Roadmap for Immunomodulators

What are we trying to achieve and why? What is the problem we are trying to solve?

Specific resistance of animals:

• The use of bacteria that stimulate/reprogram the immune response; Probiotics; Prebiotics that stimulate growth of immunostimulatory bacteria; AMP; Phytochemicals; Other immunogenic compounds (e.g. nutraceuticals, biomolecules); Develop C-terminal VH region of camelid heavy chain antibodies (VHH) that target pattern recognition receptors;
• Passive immunisation strategies; Antibodies derived from blood used as additives/for nutrition; Microbiota modification.

What are the scientific and technological challenges (knowledge gaps needing to be addressed)?

Consistent research methodologies to enable evaluation of efficacy and comparison between groups and technologies.
(Animal factors: different batches of animals give different results – different models for species?/environment).
Consistent production of the immunomodulator.
Interaction among different immunomodulators (investigate mode of actions)
Interaction with nutrients.
Ensuring efficacy (at least up to 30% as compared to antibiotics).
Robust response without over stimulation of the immune system.
Reducing unwanted inflammation (in mucosal surfaces).
Consistent research methodologies to enable evaluation of efficacy and comparison between groups and technologies (e.g., what defines ‘resilience’).
Identification of host factors that determine tolerance (proof of cause-effect relationship).
Pointing out the critically important elements of nutrition and the way feeding is performed that prevent diseases, and if the elements differ in relation to the cause of the disease.
Understanding reasons behind failure of immunomodulators that were brought to the market earlier.
Routes of administration (oral vs parenteral and impact on other compartments).
Frequency of administration.
Dosage.
Resistance to the technological process when delivered by feed (e.g. temperature when preparing feed).
Type of formulation and shelf-life of the product.
Genetic and age of the host.
Palatability of the formulation.
Storage requirements in different environments.

What approaches could/should be taken to address the research question?

Field studies to establish the efficacy and safety of:

• Bacteria that stimulate/reprogram the immune response.
• Probiotic.
• Prebiotics that stimulate growth of immunostimulatory bacteria.
• AMP.
• Phytochemicals
• Nutrition.
• Other immunogenic compounds (e.g., nutraceuticals, biomolecules).
• C-terminal VH region of camelid heavy chain antibodies (VHH) that target pattern recognition receptors.

Passive immunisation strategies.
Microbiota modification.
Antibodies derived from blood used as additives/for nutrition
Investigate cross immunomodulations among different compartments)

What else needs to be done before we can solve this need?

Establishing mode of action of the various candidates
Investigating early life programming of the immune system from a Th2 to a Th1 response.
Investigating innate defence pathways (e.g., interferons) and how they are impacted by specific agents.
Studying the impact of probiotics on the immune response.
Investigating AMP that modulate immune responses as well as attack bacteria.
Investigating nutrition requirements to maintain optimal immune response.
Using cytokines.
Using phytochemicals.
Better understanding interaction between immune responses and inflammation.
Investigating competitive exclusion.
Using enzymes able to break down the toxins produced from pathogens.
Studying innate immune memory.
Investigating epithelial cells metabolism and proliferation.
Investigating down-regulation of receptors for pathogens in animals.
Understand the metabolic cost of this approach.
Investigating impact of live vaccines (competitive colonisation)
Evaluating nutritional compounds (e.g., metals, vitamins)

Existing knowledge including successes and failures