title: Development and phase 1 clinical testing of a conjugate vaccine against meningococcus A and C.
abstract: A conjugate vaccine against meningococcus A and C was prepared using the non-toxic mutant of diphtheria toxin CRM 197 as a carrier protein. Capsular polysaccharides of Neisseria meningitidis group A and C were hydrolysed and the resulting oligosaccharides were then coupled to CRM 197 in order to obtain conjugates with a carbohydrate content of 25-30%. The final vaccine that contained 11 micrograms of each oligosaccharide and 88 micrograms of CRM 197 was used to immunize mice and rabbits. After the preclinical studies which showed that the vaccine was safe and immunogenic in animal models, a pilot phase 1 clinical trial, blind versus placebo, was performed on adult volunteers. The difference between the incidence of adverse reactions associated with vaccine and placebo administration was not statistically significant. All the volunteers who received the vaccine had a significant increase in antibodies to group A and C meningococcal capsular polysaccharides after the first dose.
authors.affiliation: Sclavo R & D Vaccines, Siena, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Costantino
authors.forename: S
authors.initials: S
authors.lastname: Viti
authors.forename: A
authors.initials: A
authors.lastname: Podda
authors.forename: M A
authors.initials: MA
authors.lastname: Velmonte
authors.forename: L
authors.initials: L
authors.lastname: Nencioni
authors.forename: R
authors.initials: R
authors.lastname: Rappuoli
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood; D001426:Bacterial Proteins / Q000302:isolation & purification; D002240:Carbohydrate Sequence; D004167:Diphtheria Toxin / Q000302:isolation & purification; D004311:Double-Blind Method; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D006001:Glycoconjugates / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007114:Immunization; D051379:Mice; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000276:immunology*; D009844:Oligosaccharides / Q000737:chemistry; D010865:Pilot Projects; D011446:Prospective Studies; D011817:Rabbits; D014765:Viral Vaccines / Q000009:adverse effects / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D001426:Bacterial Proteins; D004167:Diphtheria Toxin; D006001:Glycoconjugates; D009844:Oligosaccharides; D014765:Viral Vaccines; C028581:CRM197 (non-toxic variant of diphtheria toxin)