Vaccination with self-adjuvanted protein nanoparticles provides protection against lethal influenza challenge

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• 作者：Christopher P. Karch ; PhD^a ; ¹ ; Jianping Li^b ; ¹ ; Caroline Kulangara ; PhD^c ; ¹ ; Sara M. Paulillo ; PhD^c ; Senthil K. Raman ; PhD^c ; Sharareh Emadi ; PhD^d ; Anmin Tan ; PhD^d ; Zeinab H. Helal ; PhD^b ; ^e ; Qing Fan ; PhD^b ; ^f ; Mazhar I. Khan ; PhD^b ; ^{mazhar.khan@uconn.edu} ; Peter Burkhard ; PhD^a ; ^c ; ^d ; ^{peter.burkhard@uconn.edu}
• 关键词：Nanoparticle ; Influenza ; Vaccine ; M2e ; Flagellin
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：13
• 期：1
• 页码：241-251
• 全文大小：1682 K
• 卷排序：13

文摘

Current influenza vaccines should be improved by the addition of universal influenza vaccine antigens in order to protect against multiple virus strains. We used our self-assembling protein nanoparticles (SAPNs) to display the two conserved influenza antigens M2e and Helix C in their native oligomerization states. To further improve the immunogenicity of the SAPNs, we designed and incorporated the TLR5 agonist flagellin into the SAPNs to generate self-adjuvanted SAPNs. We demonstrate that addition of flagellin does not affect the ability of SAPNs to self-assemble and that they are able to stimulate TLR5 in a dose-dependent manner. Chickens vaccinated with the self-adjuvanted SAPNs induce significantly higher levels of antibodies than those with unadjuvanted SAPNs and show higher cross-neutralizing activity compared to a commercial inactivated virus vaccine. Upon immunization with self-adjuvanted SAPNs, mice were completely protected against a lethal challenge. Thus, we have generated a self-adjuvanted SAPN with a great potential as a universal influenza vaccine.