Synthesis and evaluation of monophosphoryl lipid A derivatives as fully synthetic self-adjuvanting glycoconjugate cancer vaccine carriers.

Abstract

A fully synthetic carbohydrate-based cancer vaccine is an attractive concept, but an important topic in the area is to develop proper vaccine carriers that can improve the immunogenicity and other immunological properties of tumor-associated carbohydrate antigens (TACAs). In this context, four monophosphoryl derivatives of Neisseria meningitidis lipid A were synthesized via a highly convergent and effective strategy and evaluated as vaccine carriers and adjuvants. The conjugates of these monophosphoryl lipid A (MPLA) derivatives with a modified form of the sTn antigen were found to elicit high titers of antigen-specific IgG antibodies, indicating a T cell-dependent immune response, in the absence of an external adjuvant. It was concluded that MPLAs could be utilized as potent vaccine carriers and built-in adjuvants to create fully synthetic self-adjuvanting carbohydrate-based cancer vaccines. The lipid composition and structure of MPLA were shown to have a significant influence on its immunological activity, and among the MPLAs examined, natural N. meningitidis MPLA exhibited the most promising properties. Moreover, Titermax Gold, a conventional vaccine adjuvant, was shown to inhibit, rather than promote, the immunological activity of MPLA conjugates, maybe via interacting with MPLA.

• Authors: Zhifang Zhou, Mohabul Mondal, Guochao Liao, Zhongwu Guo
• Journal: Organic & biomolecular chemistry (Org Biomol Chem) Vol. 12 Issue 20 Pg. 3238-45 (May 28 2014) ISSN: 1477-0539 [Electronic] England
• PMID: 24728423 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• 5'-N-phenylacetyl siayl Tn antigen
• Adjuvants, Immunologic
• Antigens, Tumor-Associated, Carbohydrate
• Cancer Vaccines
• Drug Carriers
• Glycoconjugates
• Immune Sera
• Lipid A
• Vaccines, Synthetic
• monophosphoryl lipid A

Topics

• Adjuvants, Immunologic (chemical synthesis, chemistry)
• Animals
• Antigens, Tumor-Associated, Carbohydrate (immunology)
• Cancer Vaccines (chemical synthesis, chemistry, immunology)
• Drug Carriers (chemistry)
• Enzyme-Linked Immunosorbent Assay
• Glycoconjugates (immunology)
• Immune Sera
• Lipid A (analogs & derivatives, chemical synthesis, chemistry, immunology)
• Mice
• Neisseria
• Vaccines, Synthetic (immunology)