Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity
Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity
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DOI：
10.1073/pnas.0403492101
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发表时间：
2004-06-29
影响因子：
11.1
通讯作者：
Collins, PL
中科院分区：
文献类型：
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作者：
Buchholz, UJ;Bukreyev, A;Collins, PL
我们研究了严重急性呼吸综合征（SARS）冠状病毒（CoV）的结构蛋白的保护性免疫的贡献，通过表达它们单独和组合从重组副流感病毒（PIV）3型载体称为BHPIV 3。这种载体提供了对呼吸道的直接免疫，呼吸道是SARS传播、复制和疾病的主要场所。在仓鼠中评价BHPIV 3/SARS重组体的免疫原性和保护效力，这支持肺SARS-CoV的高水平复制。表达SARS-CoV刺突蛋白（S）的BHPIV 3单次鼻内给药诱导了高滴度的SARS-CoV中和血清抗体，仅比SARS-CoV感染诱导的抗体低2倍。S与另外两种推定的病毒体包膜蛋白（基质M和小包膜E蛋白）的表达没有增强中和抗体应答。在缺乏5的情况下，M和E或核衣壳蛋白N的表达没有诱导可检测的血清SARS-CoV中和抗体应答。用表达S的BHPIV 3免疫在下呼吸道中提供了对SARS-CoV攻击的完全保护，在上呼吸道中提供了部分保护。与M和E的共表达使其略微增强。在不存在S的情况下，M、E或N的表达没有提供可检测的保护。这些结果鉴定了结构蛋白中的S作为唯一重要的SARS-CoV中和抗原和保护性抗原，并表明在支持SARS-CoV有效复制的实验动物中，单一粘膜免疫具有高度保护性。
We investigated the contributions of the structural proteins of severe acute respiratory syndrome (SARS) coronavirus (CoV) to protective immunity by expressing them individually and in combinations from a recombinant parainfluenza virus (PIV) type 3 vector called BHPIV3. This vector provided direct immunization of the respiratory tract, the major site of SARS transmission, replication, and disease. The BHPIV3/SARS recombinants were evaluated for immunogenicity and protective efficacy in hamsters, which support a high level of pulmonary SARS-CoV replication. A single intranasal administration of BHPIV3 expressing the SARS-CoV spike protein (S) induced a high titer of SARS-CoV-neutralizing serum antibodies, only 2-fold less than that induced by SARS-CoV infection. The expression of S with the two other putative virion envelope proteins, the matrix M and small envelope E proteins, did not augment the neutralizing antibody response. In absence of 5, expression of M and E or the nucleocapsid protein N did not induce a detectable serum SARS-CoV-neutralizing antibody response. Immunization with BHPIV3 expressing S provided complete protection against SARS-CoV challenge in the lower respiratory tract and partial protection in the upper respiratory tract. This was augmented slightly by coexpression with M and E. Expression of M, E, or N in the absence of S did not confer detectable protection. These results identify S among the structural proteins as the only significant SARS-CoV neutralization antigen and protective antigen and show that a single mucosal immunization is highly protective in an experimental animal that supports efficient replication of SARS-CoV.