LIVE POLIO IRUS VACCINES

Studies on Live Poliovirus Vaccine in Japan
193
the IS route. Prior to the use of such a low
virulent strain as a vaccine, there were many
tests to prove the strain to be safe in neurovirulence
and in genetic stability, and not to be
contaminated with other viruses.
At present, attenuated vaccines have been developed
through the efforts of Dr. Sabin,' Dr.
Koprowski,3 and Dr. Cox, 4 respectively. The
use of these vaccines is supported by basic
studies, and by small- or large-scale field trials
in various parts of the world, especially in Singapore,
where mass vaccination was carried out
with significant results without accident. These
results encouraged me to make up my mind to
use, without fear of risking an accident, the live
poliovirus vaccine in the field in the known endemic
area. Since 1957, I have requested permission
from the Welfare Ministry several times
to use the oral vaccine in the field. The answer
was that it was not yet the proper time for its
use, since it was unreliable in genetic stability
and because of the probability that it might
convert into the wild strain. However, both
kinds of vaccine, one being a frozen virus suspension
and the other in the form of granules contained
in a capsule, were already at my disposal
through the courtesy of Dr. Sabin and Dr. Cox,
respectively, as requested by us.
The Sabin vaccine was preserved in a deep
freezer (-200 C.) and the Cox vaccine was kept
in the refrigerator until used. A part of the Cox
vaccine was given to Dr. Nishizawa of Osaka
University for its trial on infants and for experiments
on monkeys. Since 1959, Dr. Enjoji of
Fukuoka University has been joining our study
groups on live poliovirus vaccine in Japan and
has been trying to administer both types of the
Cox vaccines (monovalent and trivalent), to infants.
Thus, Dr. Nishizawa, Dr. Enjoji, Dr.
Asano (First National Hospital), and I had carried
out the vaccine trial in volunteers in each
hospital to follow up any side reaction, to ascertain
the extent of immunity and its duration, and
to check antigenic stability of the virus excreted
by the vaccinees, as well as the duration of virus
excretion and spread of virus excreted among
contacts, before the Welfare Ministry decided to
grant permission for field trials. In the meantime,
the Welfare Ministry showed a tendency
toward granting tacit permission to use the vaccine
in the field, supervised by myself. Nagaoka
City, Niigata Prefecture, and Kobe City, Hyogo
Prefecture, were selected for the vaccine trial
started last March and April. This paper represents
the outline of the results so far obtained on
live poliovirus vaccine in Japan.
The Cox monovalent vaccine. Eight children,
six males and two females, aged from one year
and five months to eight years and three months,
all staying in the same room, were fed successively
with one capsule each of Type 1 and Type 3,
and then two capsules of Type 2 Cox monovalent
vaccine, at four-week intervals. The virus titers
of Types 1, 2, and 3 vaccines were estimated at
4.0 x 10', 3.2 x 103, and 1.1 x 102 plaque-forming
units per capsule, respectively. These titers might
be underestimated owing to the technical difficulties
encountered in separating viruses from
granules in capsule.
Blood samples for the determination of neutralizing
antibody were taken once just before
initial feeding, and three times every four weeks,
after successive feeding of eachl monovalent vaccine.
Virus isolation attempts were undertaken
from stools collected weekly for 12 weeks after
the initial feeding. As a whole, an antibody
rise was recognized in all vaccinees except one
fed with the Type 3 vaccine, and some of them
showed a titer of more than 7940. It seems likely
that the administration of Type 1 vaccine
stimulated formation of antibody against Type 2
and viceversa, but poorly for Type 3 poliovirus
(Table 4).
Fourteen strains of Type 1 poliovirus, three
strains of Type 2, and 13 strains of Type 3
were isolated. Most of them were isolated for
three weeks after feeding and persisted for six
weeks (Table 5).
The virus isolation from stools was found to be
strongly influenced by the status of each child,
that is, three types of virus were usually isolated
from a triple-negative child. If the vaccinee has
not the naturally acquired antibody against any
type of poliovirus, the virus corresponding to the
deficient antibody can be isolated without difficulty,
following oral administration of live poliovirus
vaccine. However, it can be observed that,
with an antibody titer for Type 1 or Type 2 poliovirus
as high as 1:51-1:1300, sometimes the remaining
type of poliovirus could not be isolated,