Asunto(s)
Enfermedades Autoinmunes/prevención & control , Control de Enfermedades Transmisibles/métodos , Hipersensibilidad/prevención & control , Inmunoterapia/métodos , Neoplasias/prevención & control , Investigación Biomédica Traslacional/tendencias , Animales , Anticuerpos Monoclonales/biosíntesis , Anticuerpos Monoclonales/uso terapéutico , Antígenos/química , Antígenos/genética , Antígenos/inmunología , Enfermedades Autoinmunes/inmunología , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/biosíntesis , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/biosíntesis , Enfermedades Transmisibles/inmunología , Enfermedades Transmisibles/patología , Citocinas/agonistas , Citocinas/antagonistas & inhibidores , Citocinas/genética , Citocinas/inmunología , Vacunas Fúngicas/administración & dosificación , Vacunas Fúngicas/biosíntesis , Humanos , Hipersensibilidad/inmunología , Inmunoensayo/métodos , Neoplasias/inmunología , Vacunas Virales/administración & dosificación , Vacunas Virales/biosíntesisRESUMEN
Pneumocystis spp. are opportunistic fungal pathogens that are closely associated with severe pneumonia and pulmonary complications in patients with impaired immunity. In this study, the antigenic epitopes of the gene encoding the 55 kDa antigen fragment of Pneumocystis (p55), which may play an important role in Pneumocystis pneumonia, were analyzed. A gene containing tandem variants of the p55 antigen was synthesized and named the tandem antigen gene (TAG). TAG's potential as a DNA vaccine was assessed in immunosuppressed rats. Immunization with p55-TAG DNA vaccine significantly reduced both the pathogen burden and lung-weight to body-weight ratios. Additionally, p55-TAG vaccination in immunosuppressed rats elicited both cell-mediated and humoral immunity.
Asunto(s)
Antígenos Fúngicos/genética , Antígenos Fúngicos/inmunología , Proteínas Fúngicas/genética , Proteínas Fúngicas/inmunología , Vacunas Fúngicas/inmunología , Pneumocystis carinii/inmunología , Neumonía por Pneumocystis/prevención & control , Vacunas de ADN/inmunología , Animales , Anticuerpos Antifúngicos/sangre , Anticuerpos Antifúngicos/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/sangre , Epítopos de Linfocito B/inmunología , Femenino , Vacunas Fúngicas/biosíntesis , Vacunas Fúngicas/genética , Vacunas Fúngicas/farmacología , Células HEK293 , Humanos , Inmunidad Celular/inmunología , Inmunoglobulina G/sangre , Enfermedades Pulmonares Fúngicas/patología , Enfermedades Pulmonares Fúngicas/prevención & control , Pneumocystis carinii/genética , Neumonía por Pneumocystis/inmunología , Neumonía por Pneumocystis/microbiología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/inmunología , Linfocitos T/inmunología , Vacunas de ADN/biosíntesis , Vacunas de ADN/genética , Vacunas de ADN/farmacologíaRESUMEN
We synthesized Cryptococcus neoformans serotype A glucuronoxylomannan (GXM) conjugate vaccines under conditions suitable for human use to prevent disseminated cryptococcosis. The purified, sonicated GXM was derivatized with adipic acid dihydrazide through either hydroxyl or carboxyl groups and then covalently bound to tetanus toxoid (TT) or Pseudomonas aeruginosa exoprotein A (rEPA). The immunogenicity of these conjugates was evaluated in BALB/c and general purpose mice by subcutaneous injection in saline. The conjugates elicited higher GXM antibody responses than GXM alone. Booster immunoglobulin G (IgG) and IgM responses were elicited by all conjugates in BALB/c mice. The conjugates prepared through hydroxyl activation (GXM-TT2 and GXM-rEPA) were more immunogenic than the one prepared through carboxyl activation (GXM-TT1). GXM antibody response was enhanced by the administration of monophosphoryl lipid A 2 days following the injection of GXM-TT2 (P less than 0.03). The conjugates also elicited IgG antibodies to the carrier proteins. Gel diffusion tests using conjugate-induced hyperimmune sera and chemically modified GXMs suggested that the specificity of GXM-TT1-induced antibodies was conferred by the O-acetyl groups. Hyperimmune sera generated by GXM-TT2 precipitated with the chemically unmodified and the de-O-acetylated GXMs but not with the carboxyl-reduced and de-O-acetylated GXM. GXM-TT2-induced hyperimmune serum also precipitated with the capsular polysaccharides of C. neoformans serotypes D, B, and C. The conjugate vaccines prepared through hydroxyl activation of the GXM are sufficiently immunogenic and appear to be suitable for clinical evaluation.