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Microbial Immunity and Vaccines

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

Maija Toropainen, Anna Raitolehto, Isabelle Henckaerts, Dominique Wauters, Jan Poolman, Pascal Lestrate, Helena Käyhty
Maija Toropainen
1National Public Health Institute (KTL), Department of Vaccines, Helsinki, Finland
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  • For correspondence: maija.toropainen@ktl.fi
Anna Raitolehto
1National Public Health Institute (KTL), Department of Vaccines, Helsinki, Finland
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Isabelle Henckaerts
2GlaxoSmithKline Biologicals, Rixensart, Belgium
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Dominique Wauters
2GlaxoSmithKline Biologicals, Rixensart, Belgium
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Jan Poolman
2GlaxoSmithKline Biologicals, Rixensart, Belgium
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Pascal Lestrate
2GlaxoSmithKline Biologicals, Rixensart, Belgium
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Helena Käyhty
1National Public Health Institute (KTL), Department of Vaccines, Helsinki, Finland
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DOI: 10.1128/IAI.00418-08
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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 (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.

  • Copyright © 2008 American Society for Microbiology
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Pneumococcal Haemophilus influenzae Protein D Conjugate Vaccine Induces Antibodies That Inhibit Glycerophosphodiester Phosphodiesterase Activity of Protein D
Maija Toropainen, Anna Raitolehto, Isabelle Henckaerts, Dominique Wauters, Jan Poolman, Pascal Lestrate, Helena Käyhty
Infection and Immunity Sep 2008, 76 (10) 4546-4553; DOI: 10.1128/IAI.00418-08

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Pneumococcal Haemophilus influenzae Protein D Conjugate Vaccine Induces Antibodies That Inhibit Glycerophosphodiester Phosphodiesterase Activity of Protein D
Maija Toropainen, Anna Raitolehto, Isabelle Henckaerts, Dominique Wauters, Jan Poolman, Pascal Lestrate, Helena Käyhty
Infection and Immunity Sep 2008, 76 (10) 4546-4553; DOI: 10.1128/IAI.00418-08
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KEYWORDS

Antibodies, Bacterial
Bacterial Proteins
Carrier Proteins
lipoproteins
Phosphoric Diester Hydrolases
Pneumococcal Vaccines

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