Vaccines are harmless agents, perceived as enemies. They are molecules, usually but not necessarily proteins, that elicit an immune response, thereby providing protective immunity against a potential pathogen. While the pathogen can be a bacterium or even a eukaryotic protozoan, most successful vaccines have been raised against viruses and here we shall deal mostly with anti-viral vaccines.

Immunity to a virus normally depends on the development of an immune response to antigens on the surface of a virally infected cell or on the surface of the virus particle itself. Immune responses to internal antigens usually play little role in immunity. Thus, in influenza pandemics, a novel surface glycoprotein acquired as a result of antigenic shift characterizes the new virus strain against which the population has little or no immunity. This new strain of influenza virus may, nevertheless, contain internal proteins that have been in previous influenza strains. Surface glycoproteins are often referred to as protective antigens. To make a successful vaccine against a virus,  the nature of these surface antigens must  be known unless the empirical approach of yesteryear is to be followed. It should be noted, however, that a virally-infected cell displays fragments of internal virus antigens on its surface and these can elicit a cytotoxic T cell response that acts against the infected cell.

There may be more than one surface glycoprotein on a virus and one of these may be more important in the protective immune response than the others; this antigen must be identified for a logical vaccine that blocks infectivity. For example, influenza virus has a neuraminidase and a hemagglutinin on the surface of the virus particle.  It is the hemagglutinin that provokes neutralizing immunity because it is the protein that attaches the virus to a cell surface receptor and the neutralizing antibody interferes with virus binding to the cell.

In addition to blocking cell to virus attachment, other factors can be important in the neutralization of viruses; for example, complement can lyse enveloped virions after opsonization by anti-viral antibodies.