An adjuvant is a substance that enhances the immune system’s response to the presence of an antigen. They are commonly used to improve the effectiveness of a vaccine. Generally, they are injected alongside an antigen to help the immune system generate antibodies that fight the antigen.
Image Credit: gopixa / Shutterstock.com
While they are commonplace in the development of vaccines, the mechanisms underlying how exactly they influence the immune system is still not completely understood. However, recent studies have helped to uncover key information.
The use of adjuvants in vaccines
The purpose of adding adjuvants into vaccines is to boost the immune system response and to allow for fewer doses or lesser quantities of the vaccine to be administered. Aluminum, one of the most commonly used adjuvants, was first discovered to have adjuvant properties back in 1926.
Since then numerous vaccines, such as hepatitis A, hepatitis B, diphtheria-tetanus, Haemophilus influenza type b, and pneumococcal vaccines have been developed with the use of aluminum adjuvants. Today, a number of different kinds of adjuvants have been discovered and successfully used to develop new vaccines. We discuss these below.
Scientists theorize that adjuvants may act through a number of mechanisms to have the impact of enhancing the immune system response. Studies have revealed that adjuvants are likely to influence mechanisms such as the induction of cytokines and chemokines, the formation of depot, the promotion of antigen transportation to drain the lymph nodes, and the enhancement of antigen uptake and presentation.
Research has revealed that adjuvants are likely generating immuno-competent environments at the location of the vaccine injection through the activation of an innate immune response. It is this innate response, the type that is activated, which governs how the quality of the adaptive immune responses are altered.
How do adjuvants work?
When adjuvants are added into a vaccine they work in four distinct ways to boost the immune response. The first of these pathways is the activation of antigen-presenting cells to signal to the immune system’s T cells that foreign substances have infiltrated.
To do this adjuvants boost the activation of antigen-presenting cells, cells of the immune system that encompass foreign substances and break them up, presenting the resulting particles to the immune system’s T cells. This activates the T cells, which has the impact of activating the antibody-producing B cells.
The second way that adjuvants work is by activating T cells indirectly by discharging phagosomes that attach themselves to the T cells. Following this binding, the T cells are induced to release cytokines that switch on the antibody-producing B cells.
The next process involves the targeting of antigens at specific locations. The location where an adjuvant is injected can induce immune system activity localized to that specific area. This activation incites T cells to travel through the bloodstream to that specific location.
Finally, adjuvants can induce the slow release of an antigen. The depot effect refers to the process by which adjuvants can regulate the rate of antigen release into the bloodstream. To achieve this, the adjuvant is enclosed within a polymer along with an antigen. This has the impact of reducing the rate at which both the chemicals and antigens are released into the tissue and bloodstream.
Types of adjuvant
Since the discovery of aluminum’s function of an adjuvant back in 1926, many more substances have been recognized as adjuvants and used to create a variety of vaccines.
To begin with, aluminum, as discussed, is a common type of adjuvant. These are often added into vaccines in the form of mineral salts. It is particularly competent at activating the Th2 immune response, which is characterized by the release of Interleukin 5 and is often associated with the removal of parasites.
However, it is not as effective at activating the Th1 response, which causes B cells to attach themselves to antigens to allow other immune cells to identify and kill whatever substance is clinging to the antibody.
Oil emulsions are another type of widely used adjuvant. These mixtures of oil and water have proven their effectiveness at generating strong immune responses. Like aluminum, these substances are excellent at inducing the Th2 immune response. Also, they are good at creating a slow-release effect.
Microbial substances, such as sugars from the cell walls of microbes, can be used to induce intense immune reactions due to the body’s natural response against microbes.
Saponins are a group of chemical compounds that exist in abundance in numerous species of plants. These steroid molecules with attached sugar chains can also trigger an intense immune response at a low dose.
Cytokines are a group of peptides that play a vital role in cell signaling. Interferons and interleukins are specific types of cytokines that are naturally released by cells in the immune system in order to generate mutual activations. Certain types of these cytokines can be used to evoke specific immune cell responses.
Finally, scientists have successfully established various synthetic adjuvants. Specifically, molecules have been designed that activate the immune cell’s PRR and TLR receptors, having the impact of switching on genes that indicate the presence of an infection to neighboring cells.
Scientists will continue to investigate the mechanisms responsible for how adjuvants influence the immune response. Growth in the understanding of these processes will help to develop new and safe vaccines for a wider range of afflictions.
Awate, S., Babiuk, L. and Mutwiri, G. (2013). Mechanisms of Action of Adjuvants. Frontiers in Immunology, 4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655441/#!po=46.9697
Nash, A., Dalziel, R. and Fitzgerald, J. (2015). Vaccines and How They Work. Mims' Pathogenesis of Infectious Disease, pp.291-303. https://www.sciencedirect.com/science/article/pii/B9780123971883000123
Warren, H. and Leclerc, C. (1998). Adjuvants. Encyclopedia of Immunology, pp.36-39. https://www.sciencedirect.com/science/article/pii/B0122267656000104