Another common approach in vaccine production is inacti-vation of the pathogen by heat or by chemical means so that it is no longer capable of replication in the host. It is critically important to maintain the structure of epitopes on surface antigens during inactivation. Heat inactivation is generally unsatisfactory because it causes extensive denaturation of proteins; thus, any epitopes that depend on higher orders of protein structure are likely to be altered significantly. Chemical inactivation with formaldehyde or various alkylating agents has been successful. The Salk polio vaccine is produced by formaldehyde inactivation.
Attenuated vaccines generally require only one dose to induce long-lasting immunity. Killed vaccines, on the other hand, often require repeated boosters to maintain the immune status of the host. In addition, killed vaccines induce a predominantly humoral antibody response; they are less effective than attenuated vaccines in inducing
Reported polio cases
Progress toward the worldwide eradication of polio. Comparison of infection numbers for 1988 with those for 1998 show considerable progress in most parts of the world. Some experts question whether the use of live attenuated oral polio vaccine will cause reversion to pathogenic forms at a rate sufficiently high to prevent total eradication of this once prevalent crippling disease. [Data from WHO.]
Even though they contain killed pathogens, inactivated whole-organism vaccines are still associated with certain risks. A serious complication with the first Salk vaccines arose when formaldehyde failed to kill all the virus in two vaccine lots, which caused paralytic polio in a high percentage of recipients.
Risk of complications from natural measles infection compared with known risks of vaccination with a live attenuated virus in immunocompetent individuals
Risk after natural disease*
Risk after vaccination
Post-infectious encephalomyelitis SSPE
0.1-1 per 1000 (up to 5-15% in developing countries)
1 per 1,000,000 0
1 per 30,000s 0
*Risk after natural measles are calculated in terms of events per number of cases. TRisks after vaccination are calculated in terms of events per number of doses.
^Although there have been several reports of thrombocytopenia occurring after measles including bleeding, the risk has not been properly quantified. §This risk has been reported after MMR vaccination and cannot only be attributed to the measles component. MMR = measles, mumps, and rubella. SSPE = subacute sclerosing panencephalitis.
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