LPS as a control for better treatment in animal health
Animal health has been a growing field of studies and research these past years. Increasing production yields could be challenging because there are multiple factors that come into the equation of animal farming. From feeding to immunization, from preventive measures to therapeutics, there is a common danger to animal health: pathogens, toxins and among them, LipoPolySaccharides (LPS) from bacteria.
Bacterial antigen screening
Bacterial screening is the first important step, for selecting the right antigens that will be included in your vaccine. LPS-BIOSCIENCES can analyze the LPS structures from several bacterial strains in order to select the strains showing the epitopes you need for your vaccines.
Bacterial culture conditions could also influence antigen structure and activity. Thus, changing the culture medium or scaling up biomass production come together with the study of antigen structural properties. It is very important that you check the structures of LPS antigens when you switch from R&D small scale fermentation to GMP large scale conditions.
When the procedure for vaccine production is modified, the final product needs to be validated by regulatory authorities. This validation may require analysis of bacterial antigen in terms of its structure and activity.
Bacterial antigen preparation for vaccine production
Bacterial antigen purification requirements are crucial for all vaccine developers.
Indeed, having the right antigenic structure, and purity, is needed to induce protection against the right serovar. There are many methods described in the literature, for Lipopolysaccharide extraction, however classical methods like the hot phenol/water extraction do not meet with the requirement of preserving the structure and the diversity of bacterial antigens. Using Phenol / water extraction may harm LPS decorations and modify their structure.
Phenol has been used for ages to extract LPS or separate endotoxins from polysaccharide antigen but the results are mixed in terms of effectiveness. You need several extraction washes to get rid of endotoxins and sometimes it does not work because of specific LPS structures.
Using innovative and more gentle eco-friendly solvents, and avoiding hazardous ones such as phenols or chloroform, will also become mandatory to manufacture bacterial antigen molecules in the near future. How big would be the impact to adapt a regulatory-certified production method to new regulations?
This would not only save a lot on regulatory hurdles and financial stress, but also keep operators on the production lines safe as well as avoid toxic effluents to preserve the environment.
Development of multivalent veterinary vaccines
Similarly, to human health, the best protection against pathogens is vaccination. Despite easier regulations, it is still a requirement to study the impact of vaccines on animals.
Among the vaccine development steps, the most important part would be the selection of the best bacterial antigen. It will directly impact the vaccine’s safety and efficacy. It will also directly impact the ability to develop multivalent vaccines candidates to provide a broad range of immunization. The canine vaccine against leptospirosis provides a good example of a successful multivalent vaccine since it provides an effective protection against multiple Leptospira serovars.
Another important aspect would be to set up the right production process to get high purity antigen. To optimize the production yield, many factors come into play, from the strain selection to the culture conditions and DownStream Process.
Impact of feeding on LPS expression by the gut microbiota
The one and foremost need in raising animals is food. Feeding is an important process as it has a direct impact on the production yields of farms. Research is developing in this area to control the feed composition and optimize animal growth. Both research axes study the feed impact on the gut microbiota and nutrient intake. Indeed, knowing that bacterial endotoxins in the gut flora can impact nutrients absorption and increase pathogenic cases with bowel inflammation: LPS in gut microbiota deserves to be carefully addressed.
Indeed, microbiota disbalance can lead to lipopolysaccharide translocation in blood, resulting in inflammation, and septic shock in the worst cases. Even lethal situations for domesticated animals can occur in case of contamination with Shiga toxin-producing E. coli for example.
In order to deal with it, rather than analyzing random samples from the flock, it is easier to control animal food. Controlling what animals ingest is also a regulatory requirement; avoiding tainted food by endotoxins from Salmonella, E. coli or Enterobacteria is the basis of a healthy farm, but it is only one approach. A second way that developed in recent years is to control the cattle gut microbiota through nutraceutical, functional food. In this case, there is an active intention to develop certain predetermined strains of bacteria in the gut through the food.
Impact of antimicrobial compound on Lipopolysaccharides structure
While effective, vaccination does not cover all types of infectious diseases. Reactive measures should be taken once in a while, and antibiotics are the most common and widely spread solutions to keep livestock healthy.
Antibiotics do wonders overall, but unfortunately, bacterial resistances appear sometimes. Resistances usually appear when prescriptions are not followed carefully, and most of the time it is related to an excessive use of antibiotics. The main risk in such cases is zoonosis, i.e. the transmission of an animal disease to Man.
Studying lipopolysaccharides’ structures could provide a great help to prevent such risks:
- by understanding the role of LPSs in pathogenicity
- by studying the impact of LPS modifications in bacterial membranes and their relationship to the newly acquired resistance
Ultimately, the identification of such a connection between LPS structure and bacterial resistance and pathogenicity can provide an interesting solution to screen new drug candidates and develop therapeutic options.