Production and control of a Brazilian tailor-made meningococcal B vaccineShort title: Brazilian meningococcal B vaccine production

Abstract

Meningococcal disease has been a public health problem in Brazil since the serogroups A and C epidemics occurred in the 1970s. The Oswaldo Cruz Foundation in Brazil has been working to develop a serogroup B meningococcal vaccine composed of detergent-treated outer membrane vesicles (OMV) and detoxified endotoxin (dLOS) from Neisseria meningitidis serogroup B prevalent strains. Experimental vaccine were produced in a pilot-scale under Good Manufacturing Practice condition (GMP). Physicochemical and biological controls were established based on what has been reported previously for OMV vaccines. The developed vaccine contained the main class 1, 2, 3, and 5 proteins, some minor iron-regulated proteins, and 5-10% residual lipopolysaccharide related to total protein content. The dLOS was added, as a vaccine component, in half of the total protein amount. The pyrogenicity of the final products, based on the residual LOS in OMVs, varied from 1.01 to 2.24 ng LOS/kg rabbit. Three experimental vaccines, were highly immunogenic in mice with better performance using higher antigen concentrations.