RESUMEN
An artificial antigen forming the C34 trimeric structure targeting membrane-fusion mechanism of HIV-1 has been evaluated as an HIV vaccine. The C34 trimeric molecule was previously designed and synthesized using a novel template with C3-symmetric linkers by us. The antiserum produced by immunization of the C34 trimeric form antigen showed 23-fold higher binding affinity for the C34 trimer than for the C34 monomer and showed significant neutralizing activity. The present results suggest effective strategies of the design of HIV vaccines and anti-HIV agents based on the native structure mimic of proteins targeting dynamic supramolecular mechanisms in HIV fusion.
Asunto(s)
Vacunas contra el SIDA/química , Anticuerpos Anti-VIH/inmunología , Proteína gp41 de Envoltorio del VIH/inmunología , Fragmentos de Péptidos/inmunología , Vacunas contra el SIDA/genética , Secuencia de Aminoácidos , Animales , Fármacos Anti-VIH/química , Línea Celular , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Antígenos VIH/química , Antígenos VIH/inmunología , Proteína gp41 de Envoltorio del VIH/síntesis química , Humanos , Inmunización , Masculino , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Pruebas de Neutralización , Fragmentos de Péptidos/síntesis químicaRESUMEN
A synthetic antigen targeting membrane-fusion mechanism of HIV-1 has a newly designed template with C3-symmetric linkers mimicking N36 trimeric form. The antiserum produced by immunization of the N36 trimeric form antigen showed structural preference in binding to N36 trimer and stronger inhibitory activity against HIV-1 infection than the N36 monomer. Our results suggest an effective strategy of HIV vaccine design based on a relationship to the native structure of proteins involved in HIV fusion mechanisms.