Recombinant Clostridium difficile toxin fragments as carrier protein for PSII surface polysaccharide preserve their neutralizing activity.
Clostridium difficile is a Gram-positive bacterium and is the most commonly diagnosed cause of hospital-associated and antimicrobial-associated diarrhea. Despite the emergence of epidemic C. difficile strains having led to an increase in the incidence of the disease, a vaccine against this pathogen is not currently available. C. difficile strains produce two main toxins (TcdA and TcdB) and express three highly complex cell-surface polysaccharides (PSI, PSII and PSIII). PSII is the more abundantly expressed by most C. difficile ribotypes offering the opportunity of the development of a carbohydrate-based vaccine. In this paper, we evaluate the efficacy, in naive mice model, of PSII glycoconjugates where recombinant toxins A and B fragments (TcdA_B2 and TcdB_GT respectively) have been used as carriers. Both glycoconjugates elicited IgG titers anti-PSII although only the TcdB_GT conjugate induced a response comparable to that obtained with CRM197. Moreover, TcdA_B2 and TcdB_GT conjugated to PSII retained the ability to elicit IgG with neutralizing activity against the respective toxins. These results are a crucial proof of concept for the development of glycoconjugate vaccines against C. difficile infection (CDI) that combine different C. difficile antigens to potentially prevent bacterial colonization of the gut and neutralize toxin activity.
Novartis Vaccines, Via Fiorentina 1, Siena 53100, Italy. maria_rosaria.romano@novartis.com.
Maria R
MR
Romano
Novartis Vaccines, Via Fiorentina 1, Siena 53100, Italy. rosanna.leuzzi@novartis.com.
Rosanna
R
Leuzzi
Novartis Vaccines Institute for Global Health, Via Fiorentina 1, Siena 53100, Italy. emilia.cappelletti@novartis.com.
Emilia
E
Cappelletti
Novartis Vaccines, Via Fiorentina 1, Siena 53100, Italy. marta.tontini@novartis.com.
Marta
M
Tontini
Novartis Vaccines, Via Fiorentina 1, Siena 53100, Italy. alberto.nilo@novartis.com.
Alberto
A
Nilo
Novartis Vaccines, Via Fiorentina 1, Siena 53100, Italy. daniela.proietti@novartis.com.
Daniela
D
Proietti
Novartis Vaccines, Via Fiorentina 1, Siena 53100, Italy. francesco.berti@novartis.com.
Francesco
F
Berti
Novartis Vaccines, Via Fiorentina 1, Siena 53100, Italy. paolo.costantino@novartis.com.
Paolo
P
Costantino
Novartis Vaccines, Via Fiorentina 1, Siena 53100, Italy. roberto.adamo@novartis.com.
Roberto
R
Adamo
Novartis Vaccines, Via Fiorentina 1, Siena 53100, Italy. maria.scarselli@novartis.com.
Maria
M
Scarselli
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016360:Clostridioides difficile / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004768:Enterotoxins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood*; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology; D013997:Time Factors; D018074:Vaccines, Conjugate / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D057134:Antibodies, Neutralizing; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D007074:Immunoglobulin G; D010446:Peptide Fragments; D011135:Polysaccharides, Bacterial; D011994:Recombinant Proteins; D018074:Vaccines, Conjugate; D014614:Vaccines, Synthetic; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile