LIVE POLIO IRUS VACCINES

16
Safety-Laboratory Evidence of Attenuation and Safety
fashion at last year's Conference. Homotypic
strains isolated from test children at different
periods after vaccination were subjected to the
d and T tests and the results obtained are illustrated
in Table 2.
When a strain reverted from d- -- d+, it
was not always associated with a T- - T+
reversion. However, a T- -- T+ reversion was
usually linked with a d- -- d+ or a d- -> d +
reversion. An illustration of the degree of alteration
in the homotypic polioviruses excreted by
orally vaccinated children is shown in Table 2.
Homotypic virus indicates poliovirus of the same
type as that in the vaccine fed, and excreted
after the feeding. The table includes the code
numbers of the children, the types of virus
isolated in their pre- and post-feeding specimens,
and the d and T characters of the homotypic
polioviruses excreted. The squares around some
of the poliovirus isolates indicate those which
were tested in monkeys.
It can be seen that the first two children in
this table, who excreted poliovirus for several
weeks, revealed a change from d to d+ character
in their third and second isolates, respectively,
with no change in the T character. On the other
hand, children Nos. 372, 376, and 126 excreted
d+T- viruses in the first week after feeding,
thus indicating an early alteration of the vaccine
virus in at least one character, during multiplication
in the intestinal tract. The majority
of the Type 3 isolates were of the d+T- character,
and some underwent further reversion to
d+T+, while the frequency of change in the
Type 2 isolates was similar to that of the Type 1
strains isolated.
Summarized below in Table 3, are the results
on 85 strains recovered from vaccinated
children. In 23 strains, there was no detectable
alteration in the virus, in 46 others, the recovered
virus changed in the d but not in the T marker,
and in 16, changes occurred in both markers.
Thus in 19 per cent of the specimens isolated
from children infected with d-T- strains, the
virus had changed in at least two properties.
As indicated at last year's Conference, we
selected strains with different degrees of alteration
in these two markers for monkey neurovirulence
tests. The strains had all been isolated
in monkey kidney cultures maintained at pH 7.4.
However, to insure that we were not selectively
enhancing the proportion of monkey paralytogenic
strains by passage of the human virus in
tissue culture, a number of rectal swabs obtained
from the vaccinated children were inoculated
directly into monkeys by the intraspinal route.
The dose of virus in such material which could
be inoculated was very small indeed, varying
from only 10 to 60 TCD 50 , so that selection of
virulent viruses from a tremendous excess of
thousands or millions of avirulent virus particles
by the monkey CNS does not play a role in these
results.
A summary of the monkey tests to date on
strains of the 3 types is shown in Table 4. It is
apparent that excreted strains which retain the
d-T- markers of the vaccine virus are not
significantly more virulent for monkeys than
the vaccines themselves, about 10,000 TCD 50
being required to paralyze 50 per cent of the
monkeys inoculated intraspinally, and no illness
being produced by undiluted tissue culture fluid
inoculated intracerebrally. The d+T- strains
show increased activity, both intraspinally and
intracerebrally, when compared to the d-Tvaccine
virus. Thus only 10 TCD 50 of the
cultured virus produced paralysis and lesions
in 6 of the 16 monkeys inoculated intraspinally,
and some of the strains were also active after
intracerebral inoculation. Furthermore, 10 to
60 TCD 50 of virus in the rectal swabs themselves
produced paralysis in a significant number
of test monkeys inoculated intraspinally. The
d+T+ strains showed even greater increases
TABLE 3.
CHARACTER OF HOMOTYPIC POLIOVIRUS EXCRETED BY VACCINATED CHILDREN
VIRUS
TYPE d-T- d-T- d+T- d+T± d+T+ TOTAL
Polio-1
Polio-2
Polio-3
Total
19
3
1
23
9
3
0
12
9
17
8
34
o
2
2
4
o
o
12
12
37
25
23
85