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

and it was feared that serial passage of vaccinia
virus in tissue culture might lead to its
attenuation. After 1967, when the Intensified
Smallpox Eradication Programme was initiated,
WHO did not promote the production
of vaccine in cultured cells because it was
realized that the success of the eradication
campaign was heavily dependent on the
production of large amounts of vaccine in
laboratories in developing countries, which
were unlikely at that time to be able successfully
to produce tissue culture vaccine.
In the late 1960s, the WHO International
Reference Centre for Smallpox Vaccine initiated
a development study with Lister vaccine
grown in primary rabbit kidney cells. At the
time this was the only tissue culture vaccine
comparable with conventional calf lymph
vaccine in terms of heat stabilitv. immuno-
2,
genicity and reactogenicity (Hekker et al.,
1973a). The production method was simple
and cheap, the vaccine was sterile and free
from mycoplasmas and other adventitious
agents, and it maintained its potency for up to
8 weeks at 37 "C. The actual reductions in
titre, ranging from loo.* to pockforming
units per m1 after 8 weeks at 37 "C,
were smaller than those of the calf lymph
vaccine tested as a control. The immunogenicity
of this vaccine was tested by measuring
the neutralizing antibody titres in subjects
1 year after primary vaccination, a control
group having been vaccinated with conventional
calf lymph vaccine. All the subjects
produced neutralizing antibody and there was
no significant difference in the results obtained,
as between tissue culture and calf
lymph vaccines. (Hekker et al., 1973b).
Measurement of the antibodv titre 2 months
after revaccination with the tissue culture
11. VACCINATION IN THE INTENSIFIED PROGRAMME 589
vaccine showed an adequate booster effect
compared with the calf lymph control group.
Because of these successful results. a field
trial on a large scale in Lombok, Indonesia,
was jointly organized in 1973 by the Smallpox
Eradication unit, the WHO Regional Office
for South-East Asia and the government of
Indonesia. A total of 45 443 children under
the age of 15 years were vaccinated with tissue
culture vaccine and the results compared with
those for 9061 children of a similar age and
sex distribution who had been vaccinated
with the standard Lister strain calf lymph
vaccine (Hekker et al., 1976). The success rate
with tissue culture vaccine reached 97%
in primary vaccination and 75% in
revaccination (Table 11.24), results comparable
with those obtained with the calf
lymph vaccine.
The children were carefully followed up for
vaccination complications. The only suspected
complication was a fatal case of possible
encephalitis in a 5-month-old girl who had
been vaccinated with tissue culture vaccine,
but in Lombok there were many other
~ossible causes of this disease.
Both this tissue culture vaccine and the
LCl6m8 strain of Hashizume, which was also
produced in primary rabbit kidney cells, met
the WHO requirements for safety, potency
and stability, and were comparable to calf
lymph vaccine in effectiveness for both primarv
vaccination and revaccination. These
2 strains are the only tissue culture vaccines
which have been thoroughly and systematically
investigated in the laboratory and also to
a limited extent in the field. In the Netherlands,
the Lister tissue culture vaccine is kept
as the vaccine stock for emergency use, both
locally and for supply to other countries; the
Table 1 1.24. Take rates following primary vaccination and revaccination with tissue culture and calf lymph
vaccines (Lornbok, Indonesia, 1973)a
Prlmary vacclnatlon Revacclnatlon
Age group Tlssue culture vacclne Glf lymph vaccine Tissue culture vaccine Calf lymph vacclne
(yeam)
Number Take rate Number Take rate Number Take rate Number Take rate
(W (W (W (W
Total 14 677 97.1 2 796 96.9 30 766 74.7 6 265 71.2
a From Hekker et al. (1 976).