DEVELOPMENT AND PHASE-1 CLINICAL-TESTING OF A CONJUGATE VACCINE AGAINST MENINGOCOCCUS-A AND MENINGOCOCCUS-C

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-mu-g of each oligosaccharide and 88-mu-g 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.