Immunology and vaccinationInnovating for vaccination
Seppic has been a player in vaccine adjuvants for more than 40 years in animal health, and 25 years in human health. In human health, our adjuvants are used in many vaccine studies and support vaccine research. In animal health, our immunology laboratory, integrated since 1992 within the research laboratories of the Ecole Vétérinaire Nationale d'Alfort (EnvA, France), guarantees the efficacy and good tolerance of our vaccine adjuvants. It has strong collaborative partnerships with institutes and societies specialized in veterinary medicine, in France and around the world.
Developing an immune response
Most vaccines are so-called "prophylactics", i.e. they help prevent infectious diseases in humans and animals. The principle is based on administering an active principle – a fragment or whole infectious agent, called an antigen – to develop a specific immune response without causing disease. The subsequent immune response enables the individual to protect himself against a natural infection.
So-called "therapeutic" vaccines are used to fight disease that has already occurred in an individual. They are designed to specifically stimulate the immune system, for example to reject cancer cells, and are notably used in oncology as part of immunotherapy.
Mechanism of action of vaccine adjuvants
In vaccination, adjuvants are substances that increase the intensity of the immune response after co-administration with the antigen.
Injection of the antigen-adjuvant pair causes a massive influx of immune cells and mediators at the site of administration (injection site). For some adjuvants such as emulsions, a desposit effect occurs. The adjuvant allows the protection and progressive diffusion of the antigen to ensure an effective and prolonged stimulation of the immune system.
Together, these elements facilitate the capture of the antigen by specialized immune cells, known as antigen presenting cells (APCs). These cells are at the interface between two immune systems: innate (fast and non-specific) and adaptive (slow and specific).
Innate immunity plays a key role – not only chronologically, but also functionally – through its influence on the development of the adaptive response, as its many effectors play a central role in the early stages of the immune response. Adjuvants amplify the danger signal triggered by the administration of the antigen, and thus stimulate this phase of immunity. Granulocytes and monocytes are part of the cellular arsenal involved in this primary response in order to fight or contain an infection, until a specific and more effective response takes place. Phage cells, such as dendritic cells, have the ability to internalize and eliminate antigen.
The relay is then switched to adaptive immunity, in which the dendritic cells exert their activity as antigen-presenting cells, and migrate from the injection site to effector organs of the immune response to be brought into contact with T cells and effectively present the antigen to them. Only T cells capable of recognizing the antigen activate, and multiply to elicit a response specifically targeting the antigen. This phenomenon also involves different molecules called cytokines, which are necessary for communication between the cells involved.
The nature of the antigen and adjuvant influence the type of response induced. Two complementary immune response pathways, with an associated cytokine signature, are the consequence of this activation: the Th1 pathway (T helper) called cellular immunity, and the Th2 pathway called humoral immunity. Cellular immunity involves phage cells and cytotoxic cells that promote the elimination of pathogens that propagate in the body's cells, such as viruses for example. Humoral immunity involves the production of antibodies able to stop the migration and proliferation of extracellular pathogens. The presence of an adjuvant can direct the immune system to fight a pathogen more effectively by favouring one pathway or the other.
The main property of adaptive immunity is generation of immune memory, which is the basis for vaccination to effectively fight the infectious agent from which the vaccine antigen is derived.
The case of immunotherapy
In immunotherapy, particularly in oncology, the strategy is to help the immune system recognize and destroy cancer cells. These cells are distinguished from healthy cells by the expression on their surface of specific markers that can be a target. These markers escape the immune system’s scrutiny, because the cells are capable of producing inhibitors that inactivate the body's defences.
The therapeutic approach therefore aims to awaken the immune system so that it can eliminate the cancer cells. This is the immune response’s mechanism of action with vaccination. In the context of a therapeutic vaccine, the cell type response is preferred for destroying tumour cells.
New routes of administration
The new generations of vaccines offer needle-free solutions that are administered through the mucous membranes of the body, such as those found in the nose, mouth, or even eyes. Mucous membranes are the main route of entry for pathogens during a natural infection. This compartment is very rich in sentinel immune cells to fight infections. Mucous membranes are therefore a strategic point to target for vaccine efficacy. In animal health, this mode of administration is particularly suitable for mass vaccination, especially in chicken or fish farms.
The skin is also an alternative route of administration increasingly used in non-invasive vaccination. As with mucous membranes, the skin is provided with a large quantity of immunocompetent cells. The use of devices such as patches or injection guns allow different layers of the skin to be targeted, which is referred to as epidermal, transdermal or transcutaneous vaccination.
Overall, these new, simpler-to-use vaccines can provide local, mucosal and systemic protection.
Seppic is developing a wide range of vaccine adjuvants covering the diversity of needs, including those specific to this new route of administration. One challenge for our immunology laboratory is to explore and characterize innovative adjuvants for these new applications.
The Immunology Laboratory
Thanks to state-of-the-art equipment, the immunology laboratory uses various techniques to study the performance of adjuvant formulas and analyze the different components of the immune response. The characterization of the immune response induced by adjuvants is an essential part of meeting our customers’ needs. This takes into account the efficacy of our products, but also their safety. The techniques most commonly used in the laboratory allow us to have a precise vision of each major step in the immune response:
- ELISA (Enzyme Linked Immuno Sorbant Assay) for the detection and dosage of antibodies or soluble molecules (cytokines) of the immune system from serum,
- ELISpot for the identification of a target cytokine from cultured cells,
- Flow cytometry for information on cell populations such as lymphocytes: their identification, the evaluation of their biological activity, or their level of activation,
- Immunohistochemistry to assess inflammatory reactions at the injection site of vaccines,
- Molecular biology tools to characterize activation pathways through gene expression, in particular to understand the mechanisms of action involved in innate immunity.