Chemoenzymatic Synthesis of 9NHAc-GD2 Antigen to Overcome the Hydrolytic Instability of O-Acetylated-GD2 for Anticancer Conjugate Vaccine Development

Angew Chem Int Ed Engl. 2021 Nov 2;60(45):24179-24188. doi: 10.1002/anie.202108610. Epub 2021 Oct 4.


Ganglioside GD2 is an attractive tumor-associated carbohydrate antigen for anti-cancer vaccine development. However, its low immunogenicity and the significant side effects observed with anti-GD2 antibodies present significant obstacles for vaccines. To overcome these, a new GD2 derivative bearing an N-acetamide (NHAc) at its non-reducing end neuraminic acid (9NHAc-GD2) has been designed to mimic the 9-O-acetylated-GD2 (9OAc-GD2), a GD2 based antigen with a restricted expression on tumor cells. 9NHAc-GD2 was synthesized efficiently via a chemoenzymatic method and subsequently conjugated with a powerful carrier bacteriophage Qβ. Mouse immunization with the Qβ-9NHAc-GD2 conjugate elicited strong and long-lasting IgG antibodies, which were highly selective toward 9NHAc-GD2 with little cross-recognition of GD2. Immunization of canines with Qβ-9NHAc-GD2 showed the construct was immunogenic in canines with little adverse effects, paving the way for future clinical translation to humans.

Keywords: 9NHAc-GD2; cancer; glycoconjugates; synthesis design; vaccine.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetamides / chemistry
  • Acetamides / immunology
  • Acetylation
  • Animals
  • Cancer Vaccines / chemistry*
  • Cancer Vaccines / immunology
  • Carbohydrate Conformation
  • Gangliosides / chemical synthesis*
  • Gangliosides / chemistry
  • Gangliosides / immunology
  • Hydrolysis
  • Mice
  • Neuraminic Acids / chemistry
  • Neuraminic Acids / immunology
  • Vaccine Development
  • Vaccines, Conjugate / chemistry*
  • Vaccines, Conjugate / immunology


  • Acetamides
  • Cancer Vaccines
  • Gangliosides
  • Neuraminic Acids
  • Vaccines, Conjugate
  • ganglioside, GD2
  • acetamide