LIVE POLIO IRUS VACCINES

94
Safety-Laboratory Evidence of Attenuation and Safety
curred in many of the intravenously inoculated
monkeys on days 1, 2, and 3. Two of the intramuscularly
inoculated monkeys (receiving
10 70' PFU of virus) also had viremia on days
1, 2, and 3. Two monkeys which received 10 4.-
PFU of virus intramuscularly (a dose insufficient
to cause histologic evidence of poliomyelitis)
also had viremia on days 5 and 7. Viremia
occurring on days 1, 2, and 3 after intramuscular
inoculation may not be indicative of virus multiplication
and secondary appearance in the blood
but rather of immediate spill-over into the bloodstream.
However, that viremia which occurred
on days 5 and 7 may indicate secondary entrance
of the virus into the blood.
In order further to study the invasive properties
of these strains, a group of monkeys were
anesthetized using intraperitoneal or intravenous
sodium pentobarbital. Then, the right sciatic
nerve was either surgically separated and the
ends tied off or it was frozen with dry ice according
to the method of Bodian and Howe 0.
Animals were then inoculated in the thigh muscles
or in the gastrocnemius of the leg innervated
by the nerve that had been injured. Table
5 indicates the results. The animals having
lesions of poliomyelitis are all in the group having
surgical section of the sciatic nerve and
inoculation in the area of inflammation resulting
from surgery. In animals inoculated at a
great distance from the surgery no lesions occurred.
As a further investigation of the route of invasion
of the CNS, a group of Cynomolgus
monkeys were given human poliomyelitis immune
globulin into the gastrocnemius muscle in
a dosage of 1 or 2 ml. per Kg. of body weight
intramuscularly 24 hours before being given
Lederle Type 1 or Sabin Type 1 intramuscularly
in the opposite leg. The methods used
were those of Nathanson and Bodian 7. Table 6
shows the results of this study. As can be seen,
the paralytic rates and histologic findings were
essentially the same with or without the globulin,
suggesting that the antibody did not protect
these monkeys in any way.
Finally, two monkeys were subjected to the following:
After anesthesia, the sciatic nerve was
injured by freezing and immune globulin was
administered, as previously, in the other leg.
Twenty-four hours later, Lederle Type 1 virus
pool was inoculated into the gastrocnemius muscle
of the leg that had had the nerve surgery.
These animals showed weakness of the leg due
to the nerve injury. Histologic examination of
the spinal cord and brainstem showed no evidence
of poliomyelitis.
Thus it appears likely that the virus has the
capacity to spread to the CNS along peripheral
nerves. Certain facts, however, such as the de-
TABLE 5.
VIRULENCE OF ATTENUATED POLIOVIRUS STRAINS FOLLOWING INTRAMUSCULAR INOCULATION
AND SCIATIC NERVE INJURY
TYPE 1
Virus Inoc. Inoculation Type of Histologic Findings
strain PFU i site Nerve injury Lumbar Cervical Brainstem
Lederle 108.9 Thigh muscles surgical 2/4* 0/4 1/4
sect ion
Lederle 10 8 .2 Thigh muscles surgical 2/4 0/4 0/4
section
Sabin 10 8 . 7 Thigh muscles surgical 2/4 0/4 0/4
section
Sabin 108.0 Thigh muscles surgical 1/4 0/4 0/4
Section
Lederle 10 8 . 2 Gastrocnemius freezing 0/2 0/2 0/2
* No. of monkeys having findings/No. inoculated.