**7. References**


<sup>\*</sup> Corresponding Author

oligosaccharides from acid and from enzymatic hydrolysates. Immunochemistry 1966;3:195-212.


[21] Bentley SD, Aanensen DM, Mavroidi A, Saunders D, Rabbinowitsch E, Collins M, Donohoe K, Harris D, Murphy L, Quail MA, Samuel G, Skovsted IC, Kaltoft MS, Barrell B, Reeves PR, Parkhill J, Spratt BG. Genetic analysis of the capsular biosynthetic locus from all 90 pneumococcal serotypes. PLoS.Genet. 2006;2(3):e31

628 The Complex World of Polysaccharides

1966;3:195-212.

1983;42(2):842-4.

J.Immunol. 1963;(91):633-40.

2012;doi:10.2217/NNM.11.151

2008;6(4):288-301.

children. Lancet 2005;365(9465):1147-52.

pneumonia. Lancet 2009;374(9700):1543-56.

polysaccharides: A chemical view. p. 81-114.

characterization. Microbiology 2010;156:555-60.

Clin.Microbiol 2007;45(4):1225-33.

gene. J Infect.Dis. 2010;202(1):29-38.

oligosaccharides from acid and from enzymatic hydrolysates. Immunochemistry

[6] Mage RG, Kabat EA. Immunochemical studies on dextrans: III. The specificities of rabbit antidextrans. Further findings on antidextrans with 1,2- and 1,6-specificities.

[9] Verez-Bencomo V, Fernandez-Santana V, Hardy E, Toledo ME, Rodriguez A, Baly A, Harrera L, Izquierdo M, Villar A, Valdes Y, Cosme K, Deler ML, Montane M, Gracia E, Ramos A, Aguilar A, Medina E, Torano G, Sosa I, Hernandez I, Martinez R, Muzachio A, Carmenates A, Costa L, Cardoso F, Campa C, Diaz V, Roy R. A synthetic conjugate polysaccharide vaccine against *Haemophilus influenzae* type b. Science 2004;305:522-5. [10] Safari D, Maradi M, Chiodo F, Dekker HA, Shan Y, Adamo R, Oscarson S, Rijkers GT, Lahmann M, Kamerling JP, Penades S, Snippe H. Gold nanoparticles as carriers for a synthetic *Streptococcus pneumoniae* type 14 conjugate vaccine. Nanomedicine

[11] Bryce J, Boschi-Pinto C, Shibuya K, Black RE. WHO estimates of the causes of death in

[12] World Health Organization. Pneumococcal conjugate vaccine for childhood immunization--WHO position paper. Wkly.Epidemiol.Rec. 2007;82(12):93-104. [13] Kadioglu A, Weiser JN, Paton JC, Andrew PW. The role of *Streptococcus pneumoniae* virulence factors in host respiratory colonization and disease. Nat.Rev.Microbiol

[14] de Velasco EA, Verheul AF, Verhoef J, Snippe H. *Streptococcus pneumoniae*: virulence

[15] van der PT, Opal SM. Pathogenesis, treatment, and prevention of pneumococcal

[16] Kamerling JP. Tomasz A, editors. *Streptococcus pneumoniae*, molecular biology & mechanisms of disease. New York: Mary Ann Liebert; 1999;Pneumococcal

[17] Park IH, Pritchard DG, Cartee R, Brandao A, Brandileone MC, Nahm MH. Discovery of a new capsular serotype (6C) within serogroup 6 of *Streptococcus pneumoniae*. J

[18] Bratcher PE, Kim KH, Kang JH, Hong JY, Nahm MH. Identification of natural pneumococcal isolates expressing serotype 6D by genetic, biochemical and serological

[19] Oftadeh S, Satzke C, Gilbert GL. Identification of the newly described *Streptococcus pneumoniae* serotype 6D using Quellung reaction and PCR. J Clin.Microbiol 2010; [20] Calix JJ, Nahm MH. A new pneumococcal serotype, 11E, has a variably inactivated wcjE

factors, pathogenesis, and vaccines. Microbiol.Rev. 1995;59(4):591-603.

[7] Kabat EA; Mayer MM. Experimental immunochemistry. IL, USA: Springfield; 1948. [8] Snippe H, van Dam JEG, van Houte AJ, Willers JMN, Kamerling JP, Vliegenthart JFG. Preparation of a semisynthetic vaccine to *Streptococcus pneumoniae* type 3. Infect.Immun.


[48] Whitney CG, Farley MM, Hadler J, Harrison LH, Bennett NM, Lynfield R, Reingold A, Cieslak PR, Pilishvili T, Jackson D, Facklam RR, Jorgensen JH, Schuchat A. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N.Engl.J.Med. 2003;348(18):1737-46.

