RESUMO
P64k is a meningococcal protein from Neisseria meningitidis that has been obtained by recombinant DNA technology. Recombinant P64k has been extensively characterized by physicochemical and immunological methods. Lately this protein has been found to act as a versatile immunological carrier for weak antigens in mice. In the present work, a Phase I clinical trial was carried out in healthy volunteers who received three inoculations of either placebo or recombinant P64k (20 or 50 microg). No severe adverse events occurred during the trial. Only mild adverse events in ten volunteers were observed. At 1 month after the third dose, 15 out of 18 volunteers (83.3%) who received the recombinant antigen had a P64k-specific antibody titre > or =1:100, as detected by ELISA. A fourth dose, given 9 months after the third one, elicited a potent booster immune response in P64k vaccinees. Accordingly, these P64k formulations were considered safe and immunogenic in healthy human volunteers.
Assuntos
Antígenos de Bactérias/efeitos adversos , Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/efeitos adversos , Proteínas da Membrana Bacteriana Externa/imunologia , Neisseria meningitidis/imunologia , Adulto , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/administração & dosagem , Proteínas da Membrana Bacteriana Externa/administração & dosagem , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Esquemas de Imunização , Masculino , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/imunologiaRESUMO
To increase the humoral immune response against two cyclic synthetic peptides, derived from variable regions within the outer membrane meningococcal protein PorA (subtypes 19 and 15), we conjugated the peptides to P64k, a novel carrier protein from the same bacterium expressed in Escherichia coli. In addition, one of these peptides was restricted to a linear conformation before it was chemically coupled to the carrier. The conjugates were administered to mice in a three-dose immunization schedule, resulting in a potent anti-peptide immune response, which suggested that chemical conjugation to this carrier provided T-cell help. Antisera directed to the three conjugates reacted with Neisseria meningitidis outer membrane PorA upon immunoblot analysis. Moreover, in two out of three conjugates, the anti-peptide sera reacted with native meningococcal outer membrane vesicles in ELISA.
