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LIVE POLIO IRUS VACCINES

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76<br />

Safety-Laboratory Evidence of Attenuation and Safety<br />

(c) Virus isolation from CNS: With Types 1 third week of the observation period. Particularly<br />

and 2 of the Sabin strain no virus could be<br />

isolated from the central nervous system of any<br />

of the animals (lumbar and cervical cord, brain<br />

stem, precentral gyrus) at the end of the observation<br />

period. With Type 3 isolation attempts<br />

in the animals dying intercurrently polio-<br />

myelitis virus was occasionally also found in the<br />

absence of characteristic histological alterations.<br />

The virus strains isolated from the central<br />

nervous system were examined with reference to<br />

were successful in two cases. With Cox's Type tissue-culture markers d, T, and MS. These<br />

1 strain, virus could be isolated from the CNS examinations appeared promising since in addition<br />

of the monkeys inoculated intraspinally in<br />

to possible mutations of the virus inoculated<br />

numerous cases, not however in animals following<br />

I.C. inoculation. With Cox's Type 2, virus neurotropic poliovirus particles also had to be<br />

the selective effect of central nervous system for<br />

was isolated in more than half of the cases at<br />

considered. With all strains in which an examination<br />

was possible, some of the cases showed al-<br />

the end of the observation period; with Type 3<br />

in only two monkeys who died during the observation<br />

period (indicated by an asterisk, see<br />

terations of one or two markers in comparison<br />

to the initial material. In no instance did these<br />

Table 4).<br />

cases approach the behavior of the virulent<br />

In the monkeys found positive, virus isolation<br />

strains used for controls, however. Compared<br />

was successful in one or more; seldom, however,<br />

in all areas of the central nervous system<br />

with the other strains, the low number of<br />

examined. The virus concentration was lower<br />

changes in genetic behavior found with Cox's<br />

than that found in corresponding areas after inoculation<br />

Type 2 strain was remarkable.<br />

of virulent strains. A comparison of (d) AntiWody formation in animals: With all<br />

the frequency of positive virus findings with the<br />

severity of histological lesions in general showed<br />

strains there appeared to be a relation between<br />

the production of antibodies and the virus concentrations<br />

parallel results. Virus isolation was successful<br />

administered. There was no differ-<br />

especially in those cases in which motor weakness<br />

ence in the results with I.S. and I.C. inoculation,<br />

was still pronounced during the second or however. Antibody formation did not seem<br />

to<br />

TABLE 5.<br />

DILUTION<br />

TYPE<br />

ROUTE<br />

10 °<br />

10-'<br />

10-2<br />

1<br />

I.S.<br />

I.C.<br />

2/3<br />

3/5<br />

0/4<br />

1/5<br />

0/5<br />

0/5<br />

o<br />

2 I.S. 2/4 1/5 0/5<br />

I.C. 3/5 3/5 0/5<br />

3<br />

I.S.<br />

I.C.<br />

1/5<br />

1/5<br />

1/4 0/5<br />

2/5 0/5<br />

1<br />

I.S.<br />

I.C.<br />

0/5<br />

2/4<br />

1/4 0/3<br />

2/5 0/5<br />

._<br />

-m e<br />

2<br />

I.S.<br />

I.C.<br />

4/4<br />

1/3<br />

2/4<br />

2/5<br />

0/4<br />

1/5<br />

3<br />

I.S.<br />

I.C.<br />

1/4<br />

0/4<br />

0/4<br />

0/5<br />

0/5<br />

0/5<br />

No. of monkeys with antibodies/No. of inoculated monkeys.

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