生物谷報道：抗體療法的應用受到限制的部分原因是，生成完全屬于人體的單克隆抗體非常困難?，F在,，通過識別人體免疫系統(tǒng)對某種特定病原體產生反應的時間窗口，Wrammert等人研究出一種有效生成高親和力人體單克隆抗體的新方法,。在接受針對流感病毒的增強免疫接種的個體中,，血液中流感特定的IgG+抗體分泌細胞的數量在接種之后一周達到峰值，占全部外周B-細胞的大約6%,。通過在這個時間窗口內收獲B-細胞,，就有可能產生超過50個人體單克隆抗體，它們  與三個具有高親和力的目標流感病毒毒株結合在一起,。整個過程所需時間不到一個月,，要比傳統(tǒng)單克隆生成方法快得多。該方法可應用于任何已有疫苗的傳染病,。

生物谷推薦英文原文：

Nature 453, 667-671 (29 May 2008) | doi:10.1038/nature06890; Received 16 October 2007; Accepted 4 March 2008; Published online 30 April 2008

Rapid cloning of high-affinity human monoclonal antibodies against influenza virus
Jens Wrammert1,10, Kenneth Smith3,10, Joe Miller1, William A. Langley1, Kenneth Kokko2, Christian Larsen2, Nai-Ying Zheng3, Israel Mays3, Lori Garman3, Christina Helms3, Judith James4,6,7, Gillian M. Air8, J. Donald Capra5,9, Rafi Ahmed1 & Patrick C. Wilson3,6,9

Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
Emory Transplant Center and Department of Surgery, Emory University School of Medicine, Atlanta, Georgia 30322, USA
Immunobiology and Cancer Research Program, The Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA
Arthritis and Immunology Research Program, The Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA
Molecular Immunogenetics Research Program, The Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA
These authors contributed equally to this work.
Correspondence to: Patrick C. Wilson3,6,9 Correspondence and requests for materials should be addressed to P.C.W. (Email: [email protected]).

Pre-existing neutralizing antibody provides the first line of defence against pathogens in general. For influenza virus, annual vaccinations are given to maintain protective levels of antibody against the currently circulating strains. Here we report that after booster vaccination there was a rapid and robust influenza-specific IgG+ antibody-secreting plasma cell (ASC) response that peaked at approximately day 7 and accounted for up to 6% of peripheral blood B cells. These ASCs could be distinguished from influenza-specific IgG+ memory B cells that peaked 14–21 days after vaccination and averaged 1% of all B cells. Importantly, as much as 80% of ASCs purified at the peak of the response were influenza specific. This ASC response was characterized by a highly restricted B-cell receptor (BCR) repertoire that in some donors was dominated by only a few B-cell clones. This pauci-clonal response, however, showed extensive intraclonal diversification from accumulated somatic mutations. We used the immunoglobulin variable regions isolated from sorted single ASCs to produce over 50 human monoclonal antibodies (mAbs) that bound to the three influenza vaccine strains with high affinity. This strategy demonstrates that we can generate multiple high-affinity mAbs from humans within a month after vaccination. The panel of influenza-virus-specific human mAbs allowed us to address the issue of original antigenic sin (OAS): the phenomenon where the induced antibody shows higher affinity to a previously encountered influenza virus strain compared with the virus strain present in the vaccine1. However, we found that most of the influenza-virus-specific mAbs showed the highest affinity for the current vaccine strain. Thus, OAS does not seem to be a common occurrence in normal, healthy adults receiving influenza vaccination.