Immunomodulatory Agents
Natural host defence peptides possess both anti-biofilm and immunomodulatory activities. The immunomodulatory functions of this class of molecule include the ability to suppress certain pro-inflammatory pathways and up-regulate anti-inflammatory mechanisms while maintaining efficient innate immune responses. Through extensive peptide design studies, we have developed a set of synthetic innate defence regulator (IDR) peptides, thematically based on natural host defence peptides, which have enhanced immunomodulatory profiles compared to their natural counterparts. ABT Immunomodulatory Peptides have been particularly designed to enhance the anti-inflammatory activity of synthetic IDR peptides to mitigate the damaging effects of excessive inflammation that can accompany infections or other immune disorders.
Exploiting the immunomodulatory functions of these IDR peptides represents a new therapeutic approach to treat infections and inflammatory disorders. The key advantage of developing IDR peptides to treat infections is that they do not exert selective pressure on the organism to develop resistance as their effects are primarily directed at the host rather than the pathogen and they work by selectively enhancing host immune mechanisms. It is extremely likely that such a treatment would be developed to treat infections as an adjunctive therapy in combination with conventional antibiotics. Moreover, the ability of IDR peptides to carry noticeable antimicrobial effects, makes them useful as immune modulators for infectious diseases, as well as anti-inflammatories for acute and chronic inflammatory disorders (e.g. asthma), and suppressors of pathogen-induced inflammation.
ABT peptide dampened the inflammatory response in a sterile model of inflammation in mice. Inflammation in the mouse ears was induced by application of phorbol myristate acetate and treated topically with an anti-inflammatory ABT peptide, IDR-1002. In vivo imaging was performed 6 hours post treatment. To visualize reactive oxygen and reactive nitrogen species production the luminescent probe, L-012, was employed and mice were imaged using an IVIS Spectrum (A). To detect neutrophil recruitment, a neutrophil-specific probe, NIR Fluorescent Imaging Agent, was used and mice were again imaged using an IVIS Spectrum (B). In both cases, peptide treatment reduced the fluorescent signal arising from the inflammation specific chemical probes, reflecting their strong anti-inflammatory activity. Fig.: Mechanisms of the Innate Defense Regulator Peptide-1002 Anti-Inflammatory Activity in a Sterile Inflammation Mouse Model. J Immunol. doi: 10.4049/jimmunol.1700985.
ABT Immunomodualtory Peptide, IDR-1018, enhances wound healing in an infected porcine model of skin wound infection. Fig.: Innate defense regulator peptide 1018 in wound healing and wound infection. PLoS ONE. doi: 10.1371/journal.pone.0039373.
Vaccine Adjuvants
Vaccinations have proven to be the single most effective tool to manage and prevent infectious diseases in humans. Adjuvants are critical components of vaccines and the key to a single shot vaccination strategy. Despite the extensive worldwide success of vaccines, new vaccine development has been limited by inadequate protective immune responses and the need for multiple dosing to raise a protective response. Our ABT Immunomodulatory Peptide technology can be incorporated into vaccines as adjuvants and address these issues by enhancing the body’s response to a vaccine and ensuring an appropriate immune response to maximize the immune protection gained through vaccination. The key advantages of our peptide adjuvant formulations are their ability to induce a high antibody titer and generate protective immune responses against pertussis, RSV, Chlamydia, Flu as well as other model antigens. Moreover, they have been shown to enable the creation of single dose vaccines (e.g. pertussis) which eliminates the need for multiple dosing, likely improving vaccine uptake in the population.
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