Entirely Carbohydrate-Based Vaccines: An Emerging Field for Specific and Selective Immune Responses

Abstract

Carbohydrates are regarded as promising targets for vaccine development against infectious disease because cell surface glycans on many infectious agents are attributed to playing an important role in pathogenesis. In addition, oncogenic transformation of normal cells, in many cases, is associated with aberrant glycosylation of the cell surface glycan generating tumor associated carbohydrate antigens (TACAs). Technological advances in glycobiology have added a new dimension to immunotherapy when considering carbohydrates as key targets in developing safe and effective vaccines to combat cancer, bacterial infections, viral infections, etc. Many consider effective vaccines induce T-cell dependent immunity with satisfactory levels of immunological memory that preclude recurrence. Unfortunately, carbohydrates alone are poorly immunogenic as they do not bind strongly to the MHCII complex and thus fail to elicit T-cell immunity. To increase immunogenicity, carbohydrates have been conjugated to carrier proteins, which sometimes can impede carbohydrate specific immunity as peptide-based immune responses can negate antibodies directed at the targeted carbohydrate antigens. To overcome many challenges in using carbohydrate-based vaccine design and development approaches targeting cancer and other diseases, zwitterionic polysaccharides (ZPSs), isolated from the capsule of commensal anaerobic bacteria, will be discussed as promising carriers of carbohydrate antigens to achieve desired immunological responses.

Carbohydrate Conjugates in Vaccine Developments

“…However, a special group of polysaccharides, referred to as ZPSs, has been found to have the ability to induce MHC II mediated T cell response specifically (Kalka-Moll et al, 2002;Mazmanian and Kasper, 2006). At least eight different ZPSs have been isolated from Bacteroides fragilis, Staphylococcus aureus, and Streptococcus pneumoniae type 1, of which the PS A1 (isolated from Bacteroides fragilis) is the most studied ZPS so far (Scheme 1A) (Cobb and Kasper, 2005;Mazmanian and Kasper, 2006;Surana and Kasper, 2012;Nishat and Andreana, 2016).…”

A Leishmania murine model to evaluate the immunomodulatory properties of Pythium insidiosum proteins

“…A recent review on the use of immunotherapy to treat infectious and non-infectious diseases highlights the fascinating capabilities that some microbial proteins possess to modulate the immune response [34, 35, 36]. However, few immunotherapeutic proteins of microbial origin are presently being considered for immunotherapy; one of them is PiV, while the rest represent antigenic epitopes harvested from cancer patients [33, 37].…”

Glycoconjugate vaccines: some observations on carrier and production methods

“…Since the discovery by Cobb et al (2004) that PSA is able to prompt T-cell mediated immune responses, there have been successful applications of this knowledge towards development of all-carbohydrate vaccines, especially cancer vaccines (2012; De Silva, Wang, Chidley, Appulage, & Andreana, 2009;Nishat & Andreana, 2016;Trabbic et al, 2014), and regarding potential strategies for preventing inflammation using PSA-experienced T cells (Johnson, Jones, & Cobb, 2015b, highlighting the considerable future potential of using ZPS to control immune responses.…”