一种针对黄热病的灭活细胞培养疫苗。

An inactivated cell-culture vaccine against yellow fever.

机构信息

Xcellerex, Marlborough, MA, USA.

出版信息

N Engl J Med. 2011 Apr 7;364(14):1326-33. doi: 10.1056/NEJMoa1009303.

DOI:10.1056/NEJMoa1009303

PMID:21470010

Abstract

BACKGROUND

Yellow fever is a lethal viral hemorrhagic fever occurring in Africa and South America. A highly effective live vaccine (17D) is widely used for travelers to and residents of areas in which yellow fever is endemic, but the vaccine can cause serious adverse events, including viscerotropic disease, which is associated with a high rate of death. A safer, nonreplicating vaccine is needed.

METHODS

In a double-blind, placebo-controlled, dose-escalation, phase 1 study of 60 healthy subjects between 18 and 49 years of age, we investigated the safety and immunogenicity of XRX-001 purified whole-virus, β-propiolactone-inactivated yellow fever vaccine produced in Vero cell cultures and adsorbed to aluminum hydroxide (alum) adjuvant. On two visits 21 days apart, subjects received intramuscular injections of vaccine that contained 0.48 μg or 4.8 μg of antigen. Levels of neutralizing antibodies were measured at baseline and on days 21, 31, and 42.

RESULTS

The vaccine induced the development of neutralizing antibodies in 100% of subjects receiving 4.8 μg of antigen in each injection and in 88% of subjects receiving 0.48 μg of antigen in each injection. Antibody levels increased by day 10 after the second injection, at which time levels were significantly higher with the 4.8-μg formulation than with the 0.48-μg formulation (geometric mean titer, 146 vs. 39; P<0.001). Three adverse events occurred at a higher incidence in the two vaccine groups than in the placebo group: mild pain, tenderness, and (much less frequently) itching at the injection site. One case of urticaria was observed on day 3 after the second dose of 4.8 μg of vaccine.

CONCLUSIONS

A two-dose regimen of the XRX-001 vaccine, containing inactivated yellow fever antigen with an alum adjuvant, induced neutralizing antibodies in a high percentage of subjects. XRX-001 has the potential to be a safer alternative to live attenuated 17D vaccine. (Funded by Xcellerex; ClinicalTrials.gov number, NCT00995865.).

摘要

背景

黄热病是一种致命的病毒性出血热，发生在非洲和南美洲。一种高度有效的活疫苗（17D）被广泛用于前往黄热病流行地区的旅行者和居民，但该疫苗会引起严重的不良反应，包括内脏病变，这与高死亡率相关。因此，需要一种更安全、非复制的疫苗。

方法

在一项针对 60 名年龄在 18 至 49 岁之间的健康受试者的双盲、安慰剂对照、剂量递增、1 期研究中，我们研究了 XRX-001 纯化全病毒、β-丙内酯灭活的黄热病疫苗在 Vero 细胞培养物中生产，并与氢氧化铝（铝佐剂）吸附的安全性和免疫原性。在两次间隔 21 天的就诊中，受试者接受了肌肉内注射疫苗，疫苗中含有 0.48μg 或 4.8μg 的抗原。在基线和第 21、31 和 42 天测量中和抗体水平。

结果

接受每剂 4.8μg 抗原的受试者中，有 100%产生了中和抗体，接受每剂 0.48μg 抗原的受试者中，有 88%产生了中和抗体。第二次注射后 10 天，抗体水平开始升高，此时 4.8μg 制剂组的抗体水平明显高于 0.48μg 制剂组（几何平均滴度，146 比 39；P<0.001）。与安慰剂组相比，两种疫苗组中发生的不良反应发生率更高：注射部位出现轻度疼痛、压痛和（更少见）瘙痒。在第二次接种 4.8μg 疫苗后第 3 天观察到 1 例荨麻疹。