Immunization of monkeys with baculovirus-dengue type-4 recombinants containing envelope and nonstructural proteins: evidence of priming and partial protection.

Immunization of monkeys with baculovirus-dengue type-4 recombinants containing envelope and nonstructural proteins: evidence of priming and partial protection.
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用含有包膜蛋白和非结构蛋白的杆状病毒-登革热 4 型重组体对猴子进行免疫:启动和部分保护的证据。

DOI:
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发表时间:
1994
影响因子:
3.3
通讯作者:
Ching
Ching
中科院分区:
医学4区
文献类型:
--
作者:
K. Eckels;Mark Shelly;P. Summers;Sara B. Cohen;J. Schlesinger;S. Hasty;D. Dubois;I. Kurane;Billy Howard;Allan Rothman;Yi;Ching

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用登革4型杆状病毒(DEN-4)重组感染细胞提取液免疫恒河猴。另一种重组蛋白含有部分呼吸道合胞病毒G糖蛋白和DEN-4包膜糖蛋白(RSVG-E)。这两种制剂都是免疫原性的;在酶免疫分析中,所有接受其中一种免疫原的猴子都会产生抗病毒抗体。除了一只接受重组b(C-M-E-NS1-NS2a)的猴子外,所有猴子都产生了NS1抗体。一只接受b(RSVG-E)的猴子表现出低水平的中和抗体产生。在用未修饰的DEN-4病毒攻击后,免疫组的9只猴子中有7只被感染,平均病毒存活时间为4.1d。对照组、假接种组的猴子也是病毒携带者;该组猴子病毒血症的平均天数为4.7天。免疫组中的其余猴子(n=7),虽然没有受到保护,但有启动的证据。攻击后的血凝抑制抗体反应表明在这组动物中有记忆反应。根据这些结果,得出的结论是,未来的免疫计划应该改变,以优化免疫反应,用更有效和更纯化的免疫原免疫可能会导致更高的血清转换率和猴子的抗体水平。
Groups of rhesus monkeys were immunized with baculovirus-dengue type-4 (DEN-4) recombinant-infected cell extracts. One recombinant contained all of the DEN-4 structural proteins and two nonstructural (NS) proteins (C-M-E-NS1-NS2a), while the other was a fusion protein containing a portion of the respiratory syncytial virus G glycoprotein and DEN-4 envelope glycoprotein (RSVG-E). Both preparations were immunogenic; all monkeys receiving either immunogen responded with the production of antivirion antibodies in enzyme immunoassays. All except one monkey receiving the recombinant b(C-M-E-NS1-NS2a) made antibodies to NS1. One monkey that received b(RSVG-E) showed the production of low levels of neutralizing antibodies. Following challenge with unmodified DEN-4 virus, seven of nine monkeys in the immunized group became infected and were viremic for a mean of 4.1 days. The control, sham-inoculated monkeys were also viremic; the mean number of days of viremia in this group was 4.7 days. The remaining monkeys in the immunized group (n = 7), although not protected, had evidence of priming. Hemagglutination inhibition antibody responses following challenge indicated an anamnestic response in this group of animals. Based on these results, it was concluded that future immunization schedules should be altered to optimize immune responses and that immunization with more potent and purified immunogens would probably result in higher seroconversion rates and antibody levels in monkeys.