Gene-based neonatal immune priming potentiates a mucosal adenoviral vaccine encoding mycobacterial Ag85B.
Gene-based neonatal immune priming potentiates a mucosal adenoviral vaccine encoding mycobacterial Ag85B.
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DOI：
10.1016/j.vaccine.2016.10.065
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发表时间：
2016-12-07
期刊：
影响因子：
5.5
通讯作者：
Ramsay AJ
中科院分区：
文献类型：
--
作者：
Dai G;Rady HF;Huang W;Shellito JE;Mason C;Ramsay AJ
结核病仍然是世界范围内的一个主要公共卫生危害，新生儿和幼儿可能比成人更容易受到感染。卡介苗是目前唯一可用的疫苗，对儿童结核性脑膜炎提供了一定的保护，但对成人的疗效不一，对免疫功能低下的个体使用不安全。一种安全有效的疫苗，可以在生命早期接种，也可以加强随后的加强免疫，这将是一个重大的进步。为了测试这一命题，我们已经产生了基因为基础的疫苗载体表达Ag 85 B结核分枝杆菌（Mtb）和设计的实验，以测试其免疫原性和保护效力，特别是当在异源初免-加强组合，与初始DNA疫苗成分出生后不久。皮内递送DNA疫苗引起新生小鼠对Ag 85 B的基于Th 1的免疫应答，但不能保护它们免受随后的强毒Mtb H37 Rv气溶胶攻击。编码Ag 85 B的重组腺病毒载体，在6周龄时通过鼻内途径给予，产生中度免疫应答，保护性较差。然而，新生儿DNA引发后用重组腺病毒粘膜加强产生了强免疫应答，如肺相关淋巴结和脾中的强Ag 85 B特异性CD 4+和CD 8 + T细胞应答所证明的，通过这些应答细胞的质量（通过其分泌多种抗微生物因子的能力来评估），以及通过改善的保护，如肺TB攻击后肺中细菌负荷减少所示。这些结果表明，新生儿免疫与基因为基础的疫苗可能会创造一个有利的免疫环境，增强肺粘膜加强效果的后续异源载体疫苗编码相同的抗原。我们的数据表明，在适当的疫苗环境中，在生命早期用分枝杆菌抗原免疫可以引发针对Mtb的保护性免疫。
Tuberculosis remains a major public health hazard worldwide, with neonates and young infants potentially more susceptible to infection than adults. BCG, the only vaccine currently available, provides some protection against tuberculous meningitis in children but variable efficacy in adults, and is not safe to use in immune compromised individuals. A safe and effective vaccine that could be given early in life, and that could also potentiate subsequent booster immunization, would represent a significant advance. To test this proposition, we have generated gene-based vaccine vectors expressing Ag85B from Mycobacterium tuberculosis (Mtb) and designed experiments to test their immunogenicity and protective efficacy particularly when given in heterologous prime-boost combination, with the initial DNA vaccine component given soon after birth. Intradermal delivery of DNA vaccines elicited Th1-based immune responses against Ag85B in neonatal mice but did not protect them from subsequent aerosol challenge with virulent Mtb H37Rv. Recombinant adenovirus vectors encoding Ag85B, given via the intranasal route at six weeks of age, generated moderate immune responses and were poorly protective. However, neonatal DNA priming following by mucosal boosting with recombinant adenovirus generated strong immune responses, as evidenced by strong Ag85Bspecific CD4+ and CD8+ T cell responses, both in the lung-associated lymph nodes and the spleen, by the quality of these responding cells (assessed by their capacity to secrete multiple antimicrobial factors), and by improved protection, as indicated by reduced bacterial burden in the lungs following pulmonary TB challenge. These results suggest that neonatal immunization with gene-based vaccines may create a favorable immunological environment that potentiates the pulmonary mucosal boosting effects of a subsequent heterologous vector vaccine encoding the same antigen. Our data indicate that immunization early in life with mycobacterial antigens in an appropriate vaccine setting can prime for protective immunity against Mtb.
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影响因子：
64.8
作者：
GAMMON, G;DUNN, K;SERCARZ, EE
通讯作者：
SERCARZ, EE
影响因子：
30.5
作者：
Garg, S;Oran, A;Jacob, J
通讯作者：
Jacob, J
实验过敏性脑脊髓炎的肽特异性预防。新生儿耐受性诱导的髓磷脂碱性蛋白的主要T细胞决定因素。
影响因子：
15.3
作者：
Clayton, J P;Gammon, G M;Ando, D G;Kono, D H;Hood, L;Sercarz, E E
通讯作者：
Sercarz, E E
影响因子：
168.9
作者：
Buchbinder, Susan P.;Mehrotra, Devon V.;Duerr, Ann;Fitzgerald, Daniel W.;Mogg, Robin;Li, David;Gilbert, Peter B.;Lama, Javier R.;Marmor, Michael;del Rio, Carlos;McElrath, M. Juliana;Casimiro, Danilo R.;Gottesdiener, Keith M.;Chodakewitz, Jeffrey A.;Corey, Lawrence;Robertson, Michael N.
通讯作者：
Robertson, Michael N.
DOI：
10.1084/jem.20071371
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lee HH;Hoeman CM;Hardaway JC;Guloglu FB;Ellis JS;Jain R;Divekar R;Tartar DM;Haymaker CL;Zaghouani H
通讯作者：
Zaghouani H