LIVE POLIO IRUS VACCINES

Experimental Studies on Animals with Attenuated Poliovirus
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depend on the extent and occurrence of central
nervous system lesions, i.e., animals in which I.S.
inoculation did not reach the grey substance of
the lumbar cord, also showed antibody formation.
Differences between the strains examined
seem to occur only with regard to Type 3, of
which Sabin's strain led to antibody production
in only one case (see Table 5).
The antibody titer was partly high and in some
cases exceeded a dilution of 1:512. The various
strains showed no difference in the height of
titers.
(e) Virus isolation from feces: 627 specimens
of feces were examined before and during the
experiment. In 206 cases a cytopathogenic effect
could be found in tissue cultures (43 cases
showed the type of cytopathogenic effect found
with adenovirus, in 159 cases it had not yet been
possible to determine the type, in 4 cases poliovirus
was isolated).
Discussion. Our findings with regard to the
neuropathogenicity of the attenuated virus
strains of Sabin and Cox are in agreement with
the results of Murray and Melnick, i.e., all
three of Sabin's intraspinally inoculated strains
are less neuropathogenic than those of Cox. This
difference was most striking in the Type 2 strains,
whereas there was no difference following intracerebral
inoculation of Type 1 strains of Sabin
and Cox.
A comparison with Murray's findings regarding
the extent of neuropathogenicity showed
that in our examinations Cox's Type 1 led to
less pronounced histological lesions in the central
nervous system. Results with Types 2 and
3 of Cox tallied quite well with the findings of
Murray. With Sabin's Types 2 and 3 strains,
the alterations found by us were similar to
Murray's findings. This was also the case with
Type 1 following I.C. inoculation. Following
I.S. inoculation, the alterations found by us
were less pronounced.
A comparison of our findings with those of
Cabasso using the Cox strains revealed a higher
degree of neuropathogenicity following I.S. inoculation
of Type 1. There was no difference
in results following I.C. inoculation. With Type
2 we found histological alterations more frequently
than Cabasso following I.S. as well as
I.C. inoculation. A comparison of results with
Type 3 was not possible.
An attempt to isolate the virus from the central
nervous system after the end of the observation
period showed striking differences between
the various strains. The rate of successful
isolations essentially paralleled the neuropathogenicity
found by histological examination.
The examination of genetic properties of isolated
strains using markers d, T, and MS occasionally
showed slight alterations of some
characteristics in comparison to the initial material.
Cox's Type 2 seems to possess the greatest
stability with respect to the examined genetic
markers.
There was no difference in the production of
antibodies following I.C. and I.S. inoculation;
particularly, there was no relationship with the
occurrence and extent of histological lesions in
the central nervous system. Noteworthy was the
fact that antibody production was rare following
inoculation of Sabin's Type 3 strain. No
connection was found between antibody production
and the frequency of isolation of non-poliovirus
from the feces of the animals. The antibody
formation is regarded as proof of a multiplication
of virus outside of the central nervous
system, with the spreading of the virus obviously
taking place directly via the inoculation trauma.
The validity of this statement was supported by
the results of experiments on the inoculation
of india ink into the central nervous system.
Finally we would like to raise the question of
whether, in addition to the usual methods of testing
the neuropathogenicity of virus, other criteria
might also be useful in assessing the suitability
of strains for human vaccination. Of
these, one might name the obvious multiplication
of virus in the central nervous system, the
ability to multiply outside of the central nervous
system and the genetic stability of virus
strain following passage in neural and extraneural
tissue.
CONCLUSION
By intracerebral and intraspinal inoculation of
monkeys with the attenuated poliovirus strains
of Sabin and Cox it was shown that all three
of Sabin's strains are less neuropathogenic than
those of Cox. These results are in agreement with
the findings of Murray and Melnick.
At the end of the observation period of 21
days, the results of virus isolations from the
central nervous system paralleled those on neuropathogenicity
as manifested by histological alter-