smallpox vaccine and vaccination in the intensified ... - libdoc.who.int

conclusion that smallpox could be eradicated
bv the effective use of the vaccine then
available. Not only did it see no need for a new
vaccine but it also feared that the trials that
such a product would have to undergo would
act as a brake on the global eradication
programme. Since, despite the tremendous
amount of work involved in coordinating this
programme, the unit at its largest consisted of
only 6 professional and 4 supporting sta&
extremely careful attention had to be given to
the determination of priorities.
However, advanced industrial nations
which had eliminated smallpox decades
earlier saw the problem from a different perspective.
Health officials and the public alike
were concerned by the sickness, occasional
complications and,rarely, death that followed
the administration of existing smallpox vaccines.
Virology had advanced a long way
since 1798. when vaccination had first been
introduced, and many workers, especially in
Europe, Japan and the USA, sought a vaccine
that would be associated with milder lesions
after primary vaccination and especially with
less likelihood of complications.
Methods of improving smallpox vaccine,
from the point of view of reducing complications,
were extensively discussed; first,
in 1969, at a symposium on smallpox organized
in Zagreb by the Yugoslav Academy
of Sciences and Arts, (GuSiC, 1969) and
again in 1972, when a special session on
smalloox vaccination was convened in
~ilthkven by the International Association
of Biological Standardization (Regamey &
Cohen, 1973). Three approaches were adopted
in the studies designed to develop less
reactogenic vaccines : (1) selection of the least
reactogenic strains from among those currently
being used for vaccine production;
(2) development of an attenuated strain ; and
(3) use of inactivated vaccine. The second and
\,
third approaches included attempts to develop
a method in which attenuated or inactivated
vaccine was first used to orovide an
initial immunological stimulus and thus partial
protection, followed by vaccination with
the usual smallpox vaccine, a procedure
which should in theory reduce complications.
A fourth series of investigations, largely
independent of the issue of vaccinial complications,
was aimed at developing a tissue
culture vaccine which, unlike vaccine of
animal skin origin, would be sterile. None of
these attemots resulted in an alternative
vaccine whith could be widely used for the
11. VACCINATION IN THE INTENSIFIED PROGRAMME
581
global smallpox eradication programme.
Nevertheless, the efforts of laboratory investi-
gators and epidemiologists in these once
important research activities are significant
for the historical record. If attempts to
immunize human beings against a variety of
diseases by the incorporation of designated
foreign genes in vaccinia virus are successful,
there will be renewed interest in methods of
reducing the incidence of severe complic-
ations.
Selection of Vaccinia Virus Strains of Low
Pathogenicity
Polak et al. (1963) reported on the pathogenicity
to man of vaccines made with the
Bern, Copenhagen, Ecuador and Lister
strains of vaccinia virus. The generalized
responses, in terms of the degree of morbidity
(the ratio of number of bed-patients to
number of successful vaccinations), high
fever, and prolonged fever in bed-patients,
were recorded. The Lister strain ~roduced the
mildest response, followed by ;he Ecuador
strain. The Copenhagen and Bern strains were
similar in their effects and of greater pathogenicity
than the other two. Thus, when a
sound evaluation method was used with
adeauate controls. it was demonstrated that
1
vaccinia strains differed in their pathogenicity
to man. In addition, the study suggested
that the potency of the vaccine (in terms of its
titre) seemed tdhave no bearing on the course
of illness following vaccination. These results
supported the views held by many epidemiologists
that different strains of vaccinia virus
were associated with different frequencies of
complications (see Chapter 7). For example,
the Bern strain. once used in Austria. Germany,
Switzerland and Yugoslavia, had been
associated with much higher complication
rates (especially of postvaccinial encephalitis)
than those reported in the United Kingdom
(in which the Lister strain was used) or the
USA (in which the New York City Board of
Health strain was used). By 1971, these
countries, with the exception of Yugoslavia,
had changed to the Lister strain for vaccine
production, and from that time on the
complication rates decreased.
In the 1960s. Dr Marennikova and her
colleagues in Moscow collected vaccinia
U
strains from different vaccine producers and
studied their pathogenicity, as determined by
inoculation by various routes into rabbits,
mice and irradiated rats. Table 11.20 sum-