RESUMEN
A new approach to the development of a vaccine against meningococci of serogroups A and B was proposed. It involves the synthesis of conjugates of high-molecular capsule polysaccharides of the serogroup A meningococcus (PsA) with earlier synthesized protective fragments of membrane proteins from serogroup B meningococci. The conjugates were synthesized using a method that consists of the generation of aldehyde groups by oxidizing free vicinal hydroxyl groups of PsA and subsequent reaction of these groups with amino groups of the peptide. The reaction proceeds with the intermediate formation of the Schiff base, which is reduced to the stable secondary amine. The main parameters of the reaction were optimized in the synthesis of a PsA conjugate with a model peptide and methods of their characterization were developed. The reproducibility and efficiency of the synthetic procedure were demonstrated by the example of synthesis of PsA conjugates with fragments of protein PorA from the outer membrane of the serogroup B meningococcus. It was shown that, when administered without adjuvant, a conjugate of PsA with a protective peptide, which represents an exposed conserved fragment 306-332 of protein PorA, stimulates the formation of antibodies to the peptide and polysaccharide moieties of the molecule and is also capable of decreasing the degree of bacteremia in animals infected with serogroup A and serogroup B meningococci. The approach can be applied to the development of a complex vaccine for serogroup A and serogroup B meningococci.
Asunto(s)
Antígenos Bacterianos/inmunología , Proteínas de la Membrana Bacteriana Externa/química , Vacunas Meningococicas/síntesis química , Neisseria meningitidis Serogrupo A/inmunología , Neisseria meningitidis Serogrupo B/inmunología , Fragmentos de Péptidos/química , Polisacáridos Bacterianos/química , Secuencia de Aminoácidos , Animales , Bacteriemia/inmunología , Bacteriemia/microbiología , Bacteriemia/prevención & control , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Meningococicas/inmunología , Ratones , Datos de Secuencia Molecular , Vacunas Sintéticas/química , Vacunas Sintéticas/inmunologíaRESUMEN
Immunization of mice with synthetic peptide fragments of conservative sites of meningococcal outer membrane proteins led to defense formation against infection with virulent serogroup A and B Meningococci. The role of cellular immunity in the formation of defense against meningococcal infection after immunization with the peptides and the possibility of stimulating lymphocyte population with these peptides were demonstrated.
Asunto(s)
Proteínas de la Membrana Bacteriana Externa/inmunología , Infecciones Meningocócicas/prevención & control , Fragmentos de Péptidos/inmunología , Animales , Transfusión de Linfocitos , Ratones , Linfocitos T/fisiología , Linfocitos T/trasplante , Factores de TiempoRESUMEN
Peptide fragments of conservative sites of PorA, OpaB, and NspA proteins of the outer membrane of serogroup B meningococci were synthesized. These peptides caused a pronounced protective effect in immunized mice infected with virulent homologous and heterologous strains of serogroups B and A meningococci. The protective effect appreciably increased, if the studied peptides were associated in a polycomponent preparation, which can be used in the construction of meningococcal bivalent B+A vaccine.