0100489061

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RESEARCH ON DENGUE IN TISSUE CULTURE : IV. Serologic Responses of Human Beings to Combined Inoculations of Attenuated, Tissue-Cultured Type I Dengue Virus and Yellow Fever Vaccine

English (英語)

The Kobe journal of the medical sciences

15(4)

163-180

1969-12

Using a human-attenuated, tissue-cultured type 1 dengue virus (Dl, Mochizuki strain) in combination with the yellow fever (YF) 17D virus vaccine, human immunization experiments were carried out as an extension of the previous work (reported in this JOURNAL, 12, 199, 1966). Preliminary data indicated that Dl virus multiplied in trypsinized dog kidney cell cultures. Degree of CPE in the infected cultures was slight. Specific hemagglutination-hemadsorption with goose erythrocytes, however, was positive. Adults who were residing in the main islands of Japan and who had never entered dengue or YF-endemic areas were divided into the following 5 categories: (A) those inoculated with live Dl and YF viruses simultaneously; (B) those inoculated, first with Dl virus, and two weeks later with YF virus; (C) those inoculated, first with YF virus, and two weeks later with Dl virus; (D) those inoculated with Dl virus, alone, which had been cultivated in Japanese monkey (Macacus fuscatus) kidney cell cultures; and (E) those inoculated with Dl virus, alone, cultivated in dog kidney cell cultures. Two shots for each virus were given at 10-week intervals. No abnormal clinical signs were recognized after the inoculations. Serum was taken from each subject and neutralization (NT) and hemagglutination-inhibition (HI) antibodies were measured. Fractionation of serum by sucrose density gradient centrifugation (Suc-DGC), together with a 2-mercaptoethanol (2-ME) treatment were also performed. Both anti-Dl and anti-YF NT and HI antibodies were effectively produced after combined inoculations of the two viruses. At the same time, the following tendencies were noted : (i) When the Dl and YF viruses were inoculated simultaneously, titers of anti-Dl antibodies were somewhat lower than those produced after inoculating Dl virus alone; (ii) the similar aspect was shown in the subjects inoculated first with YF virus and two weeks later with Dl virus; and (iii) in the subjects inoculated first with Dl virus and two weeks later with YF virus, titers of anti-Dl antibodies were of the same magnitude as those produced by inoculating D1 virus alone. It appeared, at least under the conditions studied, that titers of antibodies against virus given afterward were lower than those against virus given previously. Intracutaneous inoculation of comparatively small doses of live D1 virus cultivated in dog kidney cell cultures provoked production of anti-D1 antibodies of significant titers. General patterns of such antibody production were essentially the same as those by the same virus of monkey kidney cell culture origin. Serum specimens taken at 5 weeks after the first virus shot (i.e., taken at the "first peak" of antibody rise) and those at 12 weeks (i.e., at the "second peak" of antibody rise after the booster shot) were subjected to Suc-DGC and 2-ME treatment. It was indicated that major portions of the antibodies detectable at 5 weeks corresponded to 19S globulin and were ME-sensitive whereas those at 12 weeks corresponded to 7S globulin and were ME-resistant. The majority of the sera tested had anti-Japanese encephalitis antibodies which, however, apparently showed no direct correlation with the anti-D1 and anti-YF antibodies detected in the present study.

vaccine

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