Adjuvanted Modified Bacterial Antigens for Single-Dose Vaccines.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Adjuvants, Immunologic* ; Antigens, Bacterial*/immunology; Animals ; Mice ; Alum Compounds ; Tetanus Toxoid/immunology ; Female ; Adjuvants, Vaccine ; Bacterial Vaccines/immunology ; Mice, Inbred BALB C ; Salmonella typhi/immunology ; Antibodies, Bacterial/immunology

Alum is the most used vaccine adjuvant, due to its safety, low cost and adjuvanticity to various antigens. However, the mechanism of action of alum is complex and not yet fully understood, and the immune responses elicited can be weak and antigen-dependent. While several antigens rapidly desorb from alum upon exposure to serum, phosphorylated proteins remain tightly bound through a ligand-exchange reaction with surface hydroxyls on alum. Here, bacterial proteins and glycoconjugates have been modified with phosphoserines, aiming at enhancing the binding to alum and prolonging their bioavailability. Tetanus toxoid protein and Salmonella Typhi fragmented Vi-CRM conjugate were used. Both antigens rapidly and completely desorbed from alum after incubation with serum, verified via a competitive ELISA assay, and set up to rapidly evaluate in vitro antigen desorption from alum. After antigen modification with phosphoserines, desorption from alum was slowed down, and modified antigens demonstrated more prolonged retention at the injection sites through in vivo optical imaging in mice. Both modified antigens elicited stronger immune responses in mice, after a single injection only, compared to unmodified antigens. A stronger binding to alum could result in potent single-dose vaccine candidates and opens the possibility to design novel carrier proteins for glycoconjugates and improved versions of bacterial recombinant proteins.

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Keywords: alum; aluminium hydroxide; glycoconjugates; recombinant proteins; single dose; vaccines

0 (Adjuvants, Immunologic)
0 (Antigens, Bacterial)
0 (Alum Compounds)
0 (Tetanus Toxoid)
34S289N54E (aluminum sulfate)
0 (Adjuvants, Vaccine)
0 (Bacterial Vaccines)
0 (Antibodies, Bacterial)

Date Created: 20241109 Date Completed: 20241109 Latest Revision: 20241116

20241116

PMC11546299

10.3390/ijms252111461

39519015