LIVE POLIO IRUS VACCINES

18
Safety-Laboratory Evidence of Attenuation and Safety
TABLE 5. HISTORY OF MEXICO AND CINCINNATI ISOLATES SELECTED FOR CHIMPANZEE NEUROVIRULENCE
TEST
TYPE, CHARACTER
OF VACCINE FED
DAY AFTER
FEEDING
MEXICO
CHILD # 372
(2 months old)
TYPE, CHARACTER
OF VIRUS EXCRETED
----
DAY AFTER
FEEDING
I--------------
CINCINNATI
CHILD KF
(11 years old)
TYPE, CHARACTER
OF VIRUS EXCRETED
Polio 1
d-T-
7
14
21
Polio 1 d+T-
Polio 1 d+T-
Negative
5
17
Polio 1
Polio 1
d-Td+T-
[Polio 3 d-T- ]
7
14
21
Polio 3 d+T-
Polio 3 d+T+
Polio 3 d+T+1
Spec. 2576
6
20
Polio 3 d+T+
Polio 3 d+T+1-
Spec. S-33
Polio 2
d-T-
7
14
Negative
Negative
10 Polio 2 d+T-
20 Polio 2 d+T-
[ ] Indicates strains tested in chimpanzees.
in neurovirulence, especially in the intracerebrally
inoculated monkeys.
Cytopathogenic virus was recovered from the
spinal cords of almost all monkeys sacrificed
soon after the onset of paralysis, indicating that
no selection of strictly neurotropic virus had
taken place in the CNS of the monkeys.
Two Type 3 d+T+- strains shown in Table 5
(one recovered from a two-month-old vaccinated
child in Mexico City, and one from an 11-yearold
child vaccinated in the winter in Cincinnati
by Sabin) were selected for inoculation not only
in monkeys, but also into chimpanzees, as members
of this species are known to be much less
sensitive to intraspinal administration of attenuated
poliovirus than monkeys. As shown
in Table 6, we confirmed Sabin's results with
the vaccine, in that the d-T- vaccine itself
was negative when undiluted material was injected
intraspinally into the chimpanzee. The
d+T+ isolates, however, wroduced paralysis and
severe cord lesions.
Figure 2 is a diagrammatic expression of the
intraspinal virulence of the vaccine strains and
the isolates which were studied. The per cent
of monkeys with polio is expressed as a function
of the virus dose used. One can observe
that the curve for the d-T- isolates does not
differ much from the curve obtained with the
vaccine strains. On the other hand, there is a
minimal difference between the d+T+ isolates
and those which underwent change in the d
character only (d+T- isolates). Both types of
isolates underwent a shift of about three logs
towards increased neurovirulence, i.e., they are
one thousand times more virulent for the monkey
spinal cord than the vaccines which were administered.
Data of this type bring up the question
of whether the CNS of the monkey could
act as a medium to encourage further changes
in modified strains of the d+T- type and only
completely altered d+T+ particles would then
continue to multiply and produce paralysis in
the inoculated animals. If such were the case
one would expect the spinal cords of such
animals to yield only T+ progeny. If not, a
question remains as to the correlation between
the T marker and monkey neurovirulence.
Passage of T- Virus in Monkey Spinal Cord.
To elucidate this question we undertook to study
the character of isolates possessing a T-
marker linked to a d+ marker and pathogenic
for monkeys, after propagation in the monkey
spinal cord. Such T- isolates were inoculated