Preclinical evaluation of a 15-valent pneumococcal polysaccharide-protein conjugate vaccine in infant rhesus monkeys (52.20)

Abstract

Abstract The incidence of invasive pneumococcal disease (IPD) caused by the 91 serotypes of Streptococcus pneumoniae (PN) varies geographically and temporally as a result of changing epidemiology and vaccination. Prevnar® (Pfizer), the first licensed pneumococcal conjugate vaccine (PCV), comprises polysaccharides (PS) from 7 serotypes conjugated to the mutant diphtheria toxin carrier protein, CRM197. In the United States, this vaccine has been highly efficacious in reducing the incidence of IPD caused by vaccine serotypes, however, the incidence of non-vaccine serotypes (e.g., 19A, 22F, and 33F) has increased resulting in the need for vaccines with higher valencies. Indeed, 10- and 13-valent PCVs have recently been licensed. For expanded coverage, we have developed a 15-valent PCV containing PS from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F conjugated to CRM197 and formulated on aluminum phosphate adjuvant. The vaccine was tested in infant rhesus monkeys since they, like human infants, do not respond to unconjugated PN PS. Infant (2-3 month old) rhesus monkeys were vaccinated 3 times with PCV-15 or Prevnar® at 2 month intervals, and serotype-specific IgG antibodies were measured using a multiarray electrochemiluminescence (ECL) assay. The results indicate that antibody responses to PCV-15 and Prevnar® were comparable for the 7 common serotypes and that post-vaccination responses to PCV-15 were > 10-fold higher than baseline for the 8 added serotypes.