Kraiselburd E N, Lavergne J A, Woodall J P, Kessler M J, Meier G, Chiriboga J, Moore C G, Sather G E, Pomales A, Maldonado E, Rivera R
Infect Immun. 1981 Aug;33(2):389-94. doi: 10.1128/iai.33.2.389-394.1981.
Four groups of six nonimmune male rhesus monkeys were inoculated subcutaneously with formulations of dengue type 2 vaccine virus DEN-2/S-1. Group A received 1.9 x 10(4) plaque-forming units of vaccine in normal human serum albumin diluent. Group B received the same dose combined with a dengue type 2-immune human serum diluted 1:1,600, beyond its neutralization endpoint of 1:300, but having an immune enhancement titer of 250,000. Groups C and D received 10-fold dilutions of these respective formulations. No migration-inhibitory factor was found when peripheral blood mononuclear leukocytes obtained on day 68 post-immunization from monkeys of all experimental groups were tested. No viremia was detected in any of the monkeys when sera taken on postvaccination days 1 through 12 were inoculated into adult Toxorhynchites amboinensis mosquitoes and LLC-MK2 cells. By day 89, four of the six monkeys had seroconverted by the neutralization test in each of groups A, B, and C, and three of five monkeys in group D (one monkey died from cardiac collapse after anesthesia) had seroconverted. Immune enhancement of dengue virus infection is known to occur in humans and monkeys circulating heterologous flavivirus antibodies. In this study, there was no enhancing effect when antibody was mixed with dengue type 2 vaccine virus and injected subcutaneously.
将四组每组六只未免疫的雄性恒河猴皮下接种2型登革热疫苗病毒DEN-2/S-1制剂。A组在正常人血清白蛋白稀释液中接种1.9×10⁴ 蚀斑形成单位的疫苗。B组接种相同剂量的疫苗，并加入1:1600稀释的2型登革热免疫人血清，该血清超过其1:300的中和终点，但免疫增强效价为250,000。C组和D组分别接受这些制剂的10倍稀释液。对所有实验组猴子在免疫后第68天采集的外周血单个核白细胞进行检测时，未发现迁移抑制因子。将接种疫苗后第1天至第12天采集的血清接种到成年白纹伊蚊和LLC-MK2细胞中，未在任何猴子中检测到病毒血症。到第89天，A、B和C组的六只猴子中有四只通过中和试验血清阳转，D组的五只猴子中有三只（一只猴子在麻醉后死于心脏衰竭）血清阳转。已知在循环异源黄病毒抗体的人类和猴子中会发生登革热病毒感染的免疫增强。在本研究中，当抗体与2型登革热疫苗病毒混合并皮下注射时，没有增强作用。
