**Author details**

Dodi Safari\* *Eijkman Institute for Molecular Biology, Jakarta, Indonesia* 

Ger Rijkers

626 The Complex World of Polysaccharides

3

incapability to induce the cytokines.

**Immunization1 IgG titer** 

**(Log10)2**

with CRM-neoglycoconjugate and supernatants were collected 72 h after culture initiation.

polysaccharide (Adopted from Safari, D. el at [85] with permission)

phagocytosis of *S. pneumoniae* type 14 [87].

**6. Future researches** 

polysaccharides are still unknown.

conclusion, the inability of polysaccharide to boost primed mice might be due to the

GC-GC 2.18±0.22 1022.3±275.2 571.2±20.0 GC-PS 0.34±0.47 0.3±0.5 66.1±0.4 GC-GC-GC 3.02±0.17 2700.4±112.3 1172.8±7.1 GC-PS-PS 0.0 0.0 664.9±221. Saline 0.0 6.9±1.1 0.0 1Five mice per group were immunized with a CRM-neoglycoconjugate (GC), a synthetic branched tetrasaccharide of Pn14PS that is conjugated to a CRM197 protein. Booster doses containing either a GC (GC-GC and GC-GC-GC) or a native polysaccharide of Pn14PS (PS) (GC-PS, GCGC-PS, and GC-PS-PS) were injected at Weeks 5 and 10.

2ELISA was employed to measure specific anti-Pn14PS IgG antibodies, and expressed as the log10 of the sera dilution

Cytokine levels in sera from mice receiving booster injection. Sera were collected on Day 1 after the primary immunization 4Splenocytes were isolated 7 days after the first booster injection. Spleen cells were cultured in vitro and stimulated

**Table 1.** Effect of booster immunization either with with either the same neoglycoconjugate or a native

**5.4. Improvement of anti-Pn14PS antibodies level by coadjuvant administration** 

The immunogenicity of neoglycoconjugate was increased with adjuvant coadministration [73, 86]. We set out to investigate in a mouse model the effect of adjuvant coadministration i.e. Quil-A, MPL, DDA, CpG and Alum on both the antibody- and cell-mediated immune response against a neoglycoconjugate as reported by Safari et al [87]. In the absence of adjuvant, immunization with neoglycoconjugate leads after a booster merely to IgG1 antibodies against PnP14PS. Coadministration of adjuvant had multiple effects: a diversified anti-Pn14PS IgG antibody response (also other IgG subclasses than IgG1 were evoked), an enhanced avidity and increased opsonic activity of these antibodies [87]. We found that next to Quil-A also DDA as a single dose or in combination with CpG had similar effects on the diversification of eliciting a broader variety of anti-Pn14PS IgG antibody subclasses. Meanwhile, CpG or alum on their own showed in majority IgG1 antibodies after booster immunization in a same pattern as in non adjuvant groups [87]. Compared to other adjuvants, codelivered Quil-A strongly improved the antibody avidity and enhanced the

In this review, synthetic oligosaccharide-protein conjugates are proven to be effective vaccines in mice model. A logical next step would be a feasibility and immunogenicity study in human volunteers. Before that, a study should be started with synthetic oligosaccharide-protein conjugates for at least the pneumococcal serotypes 1, 4, 5, 9V and 18C and should even have been completed, because the minimal epitopes for these

**Level of Cytokine IL-5 (pg/ml) In serum3 After stimulation4**

> *Department of Sciences, Roosevelt Academy, Middelburg and Department of Medical Microbiology and Immunology, St. Antonius Hospital, Nieuwegein, The Netherlands*

> Harm Snippe *Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands*
