Inactivated killed vaccines
In addition to the Sabin attenuated poliovirus vaccine, an inactivated vaccine (the Salk vaccine) pioneered at the same time is still used in many countries today. Inactivation of the Salk vaccine typifies the approach to producing killed vaccines. High titers of wild-type virus are grown in cell culture and inactivated by the use of chemicals such as b-propiolactone or formaldehyde. The Salk vaccine is administered subcutaneously or intradermally to stimulate an immune response. With no subsequent virus replication (as seen with live vaccines) the immune response follows that of a primary response to an inert antigen but the necessary high levels of antibody are therefore stimulated only by multiple injections.
Killed vaccines have the advantage that they show no reversion to virulence, and are also stable and easy to store, often not requiring refrigeration. They can be administered to immune-suppressed patients and are usually not affected by interference from other pathogens, which is important in many developed countries. Killed vaccines, however, can be expensive and difficult to inactivate (no single infectious particle can remain in the preparation) and considered dangerous to manufacture (before inactivation). They do not stimulate the full scope of the immune system and require multiple (booster) doses. The recently derived hepatitis A vaccine is an inactivated vaccine, primarily pro- duced because it was technically impossible to develop an attenuated hepatitis A virus capable of replication within the liver without disease. It is considered that the use of killed vaccines alone, which often allow some wild-type virus replication at local sites (e.g. poliovirus), will not be sufficient to totally eradicate viruses from the world.