Characterization of multivalent pneumococcal conjugate vaccines.

A new heptavalent pneumococcal conjugate vaccine, designed to protect against disease due to serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F, was formulated with aluminium phosphate adjuvant and analysed before testing in infants. Analyses were complicated by the presence of the adjuvant, and by the low level of each antigen; for example, all serotypes were formulated at 2 microg of saccharide /dose (except 6B which was formulated at 4 microg). Type specific analyses were performed on the formulated vaccine, and included determination of immunogenicity and antigenicity; the former was measured by ELISA following immunization of rabbits, the latter was measured by rate nephelometry. Non serotype specific information was also collected, and included total and adsorbed saccharide (by Anthrone assay), and total and adsorbed protein (by Lowry assay). These preclinical data supported the use of the vaccine in infants in a large randomized double-blinded clinical trial in a multiethnic population. The results of this trial show that the vaccine is safe and efficacious. Collectively, the data will be used to support licensure of the heptavalent vaccine, and documents successful scale-up of the formulation process to manufacturing level.