The development of a live attenuated tetravalent dengue vaccine is currentl
y the best strategy to obtain a vaccine against dengue viruses. The Mahidol
University group developed candidate live attenuated vaccines by attenuati
on through serial passages in certified primary cell cultures. Dengue serot
ype 1, 2 and 4 viruses were developed in primary dog kidney cells, whereas
dengue serotype 3 was serially passaged in primary African green monkey kid
ney cells. Tissue culture passaged strain viruses were subjected to biologi
cal marker studies. Candidate vaccines have been tested as monovalent (sing
le virus), bivalent (two viruses), trivalent (three viruses) and tetravalen
t tall four serotype viruses) vaccines in Thai volunteers. They were found
to be safe and immunogenic in both adults and children. The Mahidol live at
tenuated dengue 2 virus was also tested in American volunteers and resulted
in good immune response indistinguishable from those induced in Thai volun
teers. The master seeds from the four live attenuated virus strains develop
ed were provided to Pasteur Merieux Connaught of France for production on a
n industrial scale following good manufacturing practice guidelines. (C) 20
00 Elsevier Science Ltd. All rights reserved.