LIVE POLIO IRUS VACCINES

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Efficaey-Laboratory Evidence
Efficacy-Laboratory Evidence
10, 14, 21, and 28. From infants in group 6 made at one and two weeks after vaccine feeding
(trivalent vaccine feeding), they were collected
on days: 0, 1, 2, 3, 4, 5, 6, 8, 10, 14, 21, 28,
on all babies designated for detailed study and
those in the illness control group.
35, 42, 49, 56, 63, 70.
Fecal samples were prepared into 20 per cent
extracts by shaking with Hanks' BSS, followed
by slow speed centrifugation in the cold for about
two hours to remove gross particulate matter.
Acid extracts were brought to approximately pH
7.4 by the addition of a drop or two of dilute
NaOH solution, and then stored with antibiotics
in screw-topped vials at -200 C. until tested.
For virus isolation, each of four monkey-kidney
cell culture tubes was inoculated with 0.25 ml.
extract. The tubes were examined every second
day for eight days. If negative at that time,
supernates of the four tubes were pooled, and
0.2 ml. of the pool inoculated into each of two
new MKC tubes. If the passage tubes showed
no evidence of a cytopathic effect after eight days,
the specimen was considered negative for virus.
"Positive" supernates were tested by mixing an
aliquot of a standard 1:100 dilution with potent
Type 1, Type 2, Type 3, polyvalent (three types),
and normal control antisera. These mixtures
were incubated for one hour at room temperature,
and then inoculated into two tubes each of MKC
culture. If the results of this test indicated that
more than one poliovirus type was present, a second
similar test was performed using antisera
with the following mixtures of antibody types:
1 and 2, 1 and 3, 2 and 3, all three types, and
normal control. Combinations of any 2 or 3
types could thereby be identified. It should be
noted that if small quantities of a second virus
type were present in a fecal extract, it might be
missed because of the overgrowth of the predominant
type. Because of this possibility
(among infants fed polyvalent vaccine), mixtures
will be made at a later date of fecal extracts
and antisera against the virus type(s) already
isolated, and a new attempt at virus isolation
will be made. Such retesting has not yet
been done, and the following results may be deficient
to that extent.
Clinical observations. At the time of a home
visit to pick up the sixth-day fecal specimen, the
nurse examined the infant briefly and discussed
with the mother his health during the interval
since vaccination. A formal' health record was
RESULTS
Until the time of this writing (15 May, 1960),
138 babies have received vaccine under one or
another of the indicated schedules, and another
11 have been observed as group 7 controls. There
have been no untoward reactions attributable to
the vaccine, i.e., no diarrhea not readily explainable
on another basis, no febrile or allergic responses,
no symptoms referable to the central
nervous system. Two serious illnesses have occurred
in vaccinated infants, one case of pulmonary
atelectasis, edema, and pneumonitis, perhaps
related to congenital cardiac defects, which
terminated fatally, and one case of hemolytic
jaundice probably caused by severe bacterial infection.
Infection has thus far been investigated only
by the attempt at virus isolation, and for those
infants in the "limited study" category only one
specimen (six days after vaccine administration)
was available. It is therefore possible that some
infections have been missed, and will be picked
up only upon serologic examination later. No
virus cytopathogenic in monkey-kidney cell tissue
culture has been detected in a fecal specimen
collected prior to feeding, but two enteroviruses.
as yet unidentified but not poliovirus, have been
found in the excreta of children 28 days after
vaccine administration, who were 30 and 56 days
of age, respectively. Before it was realized that
a fecal specimen collected several hours after
oral vaccination was unsuitable, several were obtained
at two, four, or six hours after administration
when none was available at the time of
feeding. In almost every such instance, homologous
virus was isolated from the feces, undoubtedly
representing the very rapid intestinal passage
of vaccine.
As results were accumulated in the laboratory.
changes in the study protocol seemed justified,
and new recruitment goals were established, as
indicated in Table 2. (See Table 1 for description
of subgroups.) Because the end-point of
infectivity had not been reached for any of the
vaccine types, new subgroups ld, 2d, and 3d were