630 The Complex World of Polysaccharides

Chemother. 2009;53(5):2066-73.

acquired pneumonia. BMC.Infect.Dis. 2009;9:36

Shanghai, China. Int.J.Antimicrob.Agents 2008;32(5):386-91.

conjugate vaccine coverage. JAMA 2007;297(16):1784-92.

Clin.Microbiol.Infect. 2008;14(9):876-9.

challenge. Vaccine 2007;25(16):2963-73.

2007;7(9):597-606.

BMC.Infect.Dis. 2007;7:119

[35] Siira L, Rantala M, Jalava J, Hakanen AJ, Huovinen P, Kaijalainen T, Lyytikainen O, Virolainen A. Temporal trends of antimicrobial resistance and clonality of invasive *Streptococcus pneumoniae* isolates in Finland, 2002 to 2006. Antimicrob.Agents

[36] Vila-Corcoles A, Bejarano-Romero F, Salsench E, Ochoa-Gondar O, de DC, Gomez-Bertomeu F, Raga-Luria X, Cliville-Guasch X, Arija V. Drug-resistance in *Streptococcus pneumoniae* isolates among Spanish middle aged and older adults with community-

[37] Imai S, Ito Y, Ishida T, Hirai T, Ito I, Maekawa K, Takakura S, Iinuma Y, Ichiyama S, Mishima M. High prevalence of multidrug-resistant Pneumococcal molecular epidemiology network clones among *Streptococcus pneumoniae* isolates from adult patients with community-acquired pneumonia in Japan. Clin.Microbiol.Infect. 2009; [38] Shibl AM. Distribution of serotypes and antibiotic resistance of invasive pneumococcal disease isolates among children aged 5 years and under in Saudi Arabia (2000-2004).

[39] Yang F, Xu XG, Yang MJ, Zhang YY, Klugman KP, McGee L. Antimicrobial susceptibility and molecular epidemiology of *Streptococcus pneumoniae* isolated from

[40] Gottlieb T, Collignon PJ, Robson JM, Pearson JC, Bell JM. Prevalence of antimicrobial resistances in *Streptococcus pneumoniae* in Australia, 2005: report from the Australian

[41] Barocchi MA, Censini S, Rappuoli R. Vaccines in the era of genomics: the pneumococcal

[42] O'Brien KL, Hochman M, Goldblatt D. Combined schedules of pneumococcal conjugate and polysaccharide vaccines: is hyporesponsiveness an issue? Lancet Infect.Dis.

[43] Singleton RJ, Hennessy TW, Bulkow LR, Hammitt LL, Zulz T, Hurlburt DA, Butler JC, Rudolph K, Parkinson A. Invasive pneumococcal disease caused by nonvaccine serotypes among alaska native children with high levels of 7-valent pneumococcal

[44] Douglas RM, Paton JC, Duncan SJ, Hansman DJ. Antibody response to pneumococcal vaccination in children younger than five years of age. J Infect.Dis. 1983;148(1):131-7. [45] Ortqvist A, Hedlund J, Burman LA, Elbel E, Hofer M, Leinonen M, Lindblad I, Sundelof B, Kalin M. Randomised trial of 23-valent pneumococcal capsular polysaccharide vaccine in prevention of pneumonia in middle-aged and elderly people. Swedish

[46] Teshale EH, Hanson D, Flannery B, Phares C, Wolfe M, Schuchat A, Sullivan P. Effectiveness of 23-valent polysaccharide pneumococcal vaccine on pneumonia in HIV-

[47] Veras MA, Enanoria WT, Castilho EA, Reingold AL. Effectiveness of the polysaccharide pneumococcal vaccine among HIV-infected persons in Brazil: a case control study.

Pneumococcal Vaccination Study Group. Lancet 1998;351(9100):399-403.

infected adults in the United States, 1998--2003. Vaccine 2008;26(46):5830-4.

Group on Antimicrobial Resistance. Commun.Dis.Intell. 2008;32(2):242-9.


induce protection against *Streptococcus pneumoniae* type 3 in mice. Infect.Immun. 2001;69(7):4698-701.


[73] Safari D, Dekker HA, Joosten JA, Michalik D, de Souza AC, Adamo R, Lahmann M, Sundgren A, Oscarson S, Kamerling JP, Snippe H. Identification of the smallest structure capable of evoking opsonophagocytic antibodies against *Streptococcus pneumoniae* type 14. Infect.Immun. 2008;76(10):4615-23.

632 The Complex World of Polysaccharides

2001;69(7):4698-701.

