5.2 Antigens and immunogens
In Section 3 we highlighted the need for vaccines to contain pathogen-specific critical antigens, which provoke a protective immune response. Clearly, a vaccine that did not contain critical antigens would be ineffective, but we must now extend the discussion to include other influences on vaccine efficacy. We noted above that pathogens can have antigens that do not induce a protective immune response and that (in most people) antigens in foods do not elicit immunity at all. This introduces an important concept in immunology. It is necessary to distinguish between antigenicity, the ability of a molecule to be recognised as non-self by the cells of the immune system – and immunogenicity, the ability of that antigen to induce an immune response. Immunogenicity is not a fixed property: whether a particular antigen behaves as an immunogen is highly contingent on a number of interacting factors, including:
the route by which it is delivered (e.g. orally; injected into the skin; inhaled intranasally); and the quantity of antigen in the ‘dose’;
the genetic make-up of the immunised person and how this affects the ability to make an immune response to a particular antigen;
the molecular structure of the antigen (e.g. carbohydrate, protein, lipid);
the presence of other molecules that enhance immune responsiveness.
How could the route of administration influence the kind of immune response that develops against the antigens in a vaccine?
Different parts of the body have different antigen-presenting cells, and this determines how an antigen is presented and what kinds of T cells are stimulated.
Antigen presentation partly determines whether a T helper-1 (Th1) or a T helper-2 (Th2) type of response is favoured. Antigens presented to Th1 cells initiate the sequence of events culminating in cell-mediated immune responses; antigens presented to Th2 cells initiate antibody-mediated responses. In practice, both types of response can occur simultaneously, but the route of administration can favour one or the other. It can also influence the class of antibodies that appear: antigens presented in the gut will tend to induce IgA production, since large numbers of IgA-producing B cells are located there; by contrast, antigens injected into the skin will usually be transported to local lymph nodes, where IgG- and IgM-producing B cells predominate.
Explain how the genetic make-up of an individual can affect antigen presentation and why this has an influence on whether a vaccine is immunogenic.
Antigen-presenting cells take up the vaccine antigens, process them internally and present peptide fragments in the cleft of their own surface MHC class II molecules. The genes encoding the MHC molecules vary between individuals, producing variations in which peptides can be presented to other cells in the immune system. Different individuals will present some protein antigens more efficiently than others. Inefficient antigen-presentation means that these antigens may be less immunogenic in that individual, even though they may provoke a strongly protective immune response in individuals with a different set of MHC class II molecules.
What implication does this have for vaccine design?
The variation in MHC molecules in a population means that the antigens used in vaccines must be presented efficiently in genetically different individuals.
In addition to the MHC, several other gene loci have been identified that affect the ability to generate a protective immune response; these include genes that affect antigen processing, as well as those involved in cytokine production and cell/cell interactions.
The molecular structure of an antigen can also affect whether it is immunogenic and the type of immune response it generates. Carbohydrates, lipids and glycolipid antigens are processed differently to protein antigens and they are not presented by conventional MHC molecules; for example, glycolipids are presented by a surface molecule designated CD1. Carbohydrates do not generally induce antibody class-switching, so they do not induce the production of high affinity IgG antibodies. We shall not go further into the details of how non-protein antigens are handled by the immune system, but you should note that it is essential that vaccines induce a strong, effective and long-lasting immune response to certain carbohydrates and glycolipids.
Can you explain why?
The surface of many bacteria consists of carbohydrates and glycolipids, and an effective antibody response against them is highly desirable.
The immunogenicity of pathogen antigens is thus essential to vaccine design, but this is often hard to achieve; for example, some critical antigens are not sufficiently immunogenic in a wide enough range of individuals. However, various other components of the vaccine preparation can be added to enhance the immune response. Such components are called adjuvants.