流感universal vaccine design (monoglycosylated hemagglutinin)

Vaccination of monoglycosylated hemagglutinin induces cross-strain protection against influenza virus infections (pnas.1323954111) The 2009 H1N1 pandemic and recent human cases of H5N1, H7N9, and H6N1 in Asia highlight the need for a universal influenza vaccine that can provide cross-strain or even cross-subtype protection. Here, we show that recombinant monoglycosylated hemagglutinin (HAmg) with an intact protein structure from either seasonal or pandemic H1N1 can be used as a vaccine for cross-strain protection against various H1N1 viruses in circulation from 1933 to 2009 in mice and ferrets. In the HAmg vaccine, highly conserved sequences that were originally covered by glycans in the fully glycosylated HA (HAfg) are exposed and thus, are better engulfed by dendritic cells (DCs), stimulated better DC maturation, and induced more CD8+ memory T cells and IgG-secreting plasma cells. Single B-cell RT-PCR followed by sequence analysis revealed that the HAmg vaccine activated more diverse B-cell repertoires than the HAfg vaccine and produced antibodies with cross-strain binding ability. In summary, the HAmg vaccine elicits cross-strain immune responses that may mitigate the current need for yearly reformulation of strain-specific inactivated vaccines. This strategy may also map a new direction for universal vaccine design.

醣蛋白助益 流感疫苗功效提升 2014/01/28 11:26:29 （中央社記者許秩維台北2014年1月28日電）中研院團隊以醣蛋白為基礎，重新設計流感疫苗，證實創新疫苗可啟動生物免疫力功效，對抗多種病毒株，研究登國際期刊首頁。中央研究院長翁啟惠和基因體研究中心副研究員馬徹、林國儀所領導的研究團隊，利用醣蛋白的穩定性特色，創新設計出帶有單醣的血凝素疫苗，同時結合不同長度的醣，設計多種流感疫苗，研究結果刊登在國際頂尖期刊「美國國家科學院學報」網路版首頁。根據世界衛生組織統計，每年約有50萬病患因流感致死，注射流感疫苗是目前最佳的預防方式，但流感病毒種類多、病毒突變快速，世界衛生組織每年必須預測下一季可能盛行的病毒株種類並加以設計疫苗，若預測失準，就可能發生如H1N1流感病毒大流行的嚴重疫情。研究團隊指出，近年亞洲地區頻繁發生H5N1、H7N9、H6N1等流感病毒疫情，顯示迫切需要新型態的流感疫苗，以達到更具預防長效且無需每年施打的防疫目標；而團隊利用醣蛋白的穩定性特色，設計帶有單醣的血凝素疫苗，由血凝素扮演抗原角色，啟動更有效的抗體。研究團隊表示，將血凝素與不同長度的醣結合，進而設計出多種流感疫苗，經注射到小鼠和雪貂體內，發現較傳統的多醣疫苗，單醣疫苗誘發免疫力的效果更佳，同時對其它3種不同流感病毒株更具保護作用，顯示以單醣結合血凝素所設計出的流感疫苗，更具對抗不同種類流感病毒株的功效，提供未來疫苗設計的新方向。