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Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis.

Shahbazi M, Zahedifard F, Taheri T, Taslimi Y, Jamshidi S, Shirian S, Mahdavi N, Hassankhani M, Daneshbod Y, Zarkesh-Esfahani SH, Papadopoulou B, Rafati S - PLoS ONE (2015)

Bottom Line: It is a severe chronic disease with generalized parasite spread to the reticuloendothelial system, such as spleen, liver and bone marrow and is often fatal when left untreated.In the past decade, various subunits and DNA antigens have been identified as potential vaccine candidates in experimental animal models, but none has been approved for human use so far.We showed that vaccinated animals produced significantly higher levels of IgG2, but not IgG1, and also IFN-γ and TNF-α, but low IL-10 levels, before and after challenge as compared to control animals.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, 69 Pasteur Ave., Tehran, 13164, Iran; Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

ABSTRACT
Canine Visceral Leishmaniasis (CVL) is a major veterinary and public health problem caused by Leishmania infantum (L. infantum) in many endemic countries. It is a severe chronic disease with generalized parasite spread to the reticuloendothelial system, such as spleen, liver and bone marrow and is often fatal when left untreated. Control of VL in dogs would dramatically decrease infection pressure of L. infantum for humans, since dogs are the main domestic reservoir. In the past decade, various subunits and DNA antigens have been identified as potential vaccine candidates in experimental animal models, but none has been approved for human use so far. In this study, we vaccinated outbreed dogs with a prime-boost regimen based on recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinase genes (CPA and CPB without its unusual C-terminal extension (CPB-CTE) and evaluated its immunogenicity and protective immunity against L. infantum infectious challenge. We showed that vaccinated animals produced significantly higher levels of IgG2, but not IgG1, and also IFN-γ and TNF-α, but low IL-10 levels, before and after challenge as compared to control animals. Protection in dogs was also correlated with a strong DTH response and low parasite burden in the vaccinated group. Altogether, immunization with recombinant L. tarentolae A2-CPA-CPB-CTE was proven to be immunogenic and induced partial protection in dogs, hence representing a promising live vaccine candidate against CVL.

No MeSH data available.


Related in: MedlinePlus

Immunocytochemical (ICC) staining of bone marrow with different infection grades (grades I, II, III and severe infection as grade IV) in dogs of different groups.Panels A and B show infection with grade I and II belonging to G1; panels C and D infection with grades II and III belonging to G2; panels E and F, infection with grades III and IV belonging to G3. Intracytoplasmic leishman bodies (arrow headed), free leishman bodies (arrows), magnification X200.
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pone.0132794.g005: Immunocytochemical (ICC) staining of bone marrow with different infection grades (grades I, II, III and severe infection as grade IV) in dogs of different groups.Panels A and B show infection with grade I and II belonging to G1; panels C and D infection with grades II and III belonging to G2; panels E and F, infection with grades III and IV belonging to G3. Intracytoplasmic leishman bodies (arrow headed), free leishman bodies (arrows), magnification X200.

Mentions: Quantified amastigote density in Fine Needle Aspiration (FNA) and ICC smears for Leishmania were classified by two independent observers. The density of amastigotes in the G1 (vaccinated group) was grade I and II. Respectively, three and six cases of G1 showed grade I and grade II cytologically as well as immunocytochemically (Table 1). The density of amastigotes in the G2 and G3 was varying from grade I to IV. Two cases of both G2 and G3 groups had grade I, also four cases of G2 and two cases of G3 was verified as grade II. One case of G2 and two cases of G3 showed grade III. Severe parasite loading (grade IV) was seen in one case of G2 and three cases of G3. Cytologically and immunocytochemically, the density of amastigotes in G1 was lower than in G2 and G3 as shown in Table 1 and Fig 5. Cytologically, there was no dog with grade III and IV in group G1 as compared to G2 and G3 (2 dogs in G2 and 5 dogs in G3 with grade III and IV). Our observations indicate that group G3 had the highest number of dogs with grade III and IV (p<0.05).


Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis.

Shahbazi M, Zahedifard F, Taheri T, Taslimi Y, Jamshidi S, Shirian S, Mahdavi N, Hassankhani M, Daneshbod Y, Zarkesh-Esfahani SH, Papadopoulou B, Rafati S - PLoS ONE (2015)

Immunocytochemical (ICC) staining of bone marrow with different infection grades (grades I, II, III and severe infection as grade IV) in dogs of different groups.Panels A and B show infection with grade I and II belonging to G1; panels C and D infection with grades II and III belonging to G2; panels E and F, infection with grades III and IV belonging to G3. Intracytoplasmic leishman bodies (arrow headed), free leishman bodies (arrows), magnification X200.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4509652&req=5

pone.0132794.g005: Immunocytochemical (ICC) staining of bone marrow with different infection grades (grades I, II, III and severe infection as grade IV) in dogs of different groups.Panels A and B show infection with grade I and II belonging to G1; panels C and D infection with grades II and III belonging to G2; panels E and F, infection with grades III and IV belonging to G3. Intracytoplasmic leishman bodies (arrow headed), free leishman bodies (arrows), magnification X200.
Mentions: Quantified amastigote density in Fine Needle Aspiration (FNA) and ICC smears for Leishmania were classified by two independent observers. The density of amastigotes in the G1 (vaccinated group) was grade I and II. Respectively, three and six cases of G1 showed grade I and grade II cytologically as well as immunocytochemically (Table 1). The density of amastigotes in the G2 and G3 was varying from grade I to IV. Two cases of both G2 and G3 groups had grade I, also four cases of G2 and two cases of G3 was verified as grade II. One case of G2 and two cases of G3 showed grade III. Severe parasite loading (grade IV) was seen in one case of G2 and three cases of G3. Cytologically and immunocytochemically, the density of amastigotes in G1 was lower than in G2 and G3 as shown in Table 1 and Fig 5. Cytologically, there was no dog with grade III and IV in group G1 as compared to G2 and G3 (2 dogs in G2 and 5 dogs in G3 with grade III and IV). Our observations indicate that group G3 had the highest number of dogs with grade III and IV (p<0.05).

Bottom Line: It is a severe chronic disease with generalized parasite spread to the reticuloendothelial system, such as spleen, liver and bone marrow and is often fatal when left untreated.In the past decade, various subunits and DNA antigens have been identified as potential vaccine candidates in experimental animal models, but none has been approved for human use so far.We showed that vaccinated animals produced significantly higher levels of IgG2, but not IgG1, and also IFN-γ and TNF-α, but low IL-10 levels, before and after challenge as compared to control animals.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, 69 Pasteur Ave., Tehran, 13164, Iran; Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

ABSTRACT
Canine Visceral Leishmaniasis (CVL) is a major veterinary and public health problem caused by Leishmania infantum (L. infantum) in many endemic countries. It is a severe chronic disease with generalized parasite spread to the reticuloendothelial system, such as spleen, liver and bone marrow and is often fatal when left untreated. Control of VL in dogs would dramatically decrease infection pressure of L. infantum for humans, since dogs are the main domestic reservoir. In the past decade, various subunits and DNA antigens have been identified as potential vaccine candidates in experimental animal models, but none has been approved for human use so far. In this study, we vaccinated outbreed dogs with a prime-boost regimen based on recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinase genes (CPA and CPB without its unusual C-terminal extension (CPB-CTE) and evaluated its immunogenicity and protective immunity against L. infantum infectious challenge. We showed that vaccinated animals produced significantly higher levels of IgG2, but not IgG1, and also IFN-γ and TNF-α, but low IL-10 levels, before and after challenge as compared to control animals. Protection in dogs was also correlated with a strong DTH response and low parasite burden in the vaccinated group. Altogether, immunization with recombinant L. tarentolae A2-CPA-CPB-CTE was proven to be immunogenic and induced partial protection in dogs, hence representing a promising live vaccine candidate against CVL.

No MeSH data available.


Related in: MedlinePlus