title: Pre-clinical evaluation of a 15-valent pneumococcal conjugate vaccine (PCV15-CRM197) in an infant-rhesus monkey immunogenicity model.
abstract: The incidence of invasive pneumococcal disease (IPD), caused by the approximately 91 serotypes of Streptococcus pneumoniae (PN), varies geographically and temporally as a result of changing epidemiology and vaccination patterns as well as due to regional measurement differences. 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 and elsewhere, 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. In response, 10- and 13-valent PCVs have recently been licensed. To further increase serotype 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. Vaccine immunogenicity was evaluated in infant rhesus monkeys since they, like human infants, respond poorly to unconjugated PN PS. Infant (2-3 month old) rhesus monkeys were vaccinated three 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 additional serotypes.
authors.affiliation: Department of Vaccines Research, Merck & Co., Inc., West Point, PA 19486, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Skinner
authors.forename: Lani
authors.initials: L
authors.lastname: Indrawati
authors.forename: Jayme
authors.initials: J
authors.lastname: Cannon
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Blue
authors.forename: Michael
authors.initials: M
authors.lastname: Winters
authors.forename: John
authors.initials: J
authors.lastname: Macnair
authors.forename: Narahari
authors.initials: N
authors.lastname: Pujar
authors.forename: Walter
authors.initials: W
authors.lastname: Manger
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zhang
authors.forename: Joseph
authors.initials: J
authors.lastname: Antonello
authors.forename: John
authors.initials: J
authors.lastname: Shiver
authors.forename: Michael
authors.initials: M
authors.lastname: Caulfield
authors.forename: Jon H
authors.initials: JH
authors.lastname: Heinrichs
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D007074:Immunoglobulin G / Q000097:blood; D008253:Macaca mulatta; D011008:Pneumococcal Infections / Q000276:immunology* / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D012703:Serotyping; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate