Efficacy of intranasal LaAg vaccine against Leishmania amazonensis infection in partially resistant C57Bl/6 mice

“…Before clinical studies for vaccines, it is necessary to perform very robust pre-clinical studies using different infection models, such as mice, dog and non-human primates [ 36 ]. Intranasal LaAg vaccine is protective to BALB/c mice against L. amazonensis [ 21 ] and L. infantum / chagasi infection [ 23 ] and to hamsters against L. braziliensis [ 29 ]. LaAg ability to protect against different parasite species ( L. amazonensis , L. chagasi and L. braziliensis ) and positive results in two different species (BALB/c and Hamster) is very promising.…”

“…Moreover, production of IFN-gamma in the site of infection in BALB/c mice is associated with protection against L. amazonensis infection [ 24 ]. The mechanism of intranasal LaAg vaccine against L. amazonensis in BALB/c [ 21 ]; L. chagasi in BALB/c [ 26 ]; L. braziliensis in hamster [ 29 ]; and now L. amazonensis in C57BL/6 mice, is associated with IFN-gamma production. These results together demonstrate the importance of IFN-gamma as the major marker for vaccine studies against leishmaniasis.…”

“…However, when the same antigen was tested by intranasal route, it induced protection on BALB/c mice [ 21 ]. Mucosal vaccine elicits immune responses effective against several pathogens [ 22 ], and the intranasal route has been effective against leishmaniasis using BALB/c mice [ 23 – 28 ] and hamster [ 29 , 30 ] models.…”

Syrian Hamsters as a Small Animal Model for Emerging Infectious Diseases: Advances in Immunologic Methods

“…For the development of vaccines and therapeutic approaches, some consider hamsters a higher standard as small animal model than mice and as such hamsters have been utilized in a wide range of models, from those examining diabetes, atherosclerosis, neural plasticity, to cancer (Table 1) (Bhathena et al 2011;Dillard et al 2010;Jové et al 2013;Staffend and Meisel 2012;Woods et al 2015;Vijayalingam et al 2014). However, the use of hamsters for models of pathogenic human diseases may be the most valuable due to comparable disease progression seen in hamsters to that of humans for many infectious diseases including bacteria, viruses, and parasites (Dondji et al 2008; da Silva-Couto et al 2015;Kuehne et al 2014;Safronetz et al 2012). Specifically, hamsters are used as a disease model for many high consequence pathogens such as bunyaviruses, arenaviruses, henipaviruses, flaviviruses, alphaviruses, filoviruses, and SARS-corona virus (Table 1) (Safronetz et al 2009Brown et al 2011;Schountz et al 2015;DeBuysscher et al 2013;Gowen and Holbrook 2008;Steele and Twenhafel 2010;Ebihara et al 2012;Gowen et al 2010;Roberts et al 2010).…”

“…The use of hamsters as an animal model has increased greatly in recent years due to their ability to recapitulate human disease in models for diseases like Hantavirus, Ebola virus, Nipah virus, C difficile, Leishmania spp., as well as cancers, and atherosclerosis (Dillard et al 2010;Jové et al 2013;Woods et al 2015;da Silva-Couto et al 2015;Kuehne et al 2014;Safronetz et al 2009Safronetz et al , 2012DeBuysscher et al 2013;Ebihara et al 2012). The realization of hamsters as valuable animal models has led to their use in studying disease course for many pathogens.…”