ment in 1949 of the tissue culture technique for supporting virus growth made development of a vaccine possible (Enders et al., 1949). It was for these findings that J.F. Enders, F.C. Robbins, and T.H. Weller received the Nobel Prize in 1954. This development was followed by efforts to generate sufficient quantities of the virus to inactivate it and use it as an inert antigen. An alternative approach was to attenuate the wild-type virus and render it safe as a replicating antigen. Both were successful and today there are two forms of the vaccine: the inactivated polio vaccine (IPV), which is administered by the parenteral route, and the live attenuated vaccine, which is administered orally and hence is known as the oral polio vaccine (OPV).

IPV was developed in 1953 by Jonas Salk (Salk, 1953; Salk et al., 1953); OPV was developed by Koprowski and colleagues (1952), who were the first to use it, and Albert Sabin (1956). An enhanced-potency IPV was developed in the late 1970s and is used today. Currently, IPV and the Sabin strains of OPV are available for use in the United States; however, OPV is the vaccine recommended for general use and is the most prevalent (American Academy of Pediatrics, Committee on Infectious Diseases, 1991).

Shortly after the licensure of IPV in 1955, the vaccine manufactured by Cutter was found to cause paralytic disease. It contained residual infectious virus. The reason was traced to the method of inactivation. At that time the dynamics of the inactivation process were not fully understood, and the U.S. government's requirements for vaccine production were ambiguous. All of these problems have since been corrected.

The first OPV was licensed in 1960 after an extensive trial in the former Soviet Union (Benison, 1982). By then, over 100 million people in the former Soviet Union and Eastern Bloc countries—except Poland—had received the Sabin vaccine (LaForce, 1990). Trials of OPV in the United States followed, and monovalent OPVs were quickly licensed. The trivalent OPV used today was licensed in 1963. In the 1962 recommendations of the U.S. Public Health Service, no preference for one or the other form of the vaccine was expressed (U.S. Public Health Service, 1962), but in 1964 the Committee on Infectious Diseases of the American Academy of Pediatrics recommended the use of OPV.

Polio has been eliminated as an endemic disease in the United States and many developing countries. Outbreaks have occasionally occurred in subsets of unvaccinated susceptible individuals. A persistent concern has been the possibility of the rare complication of paralytic poliomyelitis in vaccinees and their contacts, particularly those with impaired immunity. This is discussed in detail later in this chapter. Some countries, for example, Denmark, use a mixed schedule of IPV followed by OPV. Other nations, such as Finland and Holland, continue to rely on IPV. The debate over the relative efficacy of OPV versus that of IPV continues in the litera-



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