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Infection and Immunity, December 2003, p. 6915-6920, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6915-6920.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Th1-Directing Adjuvants Increase the Immunogenicity of Oligosaccharide-Protein Conjugate Vaccines Related to Streptococcus pneumoniae Type 3

Dirk J. Lefeber,1* Barry Benaissa-Trouw,1 Johannes F. G. Vliegenthart,2 Johannis P. Kamerling,2 Wouter T. M. Jansen,1 Kees Kraaijeveld,1 and Harm Snippe1

Vaccines Section, Eijkman-Winkler Institute for Microbiology, Infectious Diseases and Inflammation, University Medical Center, 3584 CX Utrecht,1 Section of Glycoscience and Biocatalysis, Department of Bio-Organic Chemistry, Bijvoet Center, Utrecht University, 3584 CH Utrecht,The Netherlands2

Received 1 April 2003/ Returned for modification 23 May 2003/ Accepted 18 July 2003

Oligosaccharide (OS)-protein conjugates are promising candidate vaccinesagainst encapsulated bacteria, such as Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae. Although the effects of several variables such as OS chain length and protein carrier have been studied, little is known about the influence of adjuvants on the immunogenicity of OS-protein conjugates. In this study, a minimal protective trisaccharide epitope of Streptococcus pneumoniae type 3 conjugated to the cross-reacting material of diphtheria toxin was used for immunization of BALB/c mice in the presence of different adjuvants. Subsequently, half of the mice received a booster immunization with conjugate alone. Independent of the use and type of adjuvant, all mice produced long-lasting anti-polysaccharide type 3 (PS3) antibody levels, which provided full protection against challenge with pneumococcal type 3 bacteria. All adjuvants tested increased the anti-PS3 antibody levels and opsonic capacities as measured by an enzyme-linked immunosorbent assay and an in vitro phagocytosis assay. The use of QuilA or a combination of the adjuvants CpG and dimethyl dioctadecyl ammonium bromide resulted in the highest phagocytic capacities and the highest levels of Th1-related immunoglobulin G (IgG) subclasses. Phagocytic capacity correlated strongly with Th1-associated IgG2a and IgG2b levels, to a lesser extent with Th2-associated IgG1 levels, and weakly with thiocyanate elution as a measure of avidity. Thus, the improved immunogenicity of OS-protein conjugates was most pronounced for Th1-directing adjuvants.

* Corresponding author. Mailing address: Eijkman-Winkler Institute for Microbiology, Infectious Diseases and Inflammation, Vaccines Section, University Medical Center, 3584 CX Utrecht, The Netherlands. Phone: 31 30 2506534. Fax: 31 302541770. E-mail: D.J.Lefeber{at}lab.azu.nl.

Editor: J. N. Weiser

Infection and Immunity, December 2003, p. 6915-6920, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6915-6920.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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