A gene deletion that up-regulates viral gene expression yields an attenuated RSV vaccine with improved antibody responses in children.
A gene deletion that up-regulates viral gene expression yields an attenuated RSV vaccine with improved antibody responses in children.
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DOI：
10.1126/scitranslmed.aac8463
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发表时间：
2015-11-04
影响因子：
17.1
通讯作者：
Buchholz UJ
中科院分区：
文献类型：
--
作者：
Karron RA;Luongo C;Thumar B;Loehr KM;Englund JA;Collins PL;Buchholz UJ
呼吸道合胞病毒（RSV）是导致儿童严重呼吸道疾病的主要病毒，因此需要一种安全有效的婴幼儿疫苗。我们之前的研究表明，病毒M2-2蛋白（ΔM2-2）编码序列的缺失下调了病毒RNA复制，上调了基因转录和抗原合成，从而提高了开发具有增强免疫原性的减毒疫苗的可能性。因此，RSV MEDI ΔM2-2被评估为成人、RSV血清阳性儿童和RSV血清阴性儿童的鼻内活疫苗。当将RSV血清阴性儿童的结果与先前主要的RSV减毒候选活疫苗的结果进行比较时，疫苗病毒脱落明显受到更大的限制，但接种后获得的RSV中和血清抗体[几何平均滴度(GMT) = 1:97]显着更高。在随后的RSV季节监测显示，一些血清阴性的RSV MEDI ΔM2-2受体有明显的抗体上升，但没有报告疾病，这表明该疫苗具有保护作用，但为RSV的遗忘反应做好了准备。合理的设计似乎已经产生了一种候选RSV疫苗，它在RSV-nai儿童中具有内在优势，并突出了开发RSV减毒活疫苗的方法。
Respiratory syncytial virus (RSV) is the leading viral cause of severe pediatric respiratory illness, and a safe and effective vaccine for use in infancy and early childhood is needed. We previously showed that deletion of the coding sequence for the viral M2–2 protein (ΔM2–2) down-regulated viral RNA replication and up-regulated gene transcription and antigen synthesis, raising the possibility of development of an attenuated vaccine with enhanced immunogenicity. RSV MEDI ΔM2–2 was therefore evaluated as a live intranasal vaccine in adults, RSV-seropositive children, and RSV-seronegative children. When results in RSV-seronegative children were compared to those achieved with the previous leading live attenuated RSV candidate vaccine, vaccine virus shedding was significantly more restricted, yet the post-vaccination RSV-neutralizing serum antibody achieved [geometric mean titer (GMT) = 1:97] was significantly greater. Surveillance during the subsequent RSV season showed that several seronegative RSV MEDI ΔM2–2 recipients had substantial antibody rises without reported illness, suggesting that the vaccine was protective yet primed for anamnestic responses to RSV. Rational design appears to have yielded a candidate RSV vaccine that is intrinsically superior at eliciting protective antibody in RSV-nai’ve children and highlights an approach for the development of live attenuated RSV vaccines.
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影响因子：
5.5
作者：
Englund, Janet A.;Karron, Ruth A.;Schmidt, Alexander C.
通讯作者：
Schmidt, Alexander C.
影响因子：
3.7
作者：
Malkin E;Yogev R;Abughali N;Sliman J;Wang CK;Zuo F;Yang CF;Eickhoff M;Esser MT;Tang RS;Dubovsky F
通讯作者：
Dubovsky F
DOI：
10.1056/nejmoa0804877
发表时间：
2009-02-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hall CB;Weinberg GA;Iwane MK;Blumkin AK;Edwards KM;Staat MA;Auinger P;Griffin MR;Poehling KA;Erdman D;Grijalva CG;Zhu Y;Szilagyi P
通讯作者：
Szilagyi P
影响因子：
5.5
作者：
Wright, Peter F.;Karron, Ruth A.;Murphy, Brian R.
通讯作者：
Murphy, Brian R.
影响因子：
3.7
作者：
Jin, H;Zhou, H;Nguyen, N
通讯作者：
Nguyen, N