Pneumococcal Haemophilus influenzae Protein D Conjugate Vaccine Induces Antibodies That Inhibit Glycerophosphodiester Phosphodiesterase Activity of Protein D

• Published in: Infection and Immunity Vol. 76; no. 10; pp. 4546 - 4553
• Main Authors: Toropainen, Maija, Raitolehto, Anna, Henckaerts, Isabelle, Wauters, Dominique, Poolman, Jan, Lestrate, Pascal, Käyhty, Helena
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.10.2008; American Society for Microbiology (ASM)
• Subjects: Age Factors; Antibodies, Bacterial - blood; Antibodies, Bacterial - immunology; Applied microbiology; Bacterial Proteins - antagonists & inhibitors; Bacteriology; Biological and medical sciences; Carrier Proteins - antagonists & inhibitors; Fundamental and applied biological sciences. Psychology; Haemophilus influenzae; Humans; Immunoglobulin D; Immunoglobulin G - blood; Immunoglobulin G - immunology; Infant; Lipoproteins - antagonists & inhibitors; Microbial Immunity and Vaccines; Microbiology; Miscellaneous; Neutralization Tests; Phosphoric Diester Hydrolases - metabolism; Pneumococcal Vaccines - immunology; Streptococcus pneumoniae; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Conjugate; Microbiology; Enzyme; Antibody; Esterases; Vaccine; Phosphoric diester hydrolases; Glycerophosphodiester phosphodiesterase; Immunity; Haemophilus influenzae; Protein; Streptococcus pneumoniae; Pasteurellaceae; Streptococcaceae; Bacteria; Hydrolases; Micrococcales
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00418-08

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 (rs, ~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.