LIVE POLIO IRUS VACCINES

Discussion 205
Discussion 205
tried mixing the viruses experi-
DR. SABIN: With reference to the question that
Dr. Dick asked of Dr. Kimball, about the evidence
for multiplication of poliovirus in children that
may have been adequately immunized with properly
spaced doses of Salk vaccine of proper
potency, I carried out a rather extensive study
in association with Dr. Krugman and others.
This study was reported only in abstract form in
the British Medical Journal and also in another
review article.
Then we
mentally, i.e., ECHO-1, and polio 1. If we put in
a little more poliovirus than ECHO-1, we ended
up by getting only poliovirus after two or three
passages. If we put in a little more poliovirus
than ECHO-1, after two or three passages in
tissue culture, we again got only the one that
was originally there in larger quantity.
I therefore believe that this should be kept in
mind in interpreting, or attempting to interpret,
the data represented by possible virus interference.
The persons who were not found to excrete
poliovirus Type 1, let us say, after being fed Type
1, might have been found excreting poliovirus
had the other enterovirus that was found been
neutralized and a search then made for poliovirus.
DR. HORSTMANN: I did understand Dr.
Hammon's questions. I merely wished to point
out that we were aware of the problem outlined
by Dr. Hammon, but attempted to overcome it by
using another technique. By means of the plaque
method applied to the original fecal suspension,
we were able to pick up small amounts of poliovirus
or other enteroviruses which might have
been overgrown in tissue-culture tubes.
Apparently, with the particular ECHO viruses
which were prevalent during our trial, this
problem did not occur in the same way that it
occurred with Dr. Hammon's Type 1 ECHO
virus. We found both ECHO and polioviruses to
be present in only small quantities. So that, after
extensive tests, we concluded that overgrowth of
one virus by another was not a significant problem
with our material, and returned, therefore,
to tube cultures.
I believe it is also worth mentioning that subsequently
we did isolate a number of ECHO and
polioviruses in the same specimen grown in tissue-culture
tubes. The other point which gives
us confidence in the methods used is that antibody
development and the isolation of viruses correlated
so extraordinarily well, within 1 or 2 per
cent of one another; therefore, we feel it is very
unlikely that we missed any polioviruses in the
specimens under the circumstances under which
Dr. Hammon has suggested this might have
occurred.
We selected, first of all, children without
demonstrable antibody before Salk vaccine.
Three doses of Salk vaccine were then given over
a one-year period, with the proper intervals, and
then a summer period went by and they were
tested at frequent intervals during that time.
Because in some of the children there was a drop
in antibody which had appeared after the three
doses, we obtained a particularly potent Salk
vaccine, that was not a commercially-distributed
one, and gave them all a fourth dose.
We thus accumulated a group of about 25
children, most of whom had rather high antibody
titers-many of them 256 to 512 for Types 1
and 3.
They were then fed either Type 1 or Type 3
vaccine, and the multiplication of viruses was
followed quantitatively over a period of more
than eight weeks. The multiplication of Type 1
and Type 3 virus in them was no different from
that in children without any demonstrable antibody.
Furthermore, the antibody response, the
booster response to this multiplication, did not
occur any faster than in children who had not
previously had any Salk vaccine.
We came to the conclusion that with potent
vaccine and four doses, and the antibody produced
at the level indicated, we found no interference
with multiplication of virus.
DR. BODIAN: Since the subject at this time is
the spread of polioviruses, I think it important to
contribute to this discussion something which I
believe has been missing. I believe that a few
years ago Dr. Howe came closest to presenting
what I consider a rational approach to the problem
of inhibition of virus excretion, namely an
assessment of the role of antibody. Dr. Howe
attempted to find the level of antibody which
would inhibit this phenomenon of infection.