title: Pneumococcal Haemophilus influenzae protein D conjugate vaccine induces antibodies that inhibit glycerophosphodiester phosphodiesterase activity of protein D.
abstract: Haemophilus influenzae outer membrane protein D (PD) is a glycerophosphodiester phosphodiesterase (GlpQ) activity-possessing virulence factor and a promising vaccine antigen, providing 35.3% efficacy against acute otitis media caused by nontypeable H. influenzae (NTHI) when it was used as a carrier protein in a novel pneumococcal PD conjugate (Pnc-PD) vaccine. To study if PD-induced protection against NTHI could be due to antibodies that inhibit or neutralize its enzymatic activity, a GlpQ enzyme inhibition assay was developed, and serum samples collected from Finnish infants before and after Pnc-PD vaccination were analyzed for enzyme inhibition and anti-PD immunoglobulin G (IgG) antibody concentration. Before vaccination at age 2 months, the majority (84%) of infants (n = 69) had no detectable anti-PD IgG antibodies, and all were enzyme inhibition assay negative (inhibition index, <20). At age 13 to 16 months, all infants receiving three or four doses of Pnc-PD had detectable anti-PD IgG antibodies and 36% (8/22 infants) of the infants receiving three doses and 26% (6/23 infants) of the infants receiving four doses of Pnc-PD were inhibition assay positive (inhibition index, >/=20). No significant rise in anti-PD IgG antibodies or enzyme inhibition among control vaccinees (n = 24) receiving three doses of hepatitis B vaccine was detected. A modest correlation (r(s), approximately 0.66) between anti-PD IgG concentration and enzyme inhibition was detected; however, their kinetics were clearly different. These data suggest that measurement of antibody responses that inhibit PD's enzymatic activity could be a useful tool for assessing Pnc-PD vaccine-induced protective immunity against NTHI.
authors.affiliation: Department of Vaccines, Vaccine Immunology Laboratory, National Public Health Institute, KTL, Helsinki, Finland. maija.toropainen@ktl.fi
authors.forename: Maija
authors.initials: M
authors.lastname: Toropainen
authors.forename: Anna
authors.initials: A
authors.lastname: Raitolehto
authors.forename: Isabelle
authors.initials: I
authors.lastname: Henckaerts
authors.forename: Dominique
authors.initials: D
authors.lastname: Wauters
authors.forename: Jan
authors.initials: J
authors.lastname: Poolman
authors.forename: Pascal
authors.initials: P
authors.lastname: Lestrate
authors.forename: Helena
authors.initials: H
authors.lastname: Käyhty
mesh_terms: D000367:Age Factors; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007072:Immunoglobulin D; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007223:Infant; D008074:Lipoproteins / Q000037:antagonists & inhibitors*; D009500:Neutralization Tests; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D022242:Pneumococcal Vaccines / Q000276:immunology*; D018074:Vaccines, Conjugate
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D008074:Lipoproteins; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate; D010727:Phosphoric Diester Hydrolases; C067989:glpQ protein, Haemophilus influenzae; C038133:glycerophosphodiester phosphodiesterase