RESUMO
The meta 1 gene of Leishmania is conserved across the genus and encodes a protein upregulated in metacyclic promastigotes. Meta 1 constitutive overexpressing mutants show increased virulence to mice. In this paper, both meta 1 recombinant protein and plasmids bearing the meta 1 gene were tested for their antigenicity and potential for inducing protective immunity in mice. Vaccination with the recombinant protein induced a predominant Th2-type of response and did not result in protection upon challenge with live parasites. Surprisingly, the expected reversal to a CD4(+) Th1-type of response upon genetic immunisation by the intramuscular route was not observed. Instead, vaccination with either the meta 1 gene alone or in fusion with the monocyte chemotactic protein (MCP)-3 cDNA induced a Th2-type of response that correlated with lack of protection against infection.
Assuntos
Anticorpos Antiprotozoários/biossíntese , Leishmania major/imunologia , Proteínas de Protozoários/administração & dosagem , Vacinas Protozoárias/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/imunologia , Vacinas de DNA/administração & dosagem , Animais , Células COS/química , Células COS/metabolismo , Linhagem Celular , Quimiocina CCL7 , Chlorocebus aethiops , Citocinas/biossíntese , Feminino , Leishmania mexicana/imunologia , Leishmaniose Cutânea/prevenção & controle , Leishmaniose Tegumentar Difusa/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Quimioatraentes de Monócitos/biossíntese , Proteínas Quimioatraentes de Monócitos/genética , Proteínas Quimioatraentes de Monócitos/imunologia , Proteínas Quimioatraentes de Monócitos/uso terapêutico , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Vacinas Protozoárias/imunologia , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Solubilidade , Subpopulações de Linfócitos T/imunologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Vacinas de DNA/imunologia , Vacinas de DNA/uso terapêutico , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologiaRESUMO
The meta 1 gene of Leishmania is conserved across the genus and encodes a protein upregulated in metacyclic promastigotes. Meta 1 constitutive overexpressing mutants show increased virulence to mice. In this paper, both meta 1 recombinant protein and plasmids bearing the meta 1 gene were tested for their antigenicity and potential for inducing protective immunity in mice. Vaccination with the recombinant protein induced a predominant Th2-type of response and did not result in protection upon challenge with live parasites. Surprisingly, the expected reversal to a CD4+ Th1-type of response upon genetic immunisation by the intramuscular route was not observed. Instead, vaccination with either the meta 1 gene alone or in fusion with the monocyte chemotactic protein (MCP)-3 cDNA induced a Th2-type of response that correlated with lack of protection against infection.
