Recombinant bovine/human parainfluenza virus type 3 (B/HPIV3) expressing the respiratory syncytial virus (RSV) G and F proteins can be used to achieve simultaneous mucosal immunization against RSV and HPIV3
Recombinant bovine/human parainfluenza virus type 3 (B/HPIV3) expressing the respiratory syncytial virus (RSV) G and F proteins can be used to achieve simultaneous mucosal immunization against RSV and HPIV3
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DOI：
10.1128/jvi.75.10.4594-4603.2001
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发表时间：
2001-05-01
影响因子：
5.4
通讯作者：
Collins, PL
中科院分区：
文献类型：
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作者：
Schmidt, AC;McAuliffe, JM;Collins, PL
重组牛/人副流感病毒3型利用重组牛病毒3型（rB/HPIV 3）表达呼吸道合胞病毒（RSV）的主要保护性抗原，以构建抗RSV和HPIV 3的双价粘膜疫苗，rB/HPIV 3的减毒由灵长类动物中BPIV 3骨架的宿主范围限制提供。将RSV G和F开放阅读框（ORF）置于PIV 3转录信号的控制下，并分别插入rB/HPIV 3基因组中启动子近端位置的核衣壳蛋白基因之前。表达RSV G ORF的重组PIV 3（rB/HPIV 3-G1）在体外复制不受限制，而表达RSV F ORF的病毒（rB/HPIV 3-F1）与其rB/HPIV 3亲本相比受到8倍限制。两种病毒在仓鼠的呼吸道中有效复制，并且每种病毒诱导的RSV血清抗体滴度与RSV感染诱导的相似，抗HPIV 3滴度与HPIV 3感染诱导的相似。用rB/HPIV 3-G1、rB/HPIV 3-F1或两种病毒的组合免疫仓鼠，28天后对RSV或HPIV 3攻毒产生高水平抗性。这些结果描述了一种疫苗策略，其避免了与减毒活RSV疫苗相关的技术挑战，提供了针对儿科呼吸道疾病的两种主要病毒因子的二价疫苗，其减毒表型基于BPIV 3的广泛宿主范围序列差异。
Recombinant bovine/human parainfluenza virus type 3 (rB/HPIV3), a recombinant bovine PIV3 (rBPIV3) in which the F and HN genes were replaced with their HPIV3 counterparts, was used to express the major protective antigens of respiratory syncytial virus (RSV) in order to create a bivalent mucosal vaccine against RSV and HPIV3, The attenuation of rB/HPIV3 is provided by the host range restriction of the BPIV3 backbone in primates. RSV G and F open reading frames (ORFs) were placed under the control of PIV3 transcription signals and inserted individually into the rB/HPIV3 genome in the promoter-proximal position preceding the nucleocapsid protein gene. The recombinant PIV3 expressing the RSV G ORF (rB/HPIV3-G1) was not restricted in its replication in vitro, whereas the virus expressing the RSV F ORF (rB/HPIV3-F1) was eightfold restricted compared to its rB/HPIV3 parent. Both viruses replicated efficiently in the respiratory tract of hamsters, and each induced RSV serum antibody titers similar to those induced by RSV infection and anti-HPIV3 titers similar to those induced by HPIV3 infection. Immunization of hamsters with rB/HPIV3-G1, rB/HPIV3-F1, or a combination of both viruses resulted in a high level of resistance to challenge with RSV or HPIV3 28 days later. These results describe a vaccine strategy that obviates the technical challenges associated with a live attenuated RSV vaccine, providing, against the two leading viral agents of pediatric respiratory tract disease, a bivalent vaccine whose attenuation phenotype is based on the extensive host range sequence differences of BPIV3.