Intradermal Versus Subcutaneous Immunization of Monkeys Against Poliomyelitis

Abstract

Early experiments of Flexner and Lewis (1), Levaditi and Landsteiner (2), and RSmer and Joseph (3) showed that monkeys once recovered from poliomyelitis are immune to subsequent intracerebral inoculations of poliomyelitis virus. This immunity was apparent no matter how slight had been the symptoms of the initial infection. The refractory state was of long duration and was absolute within the limit of infecting doses employed. These same workers noted that sera of convalescent monkeys, when mixed with poliomyelitis virus in vitro, rendered the material, otherwise infective, inactive when introduced intracerebrally in test animals.These observations became the basis for numerous efforts to immunize animals against experimental poliomyelitis. Flexner and Lewis (4) injected monkeys subcutaneously with living active virus, beginning with a dose of 0.05 cc. This amount was given daily for four days and the series Was repeated twice with a four day rest period between each individual set of injections. After the last interval the animals received on successive days 0.1, 0.5, and 1.0 cc. of virus, and after one month 5.0 cc. A week's rest period then followed, after which time the animals were tested intracerebrally with 2.0 cc. of fresh Berkefeld filtrate of poliomyelitis virus. Control monkeys which received 0.1 to 0.01 cc. of a similar filtrate intracerebrally developed typical poliomyelitis, whereas the vaccinated animals remained free from symptoms.Levaditi and Landsteiner (5) attempted to immunize monkeys by a single subcutaneous inoculation of 0.5 cc. of virus suspension previously heated to 50°C. for 30 minutes. They failed to produce any immunity by this treatment. In another experiment glycerinated virus was heated to 50°C. for 2 hours; this heated virus was still active in producing disease when inoculated intracerebrally, but did not infect when given daily in subcutaneous doses of 2 cc. each over a period of one month. Nine days after the last subcutaneous injection two treated monkeys were tested intracerebrally. One of these showed slight prodromal symptoms of 959 on

Cross-Reactive Antibody Responses against Nonpoliovirus Enteroviruses

“…While poliovirus serotypes are defined by neutralization assays, the lack of cross-neutralization is not absolute: individual serotypes may be incompletely neutralized by antibodies raised against the other two serotypes ( 28 ), suggesting that antibodies able to neutralize multiple strains of poliovirus can be identified. Results from studies done in the 1920s and 1930s by Stewart and Rhoads, Aycock, and Burnet and Macnamara in which monkeys were infected with either the 1909 “MA” isolate of poliovirus from a fatal case of poliomyelitis, the Vermont “Aycok” isolate from 1920, or the Australian “Victoria” virus identified in 1928 and challenged with infection by a heterologous isolate provide evidence for some cross-protection among serotypes ( 29 – 31 ). Additionally, monospecific polyclonal sera from seven monkeys, each immunized with an individual untyped viral isolate from patients during the 1949 poliomyelitis outbreak in Kansas City, were found to partially neutralize more than one prototype poliovirus ( 32 ).…”

Immunization Against Poliomyelitis

“…Stewart and Rhoads (61) 20 % suspension of virus (strain unspecified). One developed paralysis from the vaccine.…”

Experiments on Active Immunization Against Experimental Poliomyelitis

“…The results of many efforts to induce resistance in Macacus rhesus monkeys against experimental poliomyelitis by means of inoculations of virus in one form or another have been summarized by Stewart and R_hoads (1929) (1) and in the volume published by the Milbank International Committee (1932) (2). What may be derived from these experiments, beginning with the first, undertaken 25 years ago by Flexner and Lewis (3), is that "it is impossible to protect monkeys by the use of killed virus and second, that a definite though inconstant resistance to poliomyelitis can be brought about by the intradermal and subcutaneous introduction of the living virus" (1). The fact also emerges from the numerous trials hitherto reported that resistance is acquired by monkeys when a sufficient amount of active virus is given intra-or subcutaneously in one massive dose (3,4)or in smaller amounts repeated over a considerable period of time (3)(4)(5)(6).…”

“…The fact also emerges from the numerous trials hitherto reported that resistance is acquired by monkeys when a sufficient amount of active virus is given intra-or subcutaneously in one massive dose (3,4)or in smaller amounts repeated over a considerable period of time (3)(4)(5)(6). Even then protection is not afforded to some animals and the degree of immunity induced varies in others, while now and again a treated monkey succumbs to the disease as a result of the inoculations (1,(5)(6)(7)(8).…”