Immune training, a cornerstone of the post-antibiotic era

Dr. Alain Riggi, DVM, Global Species Manager & Dr. Julie Schulthess, Immunity R&D Manager

Poultry phileo

Robust immunity in poultry flocks is essential to reducing reliance on antibiotics. Phileo’s post-antibiotic program provides three innovative nutritional solutions to boost overall poultry health. Safglucan®, a key element of the post-antibiotic program and rich in 1.3/1.6 β-glucans, is a proven solution to induce immune training, and in combination with appropriate vaccination strategies, can help generate robust healthy birds, ensuring poultry producers can transition away from antibiotics with confidence.

Poultry producers worldwide are transitioning away from the use of antibiotics as growth promoters. Antibiotic growth promoters in feed have been banned in EU since 2016 and in China since 2020, the trends are as well as due to changing consumer preferences as demonstrated by antibiotic-free products gaining more and more market share in the US.

However, help is at hand. Nutritional strategies which boost a bird’s natural immunity in tandem with appropriate vaccination management strategies can enable poultry producers to transition away from antibiotic use while maintaining both flock health and output.


Advanced nutritional strategies to bolster post-antibiotic poultry management

Immune training in poultry is a potent strategy which can effectively reduce dependence upon antibiotics. To enable poultry producers to successfully phase out antibiotics while also maintaining poultry health and profit, Phileo has developed a comprehensive post-antibiotic program founded on three advanced nutritional solutions : Safglucan®, Safmannan®, and Selsaf® which contribute to the program’s four foundational program pillars. These start with effective farm management and biosecurity measures to minimise pathogen penetration and limit outbreaks, to high-quality nutrition for the promotion of healthy growth, to enhancing gut health for improved pathogen resistance and feed conversion rates, to stimulating the birds’ innate immune systems to resist infection, additionally bolstered by comprehensive vaccination strategies.


Vaccination programs – a mainstay of healthy flocks

Vaccination programs are an essential component of poultry production; however, vaccination implementation does not follow a one-size-fits-all approach. We detail the key steps to achieving a robust vaccination strategy, as provided by a poultry vaccination expert.

Vaccination programs can vary greatly, and depend upon bird type (broilers vs longer-lived layers), maternal antibody status, disease types prevalent in an area, endemic situations, etc. As such, general vaccination recommendations should only be used as a guideline and cannot replace expert advice from a qualified veterinarian. Vaccines are commonly provided via mass vaccination—often in ovo or by spraying—within a hatchery. More equipment is automated in a hatchery, temperature and humidity are easier to control, hatchery staff are often better trained in vaccination strategies than farm staff, and a greater number of hatchery-appropriate vaccines are becoming available, promoting favourable responses.

Reactions to vaccination can heavily influence production performance, thus their avoidance is a major concern in broiler farming. In the field, timing of respiratory vaccinations is critical, too close together, and the bird can have adverse vaccine reactions, therefore, an interval of fourteen days is advised.


Stronger immune systems to reduce antibiotic use

The use of correctly-applied appropriate vaccines within a well-balanced veterinary-validated vaccination program will only provide decent levels of protection when the bird’s immune system is in optimal condition. Consequently, a major pillar of Phileo’s post-antibiotic program is immune system enhancement to produce robust birds that require less antibiotic intervention.

Immunity is driven by both innate and adaptive complex whole-body immune systems. The innate response is the first line of defence against an invading organism and once triggered, quickly mobilises phagocytic cells (monocytes, macrophages, dendritic cells, and neutrophils), complement proteins, antibodies, and small chemical messenger molecules (cytokines and chemokines) to destroy the attacking pathogen. Dendritic cells then break the pathogen down into small protein portions (antigens), which can then activate the adaptive immune response. Although the adaptive immune response needs time to develop, it is capable of building antigen-specific defence memory. This enables future attacks by the same pathogen harbouring identical antigen signatures to be dealt with rapidly via the reactivation of the original defence mechanism. This forms the basis of vaccination programs, whereby non-infectious pathogen antigen particles are able to stimulate the immune response, engendering an efficient response to any future natural pathogenic challenge.

