A fully synthetic self-adjuvanting cancer vaccine candidate was constructed through covalent conjugation of invariant natural killer T (iNKT) cell ligand α-galactosylceramide (αGalCer) with sialyl Tn (STn), a representative tumor-associated carbohydrate antigen (TACA). This two-component vaccine STn-αGalCer is devoid of antigenic peptide, featuring the well-defined structure with high simplicity. STn-αGalCer showed remarkable efficacy in inducing antibody class switching from IgM to STn-specific IgG. Subtypes of IgG antibody were primarily IgG1 and IgG3.
Porous single-crystal-like CdS nanosheets fabricated through a facile cation-exchange strategy exhibit a noticeable photocatalytic activity for aerobic oxidative coupling of amines to imines with 1 atm O 2 under visible-light irradiation (l > 420 nm) at room temperature.
The tumor‐associated antigen mucin 1 (MUC1) has been pursued as an attractive target for cancer immunotherapy, but the poor immunogenicity of the endogenous antigen hinders the development of vaccines capable of inducing effective anti‐MUC1 immunodominant responses. Herein, we prepared synthetic anti‐MUC1 vaccines in which the hydrophilic MUC1 antigen was N‐terminally conjugated to one or two palmitoyl lipid chains (to form amphiphilic Pam‐MUC1 or Pam2‐MUC1). These amphiphilic lipid‐tailed MUC1 antigens were self‐assembled into liposomes containing the NKT cell agonist αGalCer as an adjuvant. The lipid‐conjugated antigens reshaped the physical and morphological properties of liposomal vaccines. Promising results showed that the anti‐MUC1 IgG antibody titers induced by the Pam2‐MUC1 vaccine were more than 30‐ and 190‐fold higher than those induced by the Pam‐MUC1 vaccine and the MUC1 vaccine without lipid tails, respectively. Similarly, vaccines with the TLR1/2 agonist Pam3CSK4 as an adjuvant also induced conjugated lipid‐dependent immunological responses. Moreover, vaccines with the αGalCer adjuvant induced significantly higher titers of IgG antibodies than vaccines with the Pam3CSK4 adjuvant. Therefore, the non‐covalent assembly of the amphiphilic lipo‐MUC1 antigen and the NKT cell agonist αGalCer as a glycolipid adjuvant represent a synthetically simple but immunologically effective approach for the development of anti‐MUC1 cancer vaccines.
Safe and effective vaccines against severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) and its variants are the best approach to successfully combat the COVID-19
pandemic. The receptor-binding domain (RBD) of the viral spike protein is a major target
to develop candidate vaccines. α-Galactosylceramide (αGalCer), a potent
invariant natural killer T cell (iNKT) agonist, was site-specifically conjugated to the
N
-terminus of the RBD to form an adjuvant–protein conjugate,
which was anchored on the liposome surface. This is the first time that an iNKT cell
agonist was conjugated to the protein antigen. Compared to the unconjugated
RBD/αGalCer mixture, the αGalCer-RBD conjugate induced significantly
stronger humoral and cellular responses. The conjugate vaccine also showed effective
cross-neutralization to all variants of concern (B.1.1.7/alpha, B.1.351/beta, P.1/gamma,
B.1.617.2/delta, and B.1.1.529/omicron). These results suggest that the self-adjuvanting
αGalCer-RBD has great potential to be an effective COVID-19 vaccine candidate, and
this strategy might be useful for designing various subunit vaccines.
The coronavirus 2019 (COVID-19) pandemic is causing serious impact in the world, safe and effective vaccines and medicines are the best method to combat the disease. The receptor-binding domain (RBD)...
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