17041-36-0Relevant articles and documents
Structure Guided Design of Bacteriophage Qβ Mutants as Next Generation Carriers for Conjugate Vaccines
Huang, Xuefei,Jin, Xiangshu,Kavunja, Herbert,Lang, Shuyao,Lin, Po-Han,McFall-Boegeman, Hunter,Ramadan, Sherif,Rashidijahanabad, Zahra,Shaw, Vincent,Sungsuwan, Suttipun,Tahmasebi Nick, Setare,Tan, Zibin,Wu, Xuanjun,Yin, Zhaojun
, (2022/02/23)
Vaccines are critical tools to treat and prevent diseases. For an effective conjugate vaccine, the carrier is crucial, but few carriers are available for clinical applications. In addition, a drawback of current protein carriers is that high levels of antibodies against the carrier are induced by the conjugate vaccine, which are known to interfere with the immune responses against the target antigen. To overcome these challenges, we obtained the near atomic resolution crystal structure of an emerging protein carrier, i.e., the bacteriophage Qβ virus like particle. On the basis of the detailed structural information, novel mutants of bacteriophage Qβ (mQβ) have been designed, which upon conjugation with tumor associated carbohydrate antigens (TACAs), a class of important tumor antigens, elicited powerful anti-TACA IgG responses and yet produced lower levels of anticarrier antibodies as compared to those from the wild type Qβ-TACA conjugates. In a therapeutic model against an aggressive breast cancer in mice, 100% unimmunized mice succumbed to tumors in just 12 days even with chemotherapy. In contrast, 80% of mice immunized with the mQβ-TACA conjugate were completely free from tumors. Besides TACAs, to aid in the development of vaccines to protect against COVID-19, the mQβ based conjugate vaccine has been shown to induce high levels of IgG antibodies against peptide antigens from the SARS-CoV-2 virus, demonstrating its generality. Thus, mQβ is a promising next-generation carrier platform for conjugate vaccines, and structure-based rational design is a powerful strategy to develop new vaccine carriers.
COMPOSITIONS AND METHODS OF TREATING CANCER AND INFECTIONS USING BACTERIOPHAGE AND ITS MUTANTS
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Page/Page column 8; 66, (2019/03/17)
Provided herein are vaccine composition comprising an antigen conjugated to a capsid, wherein the capsid comprises wild type or native sequence. Provided herein are also vaccine composition comprising an antigen conjugated to a capsid, wherein said capsid comprises at least one mutation, such as a non-natural mutation. Such compositions are useful in the treatment and prevention of pathogenic infections, inflammatory diseases, and neurodegenerative disease, and cancer, among others.
Stereoselective synthesis of natural and non-natural thomsen-nouveau antigens and hydrazide derivatives
Shaik, Ahmad Ali,Nishat, Sharmeen,Andreana, Peter R.
supporting information, p. 2582 - 2585 (2015/06/16)
A selective glycosylation strategy enabling access to all stereochemical combinations of tumor associated Thomsen-nouveau (Tn) antigen, d-GalNAc-O-Ser/Thr, has been developed. The key component for selectivity is the phthalimide-protected d- or l-amino acid acceptors which allow access to α- or β-anomers in excellent yields (72-96%) and selectivity (～100%) when appropriate C-2 substitution is installed. The glycoamino acid intermediates were divergently converted to Tn-based carboxylates or to hydrazides by tandem Pd-C debenzylation followed by treatment with hydrazine hydrate or hydrazine hydrate treatment alone.
