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作者：Bob Roehr  
出處：WebMD醫學新聞

　　May 5, 2010 (馬里蘭州貝什斯達) — 根據發表於國家感染症基金會第13屆疫苗研究年會的初步研究，三價流感疫苗(TIV)併用融合蛋白可以增加具保護性抗體的效價達50%。
　　
　　田納西州那什維爾Vanderbilt大學醫學中心的H. Keipp Talbot醫師在發表時指出，目前的疫苗在年長者產生高效價抗體的效率較低。
　　
　　Talbot醫師獲得Maurice R. Hilleman早期生涯研究獎，包括10,000美元的研究資助，用於他和同事們進行的促進流感疫苗研究。
　　
　　VAX102是一個新的疫苗，融合了通過流感保留的M2e膜蛋白，到一個「類鐸受體5 (toll-like receptor [TLR]5)」配位體，在此案例是沙門氏鼠傷寒桿菌鞭毛蛋白。
　　
　　Talbot醫師解釋，目標是升高抗體效價且加強它們的反應，以讓它們對未包括在TIV內的流感變化有一些交叉保護力，在動物模式中，它可對抗流感挑戰並促進對標準TIV的反應。
　　
　　這個多中心雙盲隨機控制第1期試驗包括了80名年紀18-49歲的研究對象，他們接受TIV加安慰劑或者TIV加VAX102。
　　
　　研究終點是第14天和第28天的血球凝集抑制(HI)效價，且用ELISA評估M2e和鞭毛蛋白，研究強度足以評估安全性和產生免疫性的反應，但是在效力方面沒有獲得結論。
　　
　　Talbot醫師表示，這些疫苗注射耐受良好，VAX102組只有注射部位疼痛略為增加，但是沒有嚴重不良反應，VAX102組對H1和H3的反應也比安慰劑高(約1.5倍高)，但是這些差異並未達統計上的顯著意義。
　　
　　Aventis Pasteur MSD退休醫療主任David S. Fedson醫師形容這是個引人注意的初步研究，重點之一、尚待解答的問題是，產生的反應是否對未包括在TIV的病毒有交叉反應。
　　
　　後續在與Medscape Infectious Diseases的訪談中，Talbot醫師表示，美國食品藥物管理局(FDA)採用的核准標準是HI抗體效價達1:40以上，我們知道這對年輕健康族群的意義，但是不確定對年長者的意義，我們不知道怎樣的免疫反應代表你獲得保護。
　　
　　她指出，單以實際年齡未能絕對地預測反應，還有一個缺陷因素，你的免疫年齡可能大於你的實際年齡。
　　
　　該研究只有測量注射疫苗後14天和28天時的效價，這也是FDA使用的指標，它並未評估更後期的效價來判斷融合蛋白是否影響抗體效價之持續性，也未評估兩組產生之抗體的效力或作用。
　　
　　Vanderbilt大學和VaxInnate公司(發展TLR-導向之季節性流感疫苗的私人公司)資助該研究，研究者皆宣告沒有相關財務關係。
　　
　　國家感染症基金會(NFID)第13屆疫苗研究年會：摘要P10，發表於2010年4月27日。  


Fusion Protein May Enhance Efficacy of Influenza Vaccine

By Bob Roehr
Medscape Medical News

May 5, 2010 (Bethesda, Maryland) — Coadministration of a fusion protein with trivalent influenza vaccine (TIV) might increase titers of protective antibody by 50%, according to preliminary research presented here at the National Foundation for Infectious Diseases 13th Annual Conference on Vaccine Research.

Current vaccines are less effective at generating high titers of antibody in older people, noted presenter H. Keipp Talbot, MD, from Vanderbilt University Medical Center in Nashville, Tennessee.

Dr. Talbot garnered the Maurice R. Hilleman Early-Stage Career Investigator Award, which includes $10,000 in research support, for research he and his colleagues conducted on an enhanced influenza vaccine.

VAX102 is a novel vaccine that fuses the M2e membrane protein, conserved across influenza, to a toll-like receptor (TLR)5 ligand, in this case Salmonella typhimurium flagellin.

The goal is to heighten antibody titers and to broaden their response so that they provide some cross-protection to variants of influenza not included in the TIV, Dr. Talbot explained. In animal models, it protects against influenza challenge and enhances response to standard TIV.

The multicenter double-blind, randomized controlled phase?1 trial involved 80 participants 18 to 49 years of age. They received either TIV plus placebo or TIV plus VAX102.

End points were day 14 and day 28 hemagglutination inhibition (HI) titers, and M2e and flagellin as assessed by ELISA. The study was powered to evaluate safety and reactive immunogenicity, but not to reach conclusions about efficacy.

Dr. Talbot said the vaccinations were well tolerated, with modest increased injection-site pain associated with VAX102, but no serious adverse events. The VAX102 group did generate higher levels of response (approximately 1.5 times higher) to H1 and H3 than placebo, but the difference did not reach statistical significance.

David S. Fedson, MD, retired medical director of Aventis Pasteur MSD, called the study intriguing but very preliminary. One important and still-unanswered question is whether the response generated has any cross-reactive effect on virus not included in the TIV.

In a subsequent conversation with Medscape Infectious Diseases, Dr. Talbot said that the US Food and Drug Admnistration (FDA) uses HI antibody titers of 1:40 or higher for the purposes of licensure. "We know what that means in young healthy adults. We're not sure what that means in older adults. We don't know what immune response means you're protected."

She pointed out that chronological age alone is not an absolute predictor of response. "There is a frailty factor, as well. Your immune age may be older than your chronologic age."

The study only measured titers at postvaccination days 14 and 28, mileposts used by the FDA. It did not evaluate titers at a later time point to see if the fusion protein affected the persistence of antibody titers, nor has it evaluated the efficiency or functionality of the antibody generated in both groups.

The study was funded by Vanderbilt University and VaxInnate Corp., a privately held company developing TLR-oriented seasonal influenza vaccines. The researchers have disclosed no relevant financial relationships.

National Foundation for Infectious Diseases (NFID) 13th Annual Conference on Vaccine Research: Abstract?P10. Presented April?27, 2010