Artikel ; Online: Immunogenicity and safety in rabbits of a Clostridioides difficile vaccine combining novel toxoids and a novel adjuvant.
2024 Band 42, Heft 7, Seite(n) 1582–1592
Abstract: Clostridioides difficile infection (CDI) is a serious healthcare-associated disease, causing symptoms such as diarrhea and pseudomembranous colitis. The major virulence factors responsible for the disease symptoms are two secreted cytotoxic proteins, ... ...
| Abstract | Clostridioides difficile infection (CDI) is a serious healthcare-associated disease, causing symptoms such as diarrhea and pseudomembranous colitis. The major virulence factors responsible for the disease symptoms are two secreted cytotoxic proteins, TcdA and TcdB. A parenteral vaccine based on formaldehyde-inactivated TcdA and TcdB supplemented with alum adjuvant, has previously been investigated in humans but resulted in an insufficient immune response. In search for an improved response, we investigated a novel toxin inactivation method and a novel, potent adjuvant. Inactivation of toxins by metal-catalyzed oxidation (MCO) was previously shown to preserve neutralizing epitopes and to annihilate reversion to toxicity. The immunogenicity and safety of TcdA and TcdB inactivated by MCO and combined with a novel carbohydrate fatty acid monosulphate ester-based (CMS) adjuvant were investigated in rabbits. Two or three intramuscular immunizations generated high serum IgG and neutralizing antibody titers against both toxins. The CMS adjuvant increased antibody responses to both toxins while an alum adjuvant control was effective only against TcdA. Systemic safety was evaluated by monitoring body weight, body temperature, and analysis of red and white blood cell counts shortly after immunization. Local safety was assessed by histopathologic examination of the injection site at the end of the study. Body weight gain was constant in all groups. Body temperature increased up to 1 ˚C one day after the first immunization but less after the second or third immunization. White blood cell counts, and percentage of neutrophils increased one day after immunization with CMS-adjuvanted vaccines, but not with alum. Histopathology of the injection sites 42 days after the last injection did not reveal any abnormal tissue reactions. From this study, we conclude that TcdA and TcdB inactivated by MCO and combined with CMS adjuvant demonstrated promising immunogenicity and safety in rabbits and could be a candidate for a vaccine against CDI. |
|---|---|
| Mesh-Begriff(e) | Animals ; Rabbits ; Adjuvants, Immunologic ; Alum Compounds ; Bacterial Proteins ; Bacterial Toxins ; Bacterial Vaccines/adverse effects ; Body Weight ; Boron Compounds ; Cephalosporins ; Clostridioides difficile ; Clostridium Infections/prevention & control ; Enterotoxins ; Toxoids |
| Chemische Substanzen | Adjuvants, Immunologic ; Alum Compounds ; aluminum sulfate (34S289N54E) ; Bacterial Proteins ; Bacterial Toxins ; Bacterial Vaccines ; Boron Compounds ; Cephalosporins ; Enterotoxins ; MCO (56369-20-1) ; Toxoids ; trimethylaminocarboxyldihydroboran |
| Sprache | Englisch |
| Erscheinungsdatum | 2024-02-09 |
| Erscheinungsland | Netherlands |
| Dokumenttyp | Journal Article |
| ZDB-ID | 605674-x |
| ISSN | 1873-2518 ; 0264-410X |
| ISSN (online) | 1873-2518 |
| ISSN | 0264-410X |
| DOI | 10.1016/j.vaccine.2024.01.076 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
Volltext online
Zusatzmaterialien
Kategorien
Verfügbar in ZB MED Köln/Königswinter
| Zs.A 1930: Hefte anzeigen | Standort: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
|||
| Zs.MO 458: Hefte anzeigen |
Über subito bestellen
Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.