LIVE POLIO IRUS VACCINES

50 Discussion
sages of neurovirulent strains which we got from
the intestinal tract of children.
Even if we observed an increase of neurovirulence
for monkeys, we continued to feed
this material to triple-negative children so- as
to follow the fate of this neurovirulence.
As I mentioned previously, as a rule, this
neurovirulence of virus disappeared in the following
passages, so that the intestinal tract of
other children did not continue to support these
neurovirulent viruses. There is no indication of
a progressive increase of neurovirulence. This
quality appears and then disappears.
We did not conduct lengthy sub-passages of
this strain on cell cultures because our aim was
to get quantitative information on the changes
in neurovirulence, to which I am referring at
the moment.
At the present. time, we are trying to establish
the correlation between these neurovirulent
viruses and their pathogenic meaning. Can they
be more invasive through the intestinal tract and
produce more pronounced viremia? Viremia,
so common in naturally infected children, is not
found in vaccinated children.
DR. DULBECCO: I should like to make a comment
on what Dr. Smorodintsev has just said,
namely, the failure of passing further the pathogenic,
neuropathogenic characters for monkeys
with the virus obtained from those children in
which the passage of the vaccine virus was
shown to be increased in neurovirulence. I think
that this failure of continuing the passage of
neurovirulence may be interpreted in a different
way: it could be due simply to a statistical sampling
problem.
In fact, 10' tissue-culture doses are an adequate
dose to cause infection with the vaccine,
but if much less than that is inoculated one will
not have a positive result all the time. This
means that 105 tissue-culture doses are essentially
equivalent to probably a few effective
doses, which, by the oral route, can give rise to
extensive intestinal multiplication and cause antibody
production.
We may therefore consider that 105 tissueculture
doses probably correspond to a few
infectious doses for the child.
Now, the virus which comes from the feces
contains a small proportion of neurovirulent
virus; of this you inject a large dose intracerebrally
in monkeys, where the minority virulent
type can be thus detected; but in testing the
child you inject a few infectious doses (for the
child) and therefore you discriminate against
any minority type. The failure of passing further
the character of neurovirulence for monkeys
could simply be due to this sampling process
and may not imply that neurovirulence is actually
lost in subsequent passages.
DR. SMORODINTSEV (through an interpreter):
In connection with the comments just made, I
should like to say that we introduced not 100,
000 doses but rather one and a half logs more.
The average concentration fed to children was
6.5 logs of 10. These were studied quantitatively.
Only those children who gave a high multiplication
of virus introduced into the intestinal tract
were considered by us to be interesting and we
conducted observations on monkeys to titrate
the level of neurovirulence.
Of course, here there can be significant variation
in results for different children, but this
was usual during 12 passages of each of the
three attenuated strains: neurovirulence either
appears or, what occurs more frequently, completely
disappears during subsequent passages.
The same results are observed during the natural
passage of neurovirulent pathogenic strains
which do not select out strains of the greatest
virulence. Rather, there is a distinct predominance
of strains of moderate or low neurovirulence.
CHAIRMAN ANDERSON: The presentation of
papers under Topic II will be continued during
the second session.