Humoral Immunity Profiling to Pandemic and Bat‐Derived Coronavirus Variants: A Geographical Comparison

Abstract Dynamic pathogen exposure may impact the immunological response to SARS‐CoV‐2 (SCV2). One potential explanation for the lack of severe SCV2‐related morbidity and mortality in Southeast Asia is prior exposure to related betacoronaviruses. Recent discoveries of SCV2‐related betacoronaviruses...

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Main Authors: Parinaz Fathi, Andrea Lucia Alfonso, Christina Yek, Zoe Putman, Matthew Drew, Dominic Esposito, Irfan Zaidi, Sophana Chea, Sokna Ly, Rathanak Sath, Chanthap Lon, Huch Chea, Rithea Leang, Rekol Huy, Sovann Ly, Heng Seng, Chee Wah Tan, Feng Zhu, Lin‐Fa Wang, Fabiano Oliveira, Kaitlyn Sadtler, Jessica Manning
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202403503
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author Parinaz Fathi
Andrea Lucia Alfonso
Christina Yek
Zoe Putman
Matthew Drew
Dominic Esposito
Irfan Zaidi
Sophana Chea
Sokna Ly
Rathanak Sath
Chanthap Lon
Huch Chea
Rithea Leang
Rekol Huy
Sovann Ly
Heng Seng
Chee Wah Tan
Feng Zhu
Lin‐Fa Wang
Fabiano Oliveira
Kaitlyn Sadtler
Jessica Manning
author_facet Parinaz Fathi
Andrea Lucia Alfonso
Christina Yek
Zoe Putman
Matthew Drew
Dominic Esposito
Irfan Zaidi
Sophana Chea
Sokna Ly
Rathanak Sath
Chanthap Lon
Huch Chea
Rithea Leang
Rekol Huy
Sovann Ly
Heng Seng
Chee Wah Tan
Feng Zhu
Lin‐Fa Wang
Fabiano Oliveira
Kaitlyn Sadtler
Jessica Manning
author_sort Parinaz Fathi
collection DOAJ
description Abstract Dynamic pathogen exposure may impact the immunological response to SARS‐CoV‐2 (SCV2). One potential explanation for the lack of severe SCV2‐related morbidity and mortality in Southeast Asia is prior exposure to related betacoronaviruses. Recent discoveries of SCV2‐related betacoronaviruses from horseshoe bats (Rhinolophus sinicus) in Thailand, Laos, and Cambodia suggest the potential for bat‐to‐human spillover exposures in the region. In this work, serum antibodies to protein constructs from SCV2 and a representative bat coronavirus isolated in Cambodia (RshSTT182) are measured in pre‐pandemic Cambodian human sera using ELISA assays. Of 293 Cambodian samples tested (N = 131 with acute malaria, n = 162 with acute undifferentiated febrile illness), 32 (10.9%) are seropositive for SCV2 based on established Spike and receptor‐binding domain (RBD) cutoffs. Within SCV2 seropositive samples, 16 (50%) have higher antibody levels to antigens from the representative virus RshSTT182 versus SCV2 antigens; competitive binding ELISA assays demonstrate inhibition of reactivity to SCV2 Spike after pre‐incubation with RshSTT182 Spike. Surrogate virus neutralization tests demonstrate that 8/30 (26.7%) SCV2 ELISA positive pre‐pandemic Cambodian samples have neutralizing activity against SCV2, while 14/30 (46.7%) have activity against other SCV2‐related betacoronaviruses. These data suggest that exposure to related betacoronaviruses may elicit cross‐reactive immunity to SCV2 prior to the global pandemic.
