LIVE POLIO IRUS VACCINES

6
General Considerations
immunity and thus prevent the carrier state in
poliomyelitis? Resistance of 10 out of the 12
vaccinated children to reinfection provided an
affirmative answer. It was suggested then and
later confirmed that immune children occasionally
became infected, and then only transiently.
Yet another question was raised in 1950:
would the administration of one type of vaccine
provide protection against poliomyelitis of another
type? At last year's Conference you
heard about the ambiguous results of a trial in
Singapore based on this speculation."l
The vaccine strain tried in 1950 was chosen
on the basis of its relatively low pathogenicity
for monkeys when inoculated intracerebrally. At
the same time, however, it was recognized that
it was "impossible to draw a definite . . . parallel"
between "innocuousness" for monkeys and
safety for human beings.
Sabin's introduction of intraspinal testing, '2
and Melnick's refinement of the technique 13
still in monkeys-provided a more sensitive index
of pathogenicity for monkeys, but the significance
and relevance of this increased sensitivity
were not clear. The results of intraspinal testing
in the hands of different investigators are
still contradictory, and the importance-indeed,
the necessity-of acquiring comparative data
which would define attenuated and naturally occurring
polioviruses in terms of monkey neuropathogenicity,
has been increasingly recognized.
A further question noted then has concerned
many workers since: How stable is the vaccine
strain after passage through the human alimentary
canal? The initial observations on this
point indicated that the virus excreted in the
feces "retained about the same degree of virulence
for monkeys" as did the original vaccine
strain.
Finally, it was pointed out in the 1952 paper
that the establishment of attenuated poliovirus
as an immunizing agent hinged on larger trials,
in which safety could be evaluated with statistical
validity, allowing for the chance probability
of unrelated illnesses in vaccinated persons.
Thus, as you can see, although attenuated live
vaccine research has progressed to a stately
round of international conferences, the questions
and problems raised at them are not new
concerns.
Choice o/ subjects. With the important exception
of certain cases I shall mention, the
s
multiplication of vaccine virus in the intestinal
tract is regularly associated with antibody production.
Moreover, the presence of circulating
antibodies, except those produced by infection
with living poliovirus, do not interfere with immunization.
Of practical and theoretical importance
within this context were the observations by
Lipson et al.,' 4 by Horstmann et al. 5 , and by
Fox and Gelfand,16 that previous vaccination
with inactivated virus neither interferes with subsequent
immunization by live virus nor has any
substantial effect in preventing subsequent intestinal
infection with natural poliovirus. Perhaps
even more important for the future were our related
obsarvations, made in 1955 and 1956 and
since confirmed by Martins da Silva and others' 7
that homotypic maternal antibodies in the circulation
of newborn infants do not interfere with
the establishment of intestinal infection by live
attenuated poliovirus.
Whether or not it will be possible to take the
ultimate step of routinely immunizing children
on the first or second day of life is an unsettled
matter, for we will show later in this Conference
that infants in the first few weeks of life are
relatively deficient in their ability to produce
antibodies in response to the stimulus of intestinal
infection with attenuated polio vaccine.'
, 19 The situation in newborn infants represents
the only case in which we have found a
dissociation between infection with attenuated
virus and antibody response. And while increasing
the dosage of the virus may overcome the
relative resistance of infants less than three
months old to intestinal infection with poliovirus,
it is doubtful that the intrinsic relative
immunologic incompetence of the newborn infant
can be overcome easily.
The subject of infectiousness brings us to
another crucial area of investigation. On the
basis of the evidence at hand, immunization with
attenuated poliovirus may be accomplished without
viremia. However, this area of research invites
further study from the theoretical point of
view, now that more sensitive methods for detecting
circulating virus are available. Since
some aspects of the pathogenesis of poliomyelitis
infection in man are involved in an enigma, we
are exploring the problem of viremia and pathogenesis
by plotting the pathway of infection with
attenuated strains in man by following the ap-