2009;27(1):69-77.

Vaccine 2009;27(39):5419-26.

1993;11(14):1429-36.

and rabbits. Vaccine 2002;20:19-21.

oligosaccharides. Science 2001;291(5508):1523-7.

*cholerae* O1, serotype Ogawa. Carbohydr.Res. 2005;340:2256-69.

Shigella flexneri 2a infection. J.Immunol. 2009;182(4):2241-7.

polysaccharide 23F IgG. Infect.Immun. 1994;62(3):799-808.

protective antibodies in mice. Infect.Immun. 2001;69(2):787-93.

induce protection against *Streptococcus pneumoniae* type 3 in mice. Infect.Immun.

[61] Plante OJ, Palmacci ER, Seeberger PH. Automated solid-phase synthesis of

[62] Saksena R, Ma X, Wade TK, Kovác P, Wade WF. Length of the linker and the interval between immunizations influences the efficacy of *Vibrio cholerae* O1,Ogawa hexasaccharide neoglycoconjugates. FEMS Immunol.Med.Microbiol. 2006;47:116-28. [63] Saksena R, Ma X, Wade TK, Kovac P, Wade WF. Effect of saccharide length on the immunogenicity of neoglycoconjugates from synthetic fragments of the O-SP of *Vibrio* 

[64] Bongat AF, Saksena R, Adamo R, Fujimoto Y, Shiokawa Z, Peterson DC, Fukase K, Vann WF, Kovac P. Multimeric bivalent immunogens from recombinant tetanus toxin H(C) fragment, synthetic hexasaccharides, and a glycopeptide adjuvant. Glycoconj.J.

[65] Phalipon A, Tanguy M, Grandjean C, Guerreiro C, Belot F, Cohen D, Sansonetti PJ, Mulard LA. A synthetic carbohydrate-protein conjugate vaccine candidate against

[66] Said HF, Phalipon A, Tanguy M, Guerreiro C, Belot F, Frisch B, Mulard LA, Schuber F. Rational design and immunogenicity of liposome-based diepitope constructs: application to synthetic oligosaccharides mimicking the Shigella flexneri 2a O-antigen.

[67] Schofield L, Hewitt MC, Evans K, Siomos MA, Seeberger PH. Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria. Nature 2002;418(6899):785-9. [68] Jeon I, Lee D, Krauss IJ, Danishefsky SJ. A new model for the presentation of tumorassociated antigens and the quest for an anticancer vaccine: a solution to the synthesis

[70] Jansen WT, Verheul AFM, Veeneman GH, van Boom JH, Snippe H. Revised interpretation of the immunological results obtained with pneumococcal polysaccharide 17F derived synthetic di-, tri- and tetrasaccharide conjugates in mice

[71] de Velasco EA, Verheul AF, van Steijn AM, Dekker HA, Feldman RG, Fernandez IM, Kamerling JP, Vliegenthart JF, Verhoef J, Snippe H. Epitope specificity of rabbit immunoglobulin G (IgG) elicited by pneumococcal type 23F synthetic oligosaccharideand native polysaccharide-protein conjugate vaccines: comparison with human anti-

[72] Jansen WT, Hogenboom S, Thijssen MJL, Kamerling JP, Vliegenthart JFG, Verhoef J, Snippe H, Verheul AFM. Synthetic 6B di-, tri-, and tetrasaccharide-protein conjugates contain pneumococcal type 6A and 6B common and 6B-specific epitopes that elicit

challenge via ring-closing metathesis. J.Am.Chem.Soc. 2009;131(40):14337-44. [69] de Velasco EA, Verheul AF, Veeneman GH, Gomes LJ, van Boom JH, Verhoef J, Snippe H. Protein-conjugated synthetic di- and trisaccharides of pneumococcal type 17F exhibit a different immunogenicity and antigenicity than tetrasaccharide. Vaccine


oligosaccharide-protein conjugate vaccines related to *Streptococcus pneumoniae* type 3. Infect.Immun. 2003;71(12):6915-20.

[87] Safari D, Dekker HA, Rijkers G, Snippe H. Codelivery of adjuvants at the primary immunization site is essential for evoking a robust immune response to neoglycoconjugates. Vaccine 2011;29(4):849-54.

Infect.Immun. 2003;71(12):6915-20.

neoglycoconjugates. Vaccine 2011;29(4):849-54.

oligosaccharide-protein conjugate vaccines related to *Streptococcus pneumoniae* type 3.

[87] Safari D, Dekker HA, Rijkers G, Snippe H. Codelivery of adjuvants at the primary immunization site is essential for evoking a robust immune response to
