Influence of antigen insertion site and vector dose on immunogenicity and protective capacity in Sendai virus-based human parainfluenza virus type 3 vaccines.
Influence of antigen insertion site and vector dose on immunogenicity and protective capacity in Sendai virus-based human parainfluenza virus type 3 vaccines.
复制标题
抗原插入位点和载体剂量对基于仙台病毒的人副流感病毒3型疫苗免疫原性和保护能力的影响。
DOI：
10.1128/jvi.00227-13
复制
发表时间：
2013
影响因子：
5.4
通讯作者：
Russell,CharlesJ
中科院分区：
文献类型：
--
作者：
Mason,JohnN;Elbahesh,Husni;Russell,CharlesJ
用重组仙台病毒（rSeV）作为人副流感病毒3型（HPIV3）减毒活疫苗的鼻内接种和血凝素-神经氨酸酶（HN）表面糖蛋白的粘膜表达。构建了两种候选疫苗rSeV- hpiv3hn （P-M）和rSeV-HPIV3(F-HN)，分别在rSeV的P-M和F-HN基因连接中插入HPIV3HN开放阅读框和一个额外的基因连接。在LLC-MK2细胞中，与rSeV-HPIV3（F-HN）相比，rSeV-HPIV3HN（P-M）病毒被减毒，但两种候选疫苗在NHBE细胞和棉大鼠呼吸道中的生长程度相似。这些结果表明，与LLC-MK2细胞的生长相比，NHBE细胞中的蛋白载体生长更准确地预测棉花大鼠的病毒产量。这两种疫苗载体都能激发高水平的血清中和抗体，并对棉花大鼠的HPIV3攻击提供保护。与高剂量（2,000,000 PFU）疫苗接种相比，低剂量（200 PFU）鼻内接种导致鼻腔和气管中的载体生长减少10倍，肺部减少50倍。然而，低剂量疫苗接种仅导致血清中抗HPIV3抗体的适度下降，足以提供完全保护，免受HPIV3的攻击。改变HPIV3抗原插入位点和载体剂量可以对基于rsv的疫苗的体内生长和免疫原性进行微调，但测试的所有四种疫苗接种策略都能完全保护人们免受HPIV3病毒的攻击。这些结果突出了rSeV平台在开发鼻内给药呼吸道病毒疫苗方面的多功能性。
Recombinant Sendai virus (rSeV) was used as a live, attenuated vaccine vector for intranasal inoculation and mucosal expression of the hemagglutinin-neuraminidase (HN) surface glycoprotein of human parainfluenza virus type 3 (HPIV3). Two vaccine candidates rSeV-HPIV3HN(P-M) and rSeV-HPIV3(F-HN) were constructed in which the HPIV3 HN open reading frame and an additional gene junction was inserted in the P-M and F-HN gene junctions of rSeV, respectively. The rSeV-HPIV3HN(P-M) virus was attenuated compared to rSeV-HPIV3(F-HN) in LLC-MK2 cells, and yet both vaccine candidates grew to similar extents in NHBE cells and in the respiratory tracts of cotton rats. These results suggest thatin vitrovector growth in NHBE cells more accurately predicts virus yield in cotton rats than does growth in LLC-MK2 cells. Both vaccine vectors elicited high levels of serum neutralizing antibodies and conferred protection from HPIV3 challenge in cotton rats. Compared to vaccination with a high dose (2,000,000 PFU), intranasal inoculation with a low dose (200 PFU) resulted in a 10-fold decrease in vector growth in the nasal cavity and trachea and a 50-fold decrease in the lungs. However, low-dose vaccination resulted in only modest decreases in anti-HPIV3 antibodies in sera and was sufficient to confer complete protection from HPIV3 challenge. Varying the HPIV3 antigen insertion site and vector dose allowed fine-tuning of thein vivogrowth and immunogenicity of rSeV-based vaccines, but all four vaccination strategies tested resulted in complete protection from HPIV3 challenge. These results highlight the versatility of the rSeV platform for developing intranasally administered respiratory virus vaccines.