It has been recently demonstrated that immune memory is not only the province of the adaptive immune system, but also occurs via the innate immune system. Furthermore, β-glucan has been shown to enhance immune responses and promote trained immunity. While not all β-glucans can trigger trained immunity, specific β-glucans from yeast have been proven capable of doing so. Therefore, Phileo has developed Safglucan® to help train poultry immune systems (Figure 1). This purified yeast fraction has high concentrations of 1.3/1.6 β-glucans (≥50%), and is one of the most promising complementary tools in the animal preventive care arsenal. Boosting an animal’s natural immune defence reduces the need to rely on antibiotics. Safglucan® has been demonstrated to support quality animal production.


Safglucan® – proven to strengthen the immune system

Phileo immunologists have developed a reference in vitro model to induce trained immunity by phagocytes. This model has been applied in a recent in vitro trial, a phagocytic immune cell model was stimulated with lipopolysaccharide (LPS antigen, also known as endotoxin, present in the membrane of certain pathogenic bacteria) at two time points, whereas the second group of phagocytes was primed by treatment with Safglucan®, and then challenged with LPS (Figure 2). Samples taken at both treatment steps demonstrated that Safglucan® induced a strong immune response compared to control as seen by significant increases in inflammatory cytokines IL-6 and TNF-α, p<0.0001 and p<0.0001, respectively (Figure 3). In a similar second experiment, Safglucan® produced significantly superior immune responses as observed with IL-6 and TNF-α levels compared to two other commercially-available β-glucan products (Figure 4).

Safglucan® is also proven to stimulate improved vaccine responses through immune training. In an in vivo trial performed in Mexico in 2016, 64 male Ross 308 birds were inoculated against Newcastle disease with an inactivated La Sota ND vaccine at D12 and D24. The birds were then divided into two groups, and the second group was supplemented with 125 g/t Safglucan® whereas the other was fed a control diet. Vaccine responses were evaluated by ELISA serology to measure Newcastle disease antibody titres (Figure 5). Vaccinated birds supplemented with Safglucan® demonstrated significantly higher Newcastle disease antibody titres at D35 compared to control (p<0.0001). The results showed that Safglucan® secured an increase in anti ND virus specific antibodies in the serum of supplemented chicken as compared to their vaccinated, but none-supplemented, counterparts.


Enhancing immune responses to reduce antibiotic use

Safglucan® is a purified yeast fraction rich in 1.3/1.6 β-glucans produced through unique processes from a proprietary Saccharomyces cerevisiae strain. The specific structure of Safglucan® contributes to its ability to stimulate poultry immunity. β-glucan is one of the molecules which has been shown to be able to train the innate immune memory. Indeed, Dectin 1, the receptors on innate immune cells, and phagocytes, specifically recognise β-glucans 1.3 and 1.6. The interaction between Dectin 1 and β-1,3 and 1,6 glucans lead to an immune activation of the phagocytes, allowing them to produce cytokines. One of the direct results of this interaction is the induction of trained immunity or innate immune memory in these phagocytes. These trials demonstrate that when provided at the right moment and with the appropriate dose, Safglucan® has the capacity to potentiate innate immunity. Thus, a combination of a suitable vaccination program and efficient feed supplements such as Safglucan® to boost innate immunity, can help producers reduce their reliance on antibiotics. Phileo’s post-antibiotic program founded on three promising nutritional supplements, Safmannan®, Selsaf®, and Safglucan®, easily enables poultry producers to transition away from antibiotics.


Figure 1 – Trained immunity model demonstrating the improved effect with Safglucan® supplementation (adapted from Goodridge 2016 et al1and Netea 2017 et al.2)

Figure 2 – Experimental design of immune training in an in vitro phagocytic cell model.

Figure 3 – Priming a phagocytic cell model with Safglucan® generates a strong immune response upon a second challenge.

Figure 4 – Safglucan® generated superior immune responses in an in vitro cell model compared to two other commercially-available β-glucan products.

Figure 5 – Birds vaccinated against Newcastle virus and supplemented with Safglucan® demonstrated significantly higher Newcastle disease antibody titres at D35.

References : 

1 Goodridge et al., 2016. Nat Rev Immunol 16, 392–400.

2 Netea et al., 2017 Cell Host Microbe 21, 297–300.

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