Synthesis, Liposomal Formulation, and Immunological Evaluation of a Minimalistic Carbohydrate-α-GalCer Vaccine Candidate

Broecker, Felix; Götze, Sebastian; Hudon, Jonathan; Rathwell, Dominea C. K.; Pereira, Claney L.; Stallforth, Pierre; Anish, Chakkumkal; Seeberger, Peter H.

doi:10.1021/acs.jmedchem.8b00312

Cited by 61 publications

(54 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 63 However, the relatively lower level of IgG3 compared to IgG1 is in stark contrast with the similar hierarchy of IgG1 and IgG3 induced by the vaccines against carbohydrate antigens. 53 , 64 − 66 This difference might be attributed mainly to the existence of the T helper epitope in the RBD-Fc region, 67 which is contained in vaccine candidates.…”

Section: Resultsmentioning

confidence: 99%

Potent Neutralizing Antibodies Elicited by RBD-Fc-Based COVID-19 Vaccine Candidate Adjuvanted by the Th2-Skewing iNKT Cell Agonist

Wang

Zhang

et al. 2021

J. Med. Chem.

View full text Add to dashboard Cite

The development of a safe and effective COVID-19 vaccine is of paramount importance to terminate the current pandemic. An adjuvant is crucial for improving the efficacy of the subunit COVID19 vaccine. α-Galactosylceramide (αGC) is a classical iNKT cell agonist which causes the rapid production of Th1- and Th2-associated cytokines; we, therefore, expect that the Th1- or Th2-skewing analogues of αGC can better enhance the immunogenicity of the receptor-binding domain in the spike protein of SARS-CoV-2 fused with the Fc region of human IgG (RBD-Fc). Herein, we developed a universal synthetic route to the Th1-biasing (α-C-GC) and Th2-biasing (OCH and C20:2) analogues. Immunization of mice demonstrated that αGC-adjuvanted RBD-Fc elicited a more potent humoral response than that observed with Alum and enabled the sparing of antigens. Remarkably, at a low dose of the RBD-Fc protein (2 μg), the Th2-biasing agonist C20:2 induced a significantly higher titer of the neutralizing antibody than that of Alum.

show abstract

Section: Resultsmentioning

confidence: 99%

Potent Neutralizing Antibodies Elicited by RBD-Fc-Based COVID-19 Vaccine Candidate Adjuvanted by the Th2-Skewing iNKT Cell Agonist

Wang

Zhang

et al. 2021

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

“…In this case, α-GalCer served as a liposomal carrier as well as an adjuvant for iNKT cell activation. In a later study from the Seeberger lab, the liposomal form of Tn-α-GalCer conjugates showed effective activation of anti-Tn immunity in vivo (Broecker et al, 2018). Compared to Tn-CRM 197 , a protein carrier-based vaccine, the anti-Tn IgG response generated by the liposomal form of Tnα-GalCer conjugate was more consistent and more specific.…”

Section: α-Galactosylceramide (α-Galcer)mentioning

confidence: 95%

Carbohydrate Conjugates in Vaccine Developments

Lang

Huang

2020

Front. Chem.

View full text Add to dashboard Cite

Vaccines are powerful tools that can activate the immune system for protection against various diseases. As carbohydrates can play important roles in immune recognition, they have been widely applied in vaccine development. Carbohydrate antigens have been investigated in vaccines against various pathogenic microbes and cancer. Polysaccharides such as dextran and β-glucan can serve as smart vaccine carriers for efficient antigen delivery to immune cells. Some glycolipids, such as galactosylceramide and monophosphoryl lipid A, are strong immune stimulators, which have been studied as vaccine adjuvants. In this review, we focus on the current advances in applying carbohydrates as vaccine delivery carriers and adjuvants. We will discuss the examples that involve chemical modifications of the carbohydrates for effective antigen delivery, as well as covalent antigen-carbohydrate conjugates for enhanced immune responses.

show abstract

“…24,25 It has been reported that α-GalCer has been used to develop vaccines by conjugating with antigen epitopes, such as carbohydrate antigens. [26][27][28][29][30] peptide antigens [31][32][33] and nicotine antigen. 34 Gold nanoparticles (AuNPs) have been served as a nanocarrier for the multivalent presentation of tumor associate antigens.…”

Section: Introductionmentioning

confidence: 99%

The Adjuvant of α-Galactosylceramide Presented by Gold Nanoparticles Enhances Antitumor Immune Responses of MUC1 Antigen-Based Tumor Vaccines

Liu¹,

Wang²,

Fan³

et al. 2021

IJN

View full text Add to dashboard Cite

Background: Therapeutic tumor vaccines are one of the most promising strategies and have attracted great attention in cancer treatment. However, most of them have shown unsatisfactory immunogenicity, there are still few available vaccines for clinical use. Therefore, there is an urgent demand to develop novel strategies to improve the immune efficacy of antitumor vaccines. Purpose: This study aimed to develop novel adjuvants and carriers to enhance the immune effect of MUC1 glycopeptide antigen-based antitumor vaccines. Methods: An antitumor vaccine was developed, in which MUC1 glycopeptide was used as tumor-associated antigen, α-GalCer served as an immune adjuvant and AuNPs was a multivalent carrier. Results: Immunological evaluation results indicated that the constructed vaccines enabled a significant antibody response. FACS analysis and immunofluorescence assay showed that the induced antisera exhibited a specific binding with MUC1 positive MCF-7 cells. Moreover, the induced antibody can mediate CDC to kill MCF-7 cells. Besides stimulating B cells to produce MUC1-specific antibodies, the prepared vaccines also induced MUC1-specific CTLs in vitro. Furthermore, the vaccines significantly delayed tumor development in tumor-bearing mice model. Conclusion: These results showed that the construction of vaccines by presenting α-GalCer adjuvant and an antigen on gold nanoparticles offers a potential strategy to improve the antitumor response in cancer immunotherapy.

show abstract

Synthesis, Liposomal Formulation, and Immunological Evaluation of a Minimalistic Carbohydrate-α-GalCer Vaccine Candidate

Cited by 61 publications

References 49 publications

Potent Neutralizing Antibodies Elicited by RBD-Fc-Based COVID-19 Vaccine Candidate Adjuvanted by the Th2-Skewing iNKT Cell Agonist

Potent Neutralizing Antibodies Elicited by RBD-Fc-Based COVID-19 Vaccine Candidate Adjuvanted by the Th2-Skewing iNKT Cell Agonist

Carbohydrate Conjugates in Vaccine Developments

The Adjuvant of α-Galactosylceramide Presented by Gold Nanoparticles Enhances Antitumor Immune Responses of MUC1 Antigen-Based Tumor Vaccines

Contact Info

Product

Resources

About