LIVE POLIO IRUS VACCINES

238
Efflcacy-Laboratory Evidence
23 EfiayLbrtr Evdec
The data presented in this paper support the
evidence by Gelfand et al. 8 and Black and Melnick
9 that there exists an antigenic relationship
not only between Types 1+2 and 2+3, but also
between Type 1+3. The results achieved in
studying the heterotypic antibodies incite a certain
caution when evaluating the antibody response
in vaccinated persons in only one sample
taken after all three types of virus were fed. The
character of heterotypic response in persons lacking
pre-existing immunity is unclear. Two possible
explanations must not be omitted. At first,
a very low state of immunity, undetectable even
by the most sensitive tests used but conditioning
a booster effect, might be present. Second, the
possibility of Type 2 infections must be considered
owing to the demonstrated presence of
Type 2 poliovirus in the investigated community.
On the other hand, however, Type 2 virus was not
isolated from any of the serologically investigated
subjects and also the character of antibody
response was usually not typical for Type 2 infections.
There is no doubt that the question of avidity
and its changing character may play an important
role in many aspects of the immunology of poliomyelitis.
The quality of antibodies and its estimation
could be very valuable in evaluating the
effect of different vaccines, and for both epidemiological
and diagnostic purposes.
The concept of changing the character of antibodies
during the establishment of serological
immunity is not generally accepted. We think
that our results give certain support to the existence
of differences in the quality of antibodies in
different stages of poliomyelitis infection. It
seems that in non-immunes antibodies are produced
in the first period of antibody development,
characterized by a considerable lack of ability to
combine irreversibly with viruses. As is shown
in case 18/HB, the prolongation of the incubation
of the virus-serum mixture or the use of IIT
may be without essential effect on the antibody
titer. In the further course, antibodies more
readily combining with viruses developed, while
the level of antibodies forming only unstable
complexes with viruses, was reduced.
A question of special importance is whether the
existence of low avidity antibody is limited during
a short period after the infection, or whether
the low avidity antibody persists for a longer time.
Sabin presumes that low avidity antibody can persist
and that in such individuals the first step of
antibody development, after new antigenic stimulus,
is the transformation of low to high avidity
antibodies. The results achieved in subject
1/HB strongly suggest that at least in this one,
the presumed change in antibody character was
rather a small quantitative change, undetectable
by the serum dilution and point determination
method with CP/6 or pH tests with 100 TCD 5 ,,
of virus.
It is necessary to emphasize that the avidity of
antibodies, as this term is used in serological
studies with polioviruses, is expressed mainly as
a discrepancy between the results achieved in two
different tests, usually in pH and in CP/1 tests.
It was demonstrated ' that the latter test may be
unable to detect low levels of antibodies, without
any regard to their possible avidity. We think
that the pH test should be compared to the CPT
with 3-6 hours of incubation, rather than to the
CP/1 test. The results presented in this paper
show that titers obtained in CP/6 were comparable
to those achieved in pH tests only in
cases with pre-existing antibodies. Therefore.
the relation of titers achieved in pH tests to
titers in CP/6 test may be of some value. Titers
on approximately the same level could indicate
high avidity antibody; the magnitude of differences
might be indirectly proportional to the
antibody avidity.
The varying decreases in antibody titers between
the second and seventh-day readings, associated
with pre-existing immunity state, bring
some evidence that the magnitude of this decrease
may also be helpful in estimating the quality of
antibodies.
When summarizing the general experience
about the changing quality of antibodies, it is
evident that the main problem is still unsolved.
It must be taken into consideration that all our
conclusions and presumptions are based on the
experiments performed with only one strain of
one type in a rather exceptional group of subjects.
Only further experience, utilizing all the
new knowledge about the virus-antibody-cell interaction,
will bring more progress in the study
of antibody avidity, its nature and persistence
and its possible role in the immunity to virus dis-