LIVE POLIO IRUS VACCINES

60
Safety-Laboratory Evidence of Attenuation and Safety
traspinally injected monkeys. The data shown
in Table 11 seem to indicate that the resulting
cold variants show a low degree of neuropathogenicity
as compared to the original strains, although
the low concentration of virus in a
preparation of the W-3 strain may account for
some of the favorable results. After these preliminary
investigations, the cold variants of the
W-1 and TN strains were fed to non-immune
infants and children. Although a relatively
small number of subjects was involved, the
results shown in Table 12 seem to indicate that
after 13 passages at low temperature, the cold
variant of the W-1 strain was as infectious for
the human intestinal tract as any other Type 1
strain currently in use. On the other hand, the
infectivity of the Type 2 TN virus after 19 passages
at low temperature was not as high as that
of other Type 2 strains available, since no intestinal
infection was produced with virus doses
below 105 TCD 50 .
Type 1 strains isolated from three children
fed the cold variant of the W-1 strain were
passaged once in monkey-kidney tissue culture
and studied for their temperature marker. A
more elaborate procedure, similar to the one
described by Lwoff, was employed. This involved
one-cycle growth curves of intracellular
virus at two different temperatures-37 0 and 40 °
C.-and the results are shown on Figure 1. It
will be observed that the growth curves obtained
at 400 C. with the vaccine strains CHAT and
W1-P and the three strains isolated from human
subjects fed W1-P-207, 210, and 211-are
similar and show marked differences from the
pattern of the Mahoney strain grown at the same
temperature. As expected, there is little difference
between the growth curves obtained when
cultures were kept at 37 ° C. Growth-curve pat
terns established for virus R-1 isolated from a
child fed the CHAT strain, as shown in Figure
2, resembled those obtained with W1-P virus and
TABLE 11. STUDY OF PATHOGENICITY FOR RHESUS MONKEYS INJECTED INTRASPINALLY WITH TYPES 2
AND 3 VIRUSES (THE TN AND W-3 STRAINS) AT VARIOUS PASSAGE LEVELS AT Low
TEMPERATURES
TABLE 12. RESULTS OF ORAL ADMINISTRATION TO CHILDREN OF W-1 AND TN STRAINS AFTER 13
AND 14 PASSAGES AT Low TEMPERATURES
VIRUS
TCDo 50 FED
RATIO OF INTESTINAL INFECTIONS
7.7
5.5
4.5
1_____1_ (~~~~~~~~
TN
5.7
4.7
3.7
1/1
1/2*
3/3
5/7
0/2
0/2
* Failure occurred in a child with pyrexia at the time of virus feeding.