title: Effect of individual conjugate dose on immunogenicity of type 6B pneumococcal polysaccharide-N. meningitidis outer membrane protein complex conjugate vaccines in infant rhesus monkeys.
abstract: A pneumococcal conjugate vaccine (PCV) has been developed consisting of capsular polysaccharide (Ps) coupled to the outer membrane protein complex of Neiserria meningitidis serogroup B. Experiments were conducted in infant rhesus monkeys to assess the potential to administer multiple Pn types in a single vaccine. A single type conjugate, 6B, was dosed from 0.025 to 25 microg Ps. Peak anti-6B Ps Ab titers were seen at lower doses of 0.025 and 0.25 microg Ps, while reduced titers of anti-6B Ps Ab were observed at the highest doses of conjugate administered, 2.5 and 25 microg Ps. By mixing free Ps, carrier, or another monovalent PCV with this 6B PCV, it was determined that reduced anti-6B Ps titers at high PCV doses were associated only with the quantity of type-specific Ps in the conjugate. Thus, increasing the amount of carrier protein or adding an additional monovalent conjugate did not significantly affect the response to type 6B Ps. These results suggest that, given an appropriately determined dose per individual pneumococcal Ps type, a multivalent PCV that includes many different types should have satisfactory clinical immunogenicity.
authors.affiliation: Department of Virus and Cell Biology, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: T B
authors.initials: TB
authors.lastname: McNeely
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: T
authors.initials: T
authors.lastname: Bringman
authors.forename: J J
authors.initials: JJ
authors.lastname: Donnelly
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage* / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D008297:Male; D008589:Meningococcal Infections / Q000276:immunology; D022401:Meningococcal Vaccines; D009345:Neisseria meningitidis / Q000276:immunology*; D011008:Pneumococcal Infections / Q000276:immunology; D022242:Pneumococcal Vaccines; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D022401:Meningococcal Vaccines; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate; C105256:five-valent pneumococcal conjugate vaccine