Table 1.
Immune-based treatment and prevention of Clostridium difficile infection
| Model | Antigen | Antibody | Route of administration | Treatment method | Outcome | Reference |
|---|---|---|---|---|---|---|
| Hamster | TcdA and TcdB | Mouse mAb PCG-4 specific to toxin A; G-2 specific to toxin B |
Oral | Animals were pretreated with 1 M NaHCO3 and treated with MAb and toxin mixture and observed for 72 hrs | PCG-4 MAb neutralized the effects of toxin A | 105 |
| Hamster | TcdA and TcdB | Sheep (ovine) IgG specific against recombinant toxin A and toxin B polypeptide of C. difficile VPI 10,463 | Oral | Ovine antibody (IgG) doses of 2.5 and 25 mg was administered on the days 0 (before challenge), then day 3 and 6 (post challenge) | 90 and 40% of the animals survived in the high- and low-antibody-dose groups respectively and at 12 days post challenge all surviving animals were asymptomatic | 106 |
| Hamster | TcdA and TcdB | Humanized mAbs (IgG1) | Oral | Animals were predosed by intraperitoneal (i.p.) inoculation with mAb mixtures once/day for 4 days (days −3, −2, −1 and 0) – two doses of mAb – 50 mg/kg (high dose) and 5 mg/kg (low dose) of each anti-TcdA and anti-TcdB | High dose mAbs showed 100% protection on day 11 and ∼82% (9/11) survival rate until end of the study on day 28. Low dose mAbs showed 100% protective effect only until day 3 then slowly succumbed to infection | 91 |
| Hamster | TcdA and TcdB + whole bacterium | Immune whey protein concentrate (WPC-40, Mucomilk) | Oral | Before and after challenge, then every 8 hrs during 10 days | 80–90% protection | 107 |
| CDI patients | Three times daily for 2 weeks after antibiotic treatment | Significant decrease of recurrences | 108 | |||
| Randomized double-blind study in CDI patients | Formalin inactivated C. difficile cells | Immune whey IgG concentrate (CDIW) | Oral | Three times daily, 14 days | As effective as metronidazole in the prevention of recurrences | 109 |
| Mouse model of infection and relapse | TcdB-C-ter, inactivated spores, exosporium, inactivated vegetative cells, SLP | Hyper-immune bovine colostrum TcdB-HBC, mixture 1-HBC, mixture 2-HBC | Oral | Two days before challenge and throughout experiment | HBC-TcdB alone or in combination (Mix1 and Mix2-HBC) prevents and treats CDI in mice and reduces recurrences | 110 |
| Hamster | LMW- and HMW-SLPs | Rabbit hyper- immune serum | Oral | Seven hour before challenge, during challenge, then 6, 17 and 24 hrs after challenge | Prolonged survival after challenge but no protection against death | 111 |
| Mouse | FliC | Mouse hyper- immune serum | Intra-peritoneal | Twenty four hour before challenge | Eighty percent of protection | 112 |
Abbreviations: TcdA, toxin A; TcdB, toxin B; PCG-4, mouse monoclonal anti-Clostridium difficile toxin A antibody; G-2, immunoglobulin 2; MAb, monoclonal antibodies; IgG, Immunoglobulin G; VPI 10,463, Clostridium difficile strain VPI 10,463; WPC-40, whey protein concentrate 40%; CDIW, Immune whey IgG concentrate; TcdB-HBC, toxin B-hyperimmune bovine colostrum; HBC, hyperimmune bovine colostrum; HMW, high-molecular-weight; LMW, low-molecular-weight; SLPs, surface layer proteins.