한빛사논문
- 조회2,249
Ruipeng Lei 1,19, Wooseob Kim 2,3,19, Huibin Lv 1,4,19, Zongjun Mou 5,19, Michael J. Scherm 6,19, Aaron J. Schmitz 2, Jackson S. Turner 2, Timothy J.C. Tan 7, Yiquan Wang 1, Wenhao O. Ouyang 1, Weiwen Liang 4, Joel Rivera-Cardona 8, Chuyun Teo 1, Claire S. Graham 1, Christopher B. Brooke 8, Rachel M. Presti 9,10,11, Chris K.P. Mok 12,13,14, Florian Krammer 6,15,16, Xinghong Dai 5, Ali H. Ellebedy 2,10,11, Nicholas C. Wu 1,7,17,18,20
1Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
2Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA
3Department of Microbiology, Korea University College of Medicine, Seoul 02841, Korea
4HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
5Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106, USA
6Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
7Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
8Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
9Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA
10Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, Saint Louis, MO 63110, USA
11The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO 63110, USA
12The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, China
13Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
14S.H. Ho Research Centre for Infectious Diseases, The Chinese University of Hong Kong, Hong Kong SAR, China
15Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
16Center for Vaccine Research and Pandemic Preparedness (C-VARPP), Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
17Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
18Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
19These authors contributed equally
20Lead contact
Corresponding authors: Chris K.P. Mok, Florian Krammer, Xinghong Dai, Ali H. Ellebedy, Nicholas C. Wu
Abstract
There is growing appreciation for neuraminidase (NA) as an influenza vaccine target; however, its antigenicity remains poorly characterized. In this study, we isolated three broadly reactive N2 antibodies from the plasmablasts of a single vaccinee, including one that cross-reacts with NAs from seasonal H3N2 strains spanning five decades. Although these three antibodies have diverse germline usages, they recognize similar epitopes that are distant from the NA active site and instead involve the highly conserved underside of NA head domain. We also showed that all three antibodies confer prophylactic and therapeutic protection in vivo, due to both Fc effector functions and NA inhibition through steric hindrance. Additionally, the contribution of Fc effector functions to protection in vivo inversely correlates with viral growth inhibition activity in vitro. Overall, our findings advance the understanding of NA antibody response and provide important insights into the development of a broadly protective influenza vaccine.
논문정보
- Research article
- 2023년 11월 (BRIC 등록일 2023-11-16)
- 국내+국외 연구진
- 의약학 > 면역의학
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