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spelling doaj-art-12633665e4694115b99977749b98e41f2025-01-09T11:44:45ZengWileyAdvanced Science2198-38442025-01-01121n/an/a10.1002/advs.202403503Humoral Immunity Profiling to Pandemic and Bat‐Derived Coronavirus Variants: A Geographical ComparisonParinaz Fathi0Andrea Lucia Alfonso1Christina Yek2Zoe Putman3Matthew Drew4Dominic Esposito5Irfan Zaidi6Sophana Chea7Sokna Ly8Rathanak Sath9Chanthap Lon10Huch Chea11Rithea Leang12Rekol Huy13Sovann Ly14Heng Seng15Chee Wah Tan16Feng Zhu17Lin‐Fa Wang18Fabiano Oliveira19Kaitlyn Sadtler20Jessica Manning21Section on Immunoengineering Biomedical Engineering and Technology Acceleration Center National Institute of Biomedical Imaging and Bioengineering Bethesda MD 20892 USASection on Immunoengineering Biomedical Engineering and Technology Acceleration Center National Institute of Biomedical Imaging and Bioengineering Bethesda MD 20892 USALaboratory of Malaria and Vector Research National Institute of Allergy and Infectious Diseases Rockville MD 20892 USAProtein Expression Laboratory NCI RAS Initiative Frederick National Laboratory for Cancer Research Frederick MD 21701 USAProtein Expression Laboratory NCI RAS Initiative Frederick National Laboratory for Cancer Research Frederick MD 21701 USAProtein Expression Laboratory NCI RAS Initiative Frederick National Laboratory for Cancer Research Frederick MD 21701 USALaboratory of Malaria Immunology and Vaccinology National Institute of Allergy and Infectious Diseases Bethesda MD 20892 USAInternational Center of Excellence in Research Cambodia National Institute of Allergy and Infectious Diseases Phnom Penh 120801 CambodiaInternational Center of Excellence in Research Cambodia National Institute of Allergy and Infectious Diseases Phnom Penh 120801 CambodiaInternational Center of Excellence in Research Cambodia National Institute of Allergy and Infectious Diseases Phnom Penh 120801 CambodiaInternational Center of Excellence in Research Cambodia National Institute of Allergy and Infectious Diseases Phnom Penh 120801 CambodiaNational Center for Parasitology, Entomology, and Malaria Control Ministry of Health Phnom Penh 120801 CambodiaNational Center for Parasitology, Entomology, and Malaria Control Ministry of Health Phnom Penh 120801 CambodiaNational Center for Parasitology, Entomology, and Malaria Control Ministry of Health Phnom Penh 120801 CambodiaCambodian Center for Disease Control Ministry of Health Phnom Penh 120407 CambodiaCambodian Center for Disease Control Ministry of Health Phnom Penh 120407 CambodiaProgramme for Emerging Infectious Diseases Duke‐National University of Singapore Medical School 169857 Singapore SingaporeProgramme for Emerging Infectious Diseases Duke‐National University of Singapore Medical School 169857 Singapore SingaporeProgramme for Emerging Infectious Diseases Duke‐National University of Singapore Medical School 169857 Singapore SingaporeLaboratory of Malaria and Vector Research National Institute of Allergy and Infectious Diseases Rockville MD 20892 USASection on Immunoengineering Biomedical Engineering and Technology Acceleration Center National Institute of Biomedical Imaging and Bioengineering Bethesda MD 20892 USALaboratory of Malaria and Vector Research National Institute of Allergy and Infectious Diseases Rockville MD 20892 USAAbstract Dynamic pathogen exposure may impact the immunological response to SARS‐CoV‐2 (SCV2). One potential explanation for the lack of severe SCV2‐related morbidity and mortality in Southeast Asia is prior exposure to related betacoronaviruses. Recent discoveries of SCV2‐related betacoronaviruses from horseshoe bats (Rhinolophus sinicus) in Thailand, Laos, and Cambodia suggest the potential for bat‐to‐human spillover exposures in the region. In this work, serum antibodies to protein constructs from SCV2 and a representative bat coronavirus isolated in Cambodia (RshSTT182) are measured in pre‐pandemic Cambodian human sera using ELISA assays. Of 293 Cambodian samples tested (N = 131 with acute malaria, n = 162 with acute undifferentiated febrile illness), 32 (10.9%) are seropositive for SCV2 based on established Spike and receptor‐binding domain (RBD) cutoffs. Within SCV2 seropositive samples, 16 (50%) have higher antibody levels to antigens from the representative virus RshSTT182 versus SCV2 antigens; competitive binding ELISA assays demonstrate inhibition of reactivity to SCV2 Spike after pre‐incubation with RshSTT182 Spike. Surrogate virus neutralization tests demonstrate that 8/30 (26.7%) SCV2 ELISA positive pre‐pandemic Cambodian samples have neutralizing activity against SCV2, while 14/30 (46.7%) have activity against other SCV2‐related betacoronaviruses. These data suggest that exposure to related betacoronaviruses may elicit cross‐reactive immunity to SCV2 prior to the global pandemic.https://doi.org/10.1002/advs.202403503antibodiesbatsbetacoronavirusescross‐reactivitySARS‐CoV‐2
spellingShingle Parinaz Fathi
Andrea Lucia Alfonso
Christina Yek
Zoe Putman
Matthew Drew
Dominic Esposito
Irfan Zaidi
Sophana Chea
Sokna Ly
Rathanak Sath
Chanthap Lon
Huch Chea
Rithea Leang
Rekol Huy
Sovann Ly
Heng Seng
Chee Wah Tan
Feng Zhu
Lin‐Fa Wang
Fabiano Oliveira
Kaitlyn Sadtler
Jessica Manning
Humoral Immunity Profiling to Pandemic and Bat‐Derived Coronavirus Variants: A Geographical Comparison
Advanced Science
antibodies
bats
betacoronaviruses
cross‐reactivity
SARS‐CoV‐2
title Humoral Immunity Profiling to Pandemic and Bat‐Derived Coronavirus Variants: A Geographical Comparison
title_full Humoral Immunity Profiling to Pandemic and Bat‐Derived Coronavirus Variants: A Geographical Comparison
title_fullStr Humoral Immunity Profiling to Pandemic and Bat‐Derived Coronavirus Variants: A Geographical Comparison
title_full_unstemmed Humoral Immunity Profiling to Pandemic and Bat‐Derived Coronavirus Variants: A Geographical Comparison
title_short Humoