DNA Vaccine Encoding the Chimeric Form of Schistosoma mansoni Sm-TSP2 and Sm29 Confers Partial Protection against Challenge Infection.
Schistosomiasis is an important parasitic disease worldwide that affects more than 207 million people in 76 countries and causes approximately 250,000 deaths per year. The best long-term strategy to control schistosomiasis is through immunization combined with drug treatment. Due to the ability of DNA vaccines to generate humoral and cellular immune responses, such vaccines are considered a promising approach against schistosomiasis. Sm29 and tetraspanin-2 (Sm-TSP2) are two proteins that are located in the S. mansoni tegument of adult worms and schistosomula and induce high levels of protection through recombinant protein immunization. In this study, we transfected BHK-21 cells with plasmids encoding Sm29, Sm-TSP2 or a chimera containing both genes. Using RT-PCR analysis and western blot, we confirmed that the DNA vaccine constructs were transcribed and translated, respectively, in BHK-21 cells. After immunization of mice, we evaluated the reduction in worm burden. We observed worm burden reductions of 17-22%, 22%, 31-32% and 24-32% in animals immunized with the pUMVC3/Sm29, pUMVC3/SmTSP-2, pUMVC3/Chimera and pUMVC3/Sm29 + pUMVC3/SmTSP-2 plasmids, respectively. We evaluated the humoral response elicited by DNA vaccines, and animals immunized with pUMVC3/Sm29 and pUMVC3/Sm29 + pUMVC3/SmTSP-2 showed higher titers of anti-Sm29 antibodies. The cytokine profile produced by the spleen cells of immunized mice was then evaluated. We observed higher production of Th1 cytokines, such as TNF-α and IFN-γ, in vaccinated mice and no significant production of IL-4 and IL-5. The DNA vaccines tested in this study showed the ability to generate a protective immune response against schistosomiasis, probably through the production of Th1 cytokines. However, future strategies aiming to optimize the protective response induced by a chimeric DNA construct need to be developed.
Departamento de Bioquímica e Imunologia do Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), CNPq MCT, 31270-901, Belo Horizonte, MG, Brazil.
Natan Raimundo
NR
Gonçalves de Assis
Departamento de Bioquímica e Imunologia do Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), CNPq MCT, 31270-901, Belo Horizonte, MG, Brazil.
Suellen
S
Batistoni de Morais
Departamento de Bioquímica e Imunologia do Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), CNPq MCT, 31270-901, Belo Horizonte, MG, Brazil.
Bárbara Castro Pimentel
BC
Figueiredo
Departamento de Bioquímica e Imunologia do Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), CNPq MCT, 31270-901, Belo Horizonte, MG, Brazil.
Natasha Delaqua
ND
Ricci
Departamento de Bioquímica e Imunologia do Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
Leonardo Augusto
LA
de Almeida
Departamento de Biointeração do Instituto de Ciências da Saúde, Universidade Federal da Bahia, 40110-100, Salvador, BA, Brazil.
Carina
C
da Silva Pinheiro
Faculdade de Ceilândia, Universidade de Brasília, 70910-900, Brasília, DF, Brazil.
Vicente de Paulo
Vde P
Martins
Departamento de Bioquímica e Imunologia do Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), CNPq MCT, 31270-901, Belo Horizonte, MG, Brazil.
Sergio Costa
SC
Oliveira
D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology; D000947:Antigens, Helminth / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D006099:Granuloma / Q000469:parasitology / Q000473:pathology; D015801:Helminth Proteins / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D012333:RNA, Messenger; D011994:Recombinant Proteins / Q000276:immunology; D012550:Schistosoma mansoni / Q000235:genetics / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000517:prevention & control*; D013154:Spleen / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D016207:Cytokines; D015801:Helminth Proteins; D007074:Immunoglobulin G; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019444:Vaccines, DNA