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Induction of Immunologic Memory Following Primary Vaccination With the 10-valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine in Infants

Knuf, Markus MD*,†; Pankow-Culot, Heidemarie MD; Grunert, Detlef MD§; Rapp, Michael MD; Panzer, Falko MD; Köllges, Ralph MD**; Fanic, Aurélie MSc††; Habib, Ahsan MIPH††; Borys, Dorota MD††; Dieussaert, Ilse IR††; Schuerman, Lode MD††

Pediatric Infectious Disease Journal: January 2012 - Volume 31 - Issue 1 - p e31–e36
doi: 10.1097/INF.0b013e3182323ac2
Vaccine Reports

Background: Induction of immunologic memory was assessed following primary vaccination with 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV).

Methods: Infants were randomized (1:1) to receive 3 doses of PHiD-CV or 7vCRM (7-valent CRM197-conjugated pneumococcal conjugate vaccine [PCV]) at 2, 3, and 4 months of age followed by 23-valent pneumococcal polysaccharide vaccine (23vPS) booster dose at 11 to 14 months of age. Pneumococcal geometric mean antibody concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers were measured.

Results: Postprimary immune responses were consistent with those in previous PHiD-CV and 7vCRM studies. Following 23vPS boosting, vaccine serotype-specific antibody GMCs increased 6.5- to 33.3-fold and 4.8- to 32.2-fold versus prebooster in the PHiD-CV and 7vCRM groups, respectively. Postbooster OPA titers increased 2.8- to 38.8-fold and 2.6- to 58.9-fold, respectively. Postbooster antibody GMCs exceeded postprimary levels but, for some serotypes, postbooster OPA geometric mean titers were lower than postprimary in both groups. An additional dose of the same PCV received for priming was administered to 52 children aged 46 to 50 months, resulting in higher responses versus postprimary vaccination for all serotypes, but not always higher than post-23vPS booster.

Conclusions: Induction of immunologic memory following PHiD-CV priming was confirmed. Additional PCV boosting in 4-year-olds did not provide strong evidence of hyporesponsiveness induced by previous 23vPS boosting. However, our results did not rule out depletion of the memory B cell pool following 23vPS vaccination, resulting in subsequent attenuated immune responses, and therefore support the use of PCV rather than 23vPS for booster vaccination in the second year of life.

From the *Zentrum für Kinder- und Jugendmedizin, Johannes Gutenberg Universität Mainz, University Medicine Mainz, Germany; †Dr. Horst Schmidt Klinik, Children's Hospital, Wiesbaden, Germany; ‡Pediatric Office, Heiligenhaus, Germany; §Praxis, Nordlingen, Germany; ¶Pediatric Practice, Willich, Germany; ∥Pediatric Office, Mannheim-Neckarstadt, Germany; **Praxis für Kinder und Jugendliche, Mönchengladbach (Rheydt), Germany; and ††Global Vaccine Development, GlaxoSmithKline Biologicals, Wavre, Belgium. Wavre, Belgium.

Accepted for publication July 19, 2011.

GlaxoSmithKline Biologicals was involved in all stages of the study conduct and analysis. GlaxoSmithKline Biologicals also took in charge all costs associated to the development and the publishing of the present manuscript. The corresponding author had full access to the data and final responsibility for submission of the publication.

Prevenar/Prevnar is a trademark of Pfizer Inc.; Synflorix and Infanrix hexa are trademarks of the GlaxoSmithKline group of companies; Pneumovax23 is a trademark of Merck & Co., Inc.

Supported by GlaxoSmithKline Biologicals, Rixensart, Belgium (study numbers: 105554, 106623, 112807; www.ClinicalTrials.gov: NCT00307541, NCT00333450, NCT00907777). M.K. has received travel grants, honoraria for presentations and consultancy from GlaxoSmithKline Biologicals. M.R. and H.P.C. declare that their practices have received compensation for the work reported here. F.P., D.G., and R.K. have no conflicts of interest. A.H., D.B., I.D., and L.S. are employed by GlaxoSmithKline Biologicals and have stock ownership; A.F. works as a consultant for GlaxoSmithKline Biologicals.

The authors have no other funding or conflicts of interest to disclose.

Address for correspondence: Markus Knuf, MD, Dr. Horst Schmidt Klinik, Children's Hospital, Ludwig-Erhard-Strasse 100, 65199 Wiesbaden, Germany; or Pediatric Infectious Diseases, University Medicine, Langenbeckstrasse 1, 55101 Mainz, Germany. E-mail: markus.knuf@hsk-wiesbaden.de.

© 2012 Lippincott Williams & Wilkins, Inc.