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Infection and Immunity, October 2008, p. 4546-4553, Vol. 76, No. 10
0019-9567/08/$08.00+0     doi:10.1128/IAI.00418-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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

Maija Toropainen,1* Anna Raitolehto,1 Isabelle Henckaerts,2 Dominique Wauters,2 Jan Poolman,2 Pascal Lestrate,2 and Helena Käyhty1

National Public Health Institute (KTL), Department of Vaccines, Helsinki, Finland,1 GlaxoSmithKline Biologicals, Rixensart, Belgium2

Received 4 April 2008/ Returned for modification 24 May 2008/ Accepted 11 July 2008

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.

* Corresponding author. Mailing address: National Public Health Institute, Department of Vaccines, Vaccine Immunology Laboratory, Mannerheimintie 166, FIN-00300 Helsinki, Finland. Phone: 358-9-47448873. Fax: 358-9-47448599. E-mail: maija.toropainen{at}ktl.fi

{triangledown} Published ahead of print on 21 July 2008.

Editor: A. Camilli

Infection and Immunity, October 2008, p. 4546-4553, Vol. 76, No. 10
0019-9567/08/$08.00+0     doi:10.1128/IAI.00418-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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