Molecular divergence and convergence of mammalian antibody responses to the influenza virus hemagglutinin stem
Abstract
Antibody responses to the influenza virus hemagglutinin (HA) stem, a major target for broadly protective vaccine development, have been extensively characterized in humans. However, they remain largely elusive in other natural influenza hosts, including pigs, which are considered intermediate hosts for the emergence of pandemic strains. By leveraging single-cell variable, diversity, and joining (VDJ) sequencing, this study identified 25 porcine antibodies to the HA stem, including two cross-group bnAbs, 14-8 and 15-1, from vaccinated specific-pathogen-free pigs and unvaccinated domestic pigs. Cryogenic electron microscopy analysis showed that 14-8 targeted the well-characterized central stem epitope, whereas 15-1 bound to a linear epitope spanning the HA1/HA2 junction. Additionally, while some porcine and human bnAbs targeted the central stem epitope via convergent molecular signatures, our results revealed a pig-specific recurring binding motif. Overall, our findings provide important insights into the commonalities and uniqueness of antibody responses between different species, which have significant implications for vaccine development for nonhuman animals.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (22)
Huibin Lv
Qi Wen Teo
Tossapol Pholcharee
Wenkan Liu
Department of Biochemistry, University of Illinois Urbana-Champaign
Sawrab Roy
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri
Lei Shi
School of Health Management Guangzhou Medical University Guangzhou China
Akshita B. Gopal
Department of Biochemistry, University of Illinois Urbana-Champaign
Madison R. Ardagh
Department of Biochemistry, University of Illinois Urbana-Champaign
Chunke Chen
The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong
Yuanxin Sun
The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong
Yang Wei Huan
Department of Biochemistry, University of Illinois Urbana-Champaign
Walter N. Harrington
Department of Host-Microbe Interactions, St. Jude Children’s Research Hospital
Arjun Mehta
Department of Biochemistry, University of Illinois Urbana-Champaign
Mateusz Szlembarski
Department of Biochemistry, University of Illinois Urbana-Champaign
Danbi Choi
Department of Biochemistry, University of Illinois Urbana-Champaign
Qihong Gao
The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong
Fiona S. L. Fung
The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong
Fangxiu Xu
Roy J. Carver Biotechnology Center, University of Illinois Urbana-Champaign
Richard J. Webby
Chris K. P. Mok
The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong
Wenjun Ma
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri
Nicholas C. Wu