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Infect. Immun. doi:10.1128/IAI.00418-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

PNEUMOCOCCAL HAEMOPHILUS INFLUENZAE PROTEIN D CONJUGATE VACCINE INDUCE ANTIBODIES THAT INHIBIT GLYCEROPHOSPHODIESTER PHOSPHODIESTERASE ACTIVITY OF PROTEIN D

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

^* To whom correspondence should be addressed. Email: maija.toropainen{at}ktl.fi.

	Abstract

Haemophilus influenzae (Hi) 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 Hi (NTHi) when 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 13-16 months, all infants receiving 3 or 4 doses of Pnc-PD had detectable anti-PD IgG antibodies and 36% (8/22) of the infants receiving 3 doses and 26% (6/23) of the infants receiving 4 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 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.