RESUMEN
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.
Asunto(s)
Anticuerpos Antiprotozoarios/biosíntesis , Leishmania major/inmunología , Proteínas Protozoarias/administración & dosificación , Vacunas Antiprotozoos/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/inmunología , Vacunas de ADN/administración & dosificación , Animales , Células COS/química , Células COS/metabolismo , Línea Celular , Quimiocina CCL7 , Chlorocebus aethiops , Citocinas/biosíntesis , Femenino , Leishmania mexicana/inmunología , Leishmaniasis Cutánea/prevención & control , Leishmaniasis Cutánea Difusa/prevención & control , Ratones , Ratones Endogámicos BALB C , Proteínas Quimioatrayentes de Monocitos/biosíntesis , Proteínas Quimioatrayentes de Monocitos/genética , Proteínas Quimioatrayentes de Monocitos/inmunología , Proteínas Quimioatrayentes de Monocitos/uso terapéutico , Proteínas Protozoarias/genética , Proteínas Protozoarias/inmunología , Vacunas Antiprotozoos/inmunología , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Solubilidad , Subgrupos de Linfocitos T/inmunología , Células TH1/inmunología , Células TH1/metabolismo , Células Th2/inmunología , Células Th2/metabolismo , Vacunas de ADN/inmunología , Vacunas de ADN/uso terapéutico , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/inmunologíaRESUMEN
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.