3 Critical antigens and the immune response
3.1 How do vaccines work?
Before we consider vaccine design in more detail, it is necessary to point out that not all immune responses protect the host against the target pathogen. Consider antibody-mediated responses induced by a vaccine. Antigens that induce protective antibodies against pathogens (or their products) are known as critical antigens; so if vaccines are to elicit a protective or therapeutic antibody response they must contain pathogen-specific critical antigens.
The external coat of most viruses is relatively simple, since it contains a limited number of antigens, which can be targeted by the immune system. Polio virus has just three protein components exposed on the surface of its capsid. By contrast, bacteria are structurally more complex and generally induce antibodies against a variety of proteins. For example, purified protein derivative (PPD) is an antigenic preparation derived from mycobacteria, which contains up to 200 different antigens. Nevertheless, there are often a limited number of antigens which determine the pathogenicity of the bacteria. In extreme cases, such as tetanus, the toxin is the only relevant antigen that must be neutralised; the bacterium by itself is not invasive or particularly pathogenic, but the toxin is one of the most toxic substances known.
Explain how antibodies that bind to the critical antigens of a pathogen can protect the host from infection.
Antibodies are multi-purpose defensive molecules, whose functions include: preventing viruses from invading host cells by binding to their attachment sites; ‘labelling’ pathogens for destruction by cytotoxic cells and phagocytes; cross-linking pathogens into immobilised aggregates; directing the lytic complement pathway onto cellular pathogens; and recruiting other components of the immune response to fight an infection.
The pathogenicity of many bacteria depends on their ability to avoid phagocytosis by actively moving away from phagocytes, or by being encased in an anti-phagocytic capsule. Antibodies can overcome these defences. For example, by binding to critical antigens in the capsule they allow phagocytes to engage the bacteria (opsonisation). Antibodies to flagella and other surface components reduce bacterial motility. Antibodies against bacterial enzymes such as collagenases, which promote the spread of streptococci and staphylococci, can also reduce the ability of these bacteria to invade tissues locally.
The critical antigens in some vaccines also induce cell-mediated immune responses in the recipient, which are particularly important in attacking pathogens that replicate inside host cells, i.e. all viruses and some bacteria, including mycobacteria (which cause TB and leprosy), and certain protoctist parasites (e.g. Toxoplasma gondii; Plasmodium species).