Testing a Recombinant Form of Tetanus Toxoid as a Carrier Protein for Glycoconjugate Vaccines

Autor: Davide Oldrini, Roberta Di Benedetto, Martina Carducci, Daniele De Simone, Luisa Massai, Renzo Alfini, Barbara Galli, Brunella Brunelli, Amanda Przedpelski, Joseph T. Barbieri, Omar Rossi, Carlo Giannelli, Rino Rappuoli, Francesco Berti, Francesca Micoli
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Vaccines, Vol 11, Iss 12, p 1770 (2023)
Druh dokumentu: article
ISSN: 2076-393X
05639875
DOI: 10.3390/vaccines11121770
Popis: Glycoconjugate vaccines play a major role in the prevention of infectious diseases worldwide, with significant impact on global health, enabling the polysaccharides to induce immunogenicity in infants and immunological memory. Tetanus toxoid (TT), a chemically detoxified bacterial toxin, is among the few carrier proteins used in licensed glycoconjugate vaccines. The recombinant full-length 8MTT was engineered in E. coli with eight individual amino acid mutations to inactivate three toxin functions. Previous studies in mice showed that 8MTT elicits a strong IgG response, confers protection, and can be used as a carrier protein. Here, we compared 8MTT to traditional carrier proteins TT and cross-reactive material 197 (CRM197), using different polysaccharides as models: Group A Streptococcus cell-wall carbohydrate (GAC), Salmonella Typhi Vi, and Neisseria meningitidis serogroups A, C, W, and Y. The persistency of the antibodies induced, the ability of the glycoconjugates to elicit booster response after re-injection at a later time point, the eventual carrier-induced epitopic suppression, and immune interference in multicomponent formulations were also evaluated. Overall, immunogenicity responses obtained with 8MTT glycoconjugates were compared to those obtained with corresponding TT and, in some cases, were higher than those induced by CRM197 glycoconjugates. Our results support the use of 8MTT as a good alternative carrier protein for glycoconjugate vaccines, with advantages in terms of manufacturability compared to TT.
Databáze: Directory of Open Access Journals
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