Decoding antibody response to MERS-CoV in wild dromedary camels
Abstract
Wild dromedary camels in the Arabian Peninsula and Africa have harbored antibodies against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) for decades, predating zoonotic spillover to humans. However, the potency, specificity, and structural characteristics of these antibodies remain poorly understood. Here, we characterize the antibody responses of naturally infected wild dromedary camels in Tunisia, a MERS-CoV-endemic region. Plasma antibodies from nine camels exhibited variable neutralizing activity, generally increasing with age, and were largely autologous, with minimal cross-reactivity to SARS-CoV-1 or SARS-CoV-2. From a VHH antibody library derived from the peripheral blood mononuclear cells (PBMCs) of a single camel (D17), we identified 34 unique sequences with previously unreported germline origins and unusually long complementarity-determining region 3 (CDR3) sequences. Eight representative VHHs, expressed as human Fc fusions, displayed high-affinity binding to the MERS-CoV receptor-binding domain (RBD) and broad neutralization to RBD mutants (IC 50 : 1.05 to 9.55 ng/mL). Crystal structural analysis revealed distinct neutralization mechanisms: VHH-227 fully blocked DPP4 binding, achieving complete neutralization, while VHH-T71, with partial neutralization (~80%), targeted the RBD core subdomain. This study provides comprehensive characterization of wild dromedary antibody responses, identifying novel nanobodies (Nbs) with broad and potent neutralization to naturally occurring RBD mutants. These findings offer insights into camel immunity and highlight promising candidates for MERS-CoV prophylactic and therapeutic development.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (19)
Faten Idoudi
Pasteur Institute of Tunis, Laboratory of Biomolecules, Venoms and Theranostic Applications (LR20IPT01), NanoBioMedika research Team, University Tunis El Manar
Ruoke Wang
Comprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua University
Long Tian
Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry
Ziqing Yang
Comprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua University
Kenn Ka-Heng Chik
State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Peng Chen
Rahma Benabderrazek
Pasteur Institute of Tunis, Laboratory of Biomolecules, Venoms and Theranostic Applications (LR20IPT01), NanoBioMedika research Team, University Tunis El Manar
Lili Fu
Comprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua University
Ruijie Tan
Comprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua University
Sayda Dhaouadi
Pasteur Institute of Tunis, Laboratory of Biomolecules, Venoms and Theranostic Applications (LR20IPT01), NanoBioMedika research Team, University Tunis El Manar
Zakaria Benlasfar
Pasteur Institute of Tunis, Laboratory of Biomolecules, Venoms and Theranostic Applications (LR20IPT01), NanoBioMedika research Team, University Tunis El Manar
Mahmoud Somia
Pasteur Institute of Tunis, Laboratory of Biomolecules, Venoms and Theranostic Applications (LR20IPT01), NanoBioMedika research Team, University Tunis El Manar
Qi Zhang
Xuanling Shi
Comprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua University
Jasper Fuk-Woo Chan
Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Kwok-Yung Yuen
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Xinquan Wang
The Ministry of Education Key Laboratory of Protein Science
Balkiss Bouhaouala-Zahar
Pasteur Institute of Tunis, Laboratory of Biomolecules, Venoms and Theranostic Applications (LR20IPT01), NanoBioMedika research Team, University Tunis El Manar
Linqi Zhang
Pandemic Research Alliance Unit at the University of Hong Kong