LIVE POLIO IRUS VACCINES

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TOPIC II. SAFETY. (A) LABORATORY EVIDENCE
OF ATTENUATION AND SAFETY
1. PROBLEMS ASSOCIATED WITH LIVE POLIOVIRUS VACCINE
AND ITS PROGENY AFTER MULTIPLICATION IN MAN *
JOSEPH L. MELNICK AND MATILDA BENYESH-MELNICK
Department of Virology and Epidemiology, Baylor University
College of Medicine, Houston, Texas
DR. MELNICK (presenting the paper): The
ultimate safety of live poliovirus vaccine rests
on the long-term results of its use in the field.
Safety must be evaluated on the basis of the
vaccine being used in fully susceptible persons
-those who have lost maternal antibodies, and
who have never been infected naturally or who
have never received inactivated vaccine.
However, regardless of the field experience,
the laboratory serves an essential function in
supplying information on the properties of the
virus in the vaccine, particularly whether these
properties remain constant in successive manufacturing
lots, and whether they remain constant
after multiplication in vaccinated human beings.
To be of value, the laboratory methods should
allow us to discriminate among strains according
to their degree of attenuation for monkeys. As
minimal monkey neurovirulence was the only
criterion of safety on which the vaccine strains
were selected for use in man, this property
should not now be glossed over by saying that
it has little or no significance for evaluating the
safety of a polio vaccine. We have no other bona
fide way of measuring the degree of virus attenuation.
Strains which show more neurovirulence
than the most highly attenuated vaccine
strains must be regarded as possessing a somewhat
more dangerous potential for human beings.
This holds if we compare one strain with
another as candidates for incorporation in the
vaccine, or if we compare the vaccine virus
* Aided by a grant from The National Foundation.
with its progeny after multiplication in the
intestinal tract of a vaccinated child. Just how
much of a departure, or reversion, from the
highest degree of attenuation can be safely tolerated
in man remains an unanswered question,
but by using strains of the highest degree of
attenuation and by using strains which are also
stable genetically, I hope that we shall never
have to answer the question.
Comparison of Candidate Strains for Monkey
Neurovirulence. Two impartial laboratories have
carried out extensive comparative tests with
the Lederle-Cox and the Sabin strains, 1 ' 2 and
their results were reported at the Conference
which met here in Washington last year. The
results are of importance for several reasons.
First, despite many allegations to the contrary,
they show a relatively high degree of reproducibility
of neurovirulence tests in the two laboratories.
Second, the tests in these two laboratories
are more sensitive than those reported by Sabin
and by Cox. Third, they discriminate between
strains possessing different degrees of attenuation.
It is readily apparent that the Sabin strains
are more highly attenuated, for after intracerebral
inoculation they are virtually without
neurotropic activity, and after intraspinal inoculation
they yield less than 10 per cent of the
clinical disease produced by the Lederle-Cox
strains at the same doses.
Other analyses of the neurovirulence data
bear this out. When the intensity of the cord
lesions are graded by our scoring method, t the
lower scores of Sabin strains again show them
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