Respiratory tract immunization of non-human primates with a Newcastle disease virus-vectored vaccine candidate against Ebola virus elicits a neutralizing antibody response.

Respiratory tract immunization of non-human primates with a Newcastle disease virus-vectored vaccine candidate against Ebola virus elicits a neutralizing antibody response.
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DOI:
10.1016/j.vaccine.2010.10.024
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发表时间:
2010-12-10
期刊:
影响因子:
5.5
通讯作者:
Bukreyev, Alexander
Bukreyev, Alexander
中科院分区:
医学3区
文献类型:
--
作者:
DiNapoli, Joshua M.;Yang, Lijuan;Samal, Siba K.;Murphy, Brian R.;Collins, Peter L.;Bukreyev, Alexander

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我们之前开发了一种基于人副流感病毒3型(HPIV3)的呼吸道疫苗候选,该病毒是一种呼吸道副粘病毒,表达EBOV GP外膜蛋白(HPIV3/GP)。这种疫苗候选疫苗通过鼻腔和气管内途径提供两剂疫苗,保护猴子免受EBOV的腹膜攻击;然而,有人担心,由于先前存在对HPIV3的免疫,候选疫苗可能降低了成年人群的免疫原性。在这里,我们开发了一种基于新城疫病毒(NDV)的新的候选疫苗(NDV/GP)。新城疫病毒是一种禽类副粘病毒,在抗原性上与人类病毒病原体不同,在猴子身上高度减毒。鼻腔和气管内接种新城疫病毒/糖蛋白后,呼吸道分泌物和血清标本中EBOV特异性抗体的效价以及血清中和抗体的效价均低于HPIV3/GP疫苗。第二次免疫后血清中的抗体效价显著提高,但仍低于第二次HPIV3/GP免疫后的滴度。相反,呼吸道分泌物中的EBOV中和抗体效价与第二剂HPIV3/GP免疫后的效价相当。这些数据表明,新城疫病毒/gp可单独用于EBOV免疫,或与HPIV3/gp或其他疫苗平台在异种Prime-Boost方案中联合使用。
We previously developed a respiratory tract vaccine candidate against Ebola virus (EBOV) based on human parainfluenza virus type 3 (HPIV3), a respiratory paramyxovirus, expressing the EBOV GP envelope protein (HPIV3/GP) from an added gene. Two doses of this vaccine candidate delivered by the intranasal and intratracheal route protected monkeys against intraperitoneal challenge with EBOV; however, concerns exist that the vaccine candidate may have reduced immunogenicity in the adult human population due to pre-existing immunity against HPIV3. Here we developed a new vaccine candidate (NDV/GP) based on Newcastle disease virus (NDV), an avian paramyxovirus that is antigenically distinct from human viral pathogens and is highly attenuated in monkeys. Following one intranasal and intratracheal inoculation of Rhesus monkeys with NDV/GP, titers of EBOV-specific antibodies in respiratory tract secretions and serum samples determined by ELISA, as well as serum EBOV-neutralizing antibodies, were undetectable or low compared to those induced by HPIV3/GP. A second immunization resulted in a substantial boost in serum IgG ELISA titers, yet the titers remained lower than those induced by a second dose of HPIV3/GP. In contrast, the ELISA IgA titers in respiratory tract secretions and, more importantly, the serum EBOV-neutralizing antibody titers were equal to those induced after the second dose of HPIV3/GP. These data suggest that NDV/GP can be effective for immunization against EBOV alone, or in combination with either HPIV3/GP or another vaccine platform in a heterologous prime-boost regimen.
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