Chapter 13 : Exploiting Molecular Mimicry in Targeting Carbohydrate Antigens

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Carbohydrate antigens are potential targets for preventive vaccination. However, carbohydrates alone are not capable of inducing a sufficient anamnestic or secondary immune response and require extensive adjuvanticity to convert them into T-cell-dependent (TD) antigens. This chapter reviews aspects of an alternative approach to induction of responses that target carbohydrate antigens by using peptide or polypeptide surrogates that mimic carbohydrate structures. Emphasis is on studies that elucidate basic mechanisms or immune parameters associated with vaccination with surrogates of glycosphingolipid constituents that may be applied to a variety of antigenic systems. The chapter shows that peptide mimotopes can induce cross-reactive carbohydrate responses that are able to protect mice from lethal bacterial infection or can induce humoral responses with components that are capable of binding to envelope glycoproteins of the human immunodeficiency virus, neutralizing cell-free virus. It illustrates that the Arg-containing peptides K61106 and K61107 also bind to the anti-sLeX Ab FH-6. Peptide mimics of carbohydrates may have several advantages over the carbohydrate itself for induction of carbohydrate-specific immunity: relative ease of production and induction of long-lasting, high-affinity IgG responses. Peptides that mimic carbohydrate structures have further significant advantages as vaccines compared with carbohydrate-protein conjugates or anti-Id Abs. Not all peptides identified as antigen mimics induce PS cross-reactive immune responses.

Citation: Cunto-Amesty G, Kieber-Emmons T. 2000. Exploiting Molecular Mimicry in Targeting Carbohydrate Antigens, p 175-196. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch13
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Table 1

Carbohydrate-based vaccines licensed or under development for bacteria and cancer

Citation: Cunto-Amesty G, Kieber-Emmons T. 2000. Exploiting Molecular Mimicry in Targeting Carbohydrate Antigens, p 175-196. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch13
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Table 2

Pneumococcal conjugate vaccines in phase II and phase III trials

Citation: Cunto-Amesty G, Kieber-Emmons T. 2000. Exploiting Molecular Mimicry in Targeting Carbohydrate Antigens, p 175-196. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch13
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Table 3

Peptide motifs that mimic carbohydrate structures

Citation: Cunto-Amesty G, Kieber-Emmons T. 2000. Exploiting Molecular Mimicry in Targeting Carbohydrate Antigens, p 175-196. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch13
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Table 4

Peptides described in our previous studies

Citation: Cunto-Amesty G, Kieber-Emmons T. 2000. Exploiting Molecular Mimicry in Targeting Carbohydrate Antigens, p 175-196. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch13
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Table 5

Similarities among neolactoseries constituents

Citation: Cunto-Amesty G, Kieber-Emmons T. 2000. Exploiting Molecular Mimicry in Targeting Carbohydrate Antigens, p 175-196. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch13
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Table 6

Secondary structure profiles of various MAb BR55-2-reactive and nonreactive peptides

Citation: Cunto-Amesty G, Kieber-Emmons T. 2000. Exploiting Molecular Mimicry in Targeting Carbohydrate Antigens, p 175-196. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch13
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Table 7

Kinetic analysis of ligand binding to MAb BR55-2

Citation: Cunto-Amesty G, Kieber-Emmons T. 2000. Exploiting Molecular Mimicry in Targeting Carbohydrate Antigens, p 175-196. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch13
Generic image for table
Table 8

Glycosphingolipid constituents shared among bacteria and tumor cells

Citation: Cunto-Amesty G, Kieber-Emmons T. 2000. Exploiting Molecular Mimicry in Targeting Carbohydrate Antigens, p 175-196. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch13

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