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Immunoglobulin	2
Antitoxin	1

The most common world-wide cause of antibiotic-associated infectious diarrhea and colitis is the toxin producing bacterium, Clostridioides difficile (C. difficile). Here we review the background and characteristics of the bacterium and the toxins produced together with the epidemiology and the complex pathogenesis that leads to a broad clinical spectrum of disease. The review describes the difficulties faced in obtaining a quick and accurate diagnosis despite the range of sensitive and specific diagnostic tools available. We also discuss the problem of disease recurrence and the importance of disease prevention. The high rates of infection recurrence mean that treatment strategies are constantly under review and we outline the diverse treatment options that are currently in use and explore the emerging treatment options of pulsed antibiotic use, microbial replacement therapies and the use of monoclonal antibodies. We summarize the future direction of treatment strategies which include the development of novel antibiotics, the administration of oral polyclonal antibody formulations, the use of vaccines, the administration of competitive non-toxigenic spores and the neutralization of antibiotics at the microbiota level. Future successful treatments will likely involve a combination of therapies to provide the most effective and robust approach to C. difficile management.

01 Jan 2022·ImmunotherapeuticsQ3 · BIOLOGY

Antivenom: An immunotherapy for the treatment of snakebite envenoming in sub-Saharan Africa

Q3 · BIOLOGY

Article

Author: Mender, Mender M ; Young, Mark ; Berry, Colin ; Bolton, Fiona

Snakebite envenoming (SBE) leads to significant morbidity and mortality, resulting in over 90,000 deaths and approximately 400,000 amputations annually. In sub-Saharan Africa (SSA) alone, SBE accounts for over 30,000 deaths per annum. Since 2017, SBE has been classified as a priority Neglected Tropical Disease (NTD) by the World Health Organisation (WHO). The major species responsible for mortality from SBE within SSA are from the Bitis, Dendroaspis, Echis and Naja genera. Pharmacologically active toxins such as metalloproteinases, serine proteinases, 3-finger toxins, kunitz-type toxins, and phospholipase A₂s are the primary snake venom components. These toxins induce cytotoxicity, coagulopathy, hemorrhage, and neurotoxicity in envenomed victims. Antivenom is currently the only available venom-specific treatment for SBE and contains purified equine or ovine polyclonal antibodies, collected from donor animals repeatedly immunized with low doses of adjuvanted venom. The resulting plasma or serum contains a high titre of specific antibodies, which can then be collected and stored until required. The purified antibodies are either whole IgG, monovalent fragment antibody (Fab) or divalent fragment antibody F(ab')₂. Despite pharmacokinetic and pharmacodynamic differences, all three are effective in the treatment of SBE. No antivenom is without adverse reactions but, the level of their impact and severity varies from benign early adverse reactions to the rarely occurring fatal anaphylactic shock. However, the major side effects are largely reversible with immediate administration of adrenaline and corticosteroids. There are 16 different antivenoms marketed within SSA, but the efficacy and safety profiles are only published for less than 50% of these products.

01 Jan 2022·Immunotherapeutics

CoVaccine HT™ adjuvant is superior to Freund's in eliciting ovine polyclonal antibodies against human tumor necrosis factor-alpha

Article

Author: Griffiths, Owen R ; Landon, John ; James, Philip E ; Adams, Rachel A ; Morris, R Keith

INTRODUCTIONPassive immunotherapy using polyclonal antibodies plays an important role in preventing and treating antigenic and pathogenic diseases. Polyclonal antibodies are used for therapeutic, diagnostic and investigational purposes, with adjuvants employed to enhance the immune response against proteins that are poorly antigenic or self-antigens. This study aimed to optimize current immunization methods by evaluating the novel adjuvant CoVaccine HT™ against the established Freund's at producing ovine polyclonal antibodies against pro-inflammatory cytokine human recombinant tumor necrosis factor alpha (TNF-α).METHODSCastrated male Aberfield cross sheep were immunized with TNF-α in CoVaccine HT™ or Freund's adjuvant. The binding titer of antibodies for TNF-α and neutralization titer were determined in vitro, as well as the strength of antibody binding by a simple small scale affinity chromatography elution experiment. Animal welfare was monitored through inspection of immunization site reactions at regular time points and graded according to reaction size. The second part of the study looked at re-immunization using Freund's adjuvant alone every 4- or 8-weeks.RESULTSFreund's generated significantly higher antibody binding titers than CoVaccine HT™ but were less effective at neutralizing TNF-alpha which is a better indicator of functional potency. CoVaccine HT™ also caused fewer immunization site reactions, while no statistical difference was observed in the binding strength of antibodies. Re-immunization every 4- and 8-weeks showed no statistical difference.CONCLUSIONThis study provides evidence that CoVaccine HT™ is superior to Freund's adjuvant for the production of antibodies to TNF-α, and supports the use of this alternative adjuvant for clinical and experimental use. The outcomes gained through this study are applicable to passive and active immunotherapy for the generation of polyclonal antibodies in human and veterinary medicine.

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100 Translational Medicine associated with MicroPharm Ltd.

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Pipeline

Pipeline Snapshot as of 22 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

VIPERFAV	Crotaline Snake Venom More	Approved
EchiTAbG	Crotaline Snake Venom More	Approved
BOTHROFAV	Crotaline Snake Venom More	Approved
Antivenom PolongaTAb (Protherics)	Snake Bites More	Discontinued
PolyCAb ( toxB )	Clostridium difficile infection More	Pending