Immunization of primates with a newcastle disease virus-vectored vaccine via the respiratory tract induces a high titer of serum neutralizing antibodies against highly pathogenic avian influenza virus
Immunization of primates with a newcastle disease virus-vectored vaccine via the respiratory tract induces a high titer of serum neutralizing antibodies against highly pathogenic avian influenza virus
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DOI：
10.1128/jvi.00713-07
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发表时间：
2007-11-01
影响因子：
5.4
通讯作者：
Bukreyev, Alexander
中科院分区：
文献类型：
--
作者：
DiNapoli, Joshua M.;Yang, Lijuan;Bukreyev, Alexander
高致病性禽流感病毒（HPAIV）在鸟类中的持续爆发、导致高死亡率的传播给人类的发生率以及人类大流行的可能性保证了针对HPAIV的有效人用疫苗的开发。本研究以表达H5 N1亚型高致病性禽流感病毒（HPAIV）血凝素（HA）糖蛋白的重组禽纽卡斯尔病病毒（NDV）为基础，研制了一种呼吸道直接接种的实验性弱毒活疫苗（NDV-HA）。HPAIV HA基因的表达轻微降低了NDV的毒力，如通过增加的平均胚胎死亡时间和减少的鸡复制所证明的。将NDV-RA分两次给予非洲绿色猴，每次2 × 10（7）感染单位，间隔28天，以评价H5 N1 HPAIV特异性的全身和局部抗体应答。该病毒仅以低滴度从猴子身上脱落，表明安全性。两种剂量的NDV-HA在所有免疫猴中诱导高滴度的H5 N1 HPAIV中和血清抗体。此外，在一次和两次给药后，在呼吸道中诱导了大量粘膜免疫球蛋白A应答。本研究中获得的中和抗体滴度表明，该疫苗可能预防H5 N1 HPAIV引起的死亡并降低发病率。此外，在呼吸道中诱导局部免疫应答是一个重要的优势，可能会在爆发或大流行期间减少或预防病毒的传播。该疫苗是人类临床评价的候选疫苗。
The ongoing outbreak of highly pathogenic avian influenza virus (HPAIV in birds, the incidence of transmission to humans with a resulting high mortality rate, and the possibility of a human pandemic warrant the development of effective human vaccines against HPAIV. We developed an experimental live-attenuated vaccine for direct inoculation of the respiratory tract based on recombinant avian Newcastle disease virus (NDV) expressing the hemagglutinin (HA) glycoprotein of H5N1 HPAIV (NDV-HA). Expression of the HPAIV HA gene slightly reduced NDV virulence, as evidenced by the increased mean embryo death time and reduced replication in chickens. NDV-RA was administered to African green monkeys in two doses of 2 x 10(7) infectious units each with a 28-day interval to evaluate the systemic and local antibody responses specific to H5N1 HPAIV. The virus was shed only at low titers from the monkeys, indicative of safety. Two doses of NDV-HA induced a high titer of H5N1 HPAIV-neutralizing serum antibodies in all of the immunized monkeys. Moreover, a substantial mucosal immunoglobulin A response was induced in the respiratory tract after one and two doses. The titers of neutralizing antibodies achieved in this study suggest that the vaccine would be likely to prevent mortality and reduce morbidity caused by the H5N1 HPAIV. In addition, induction of a local immune response in the respiratory tract is an important advantage that is likely to reduce or prevent transmission of the virus during an outbreak or a pandemic. This vaccine is a candidate for clinical evaluation in humans.