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Application US20210085781
Published 2021-03-25
Neoglycoconjugates As Vaccines And Therapeutic Tools
Neoglycoconjugates as immunogens and therapeutic/diagnostic tools are described herein. The neoglycoconjugates are produced by conjugating a carbohydrate antigen intermediate to a free amine group of a carrier material (e.g., carrier protein). The intermediate comprises a linker having a first end and a second end, the first end being conjugated to a carbohydrate antigen via a thio ether bond and the second end comprising a functional group reactable with a free amine group. Following coupling, the carbohydrate antigen becomes covalently bound to the carrier material via an amide, a carbamate, a sulfonamide, a urea, or a thiourea bond, thereby producing the neoglycoconjugate. Applications of the neoglycoconjugates as antigens, immunogens, vaccines, and in diagnostics are also described. Specifically, the use of (neo)glycoconjugates as vaccine candidates and other therapeutic tools against cancers, viruses such as SARS-CoV-2, and other diseases characterized by expression of aberrant glycosylation are also described.
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- 1. A process for triggering the production of anti-SARS-CoV-2 antibodies in a subject, the process comprising: providing an immunogenic glycoconjugate comprising one or more carbohydrate antigens conjugated to a carrier protein or peptide, wherein the one or more carbohydrate antigens comprise or consist of unsialylated Thomsen-Friedenreich (TF) antigen, sialylated TF antigen, unsialylated Tn antigen, sialylated Tn antigen, or any combination thereof, and administering the glycoconjugate to the subject with a suitable adjuvant such that antibodies are produced that bind to the one or more carbohydrate antigens present on glycosylated spike (S) protein expressed on SARS-CoV-2 virions.
- 19. A method of treating or reducing the risk of SARS-CoV-2 viral infection in a subject, the method comprising administering to the subject one or more ligands having binding specificity for an O-linked glycan expressed on the SARS-CoV-2 S protein, wherein the O-linked glycan is sialylated TF antigen, unsialylated TF antigen, sialylated Tn antigen, or unsialylated Tn antigen, and wherein the ligand is an antibody, an antibody fragment, or a lectin.
- 20. An immune complex comprising a SARS-CoV-2 S protein or fragment thereof, expressing an O-linked glycan bound to a ligand having binding specificity for said O-linked glycan, wherein the O-linked glycan is sialylated TF antigen, unsialylated TF antigen, sialylated Tn antigen, or unsialylated Tn antigen, and wherein the ligand is an antibody, an antibody fragment, or a lectin.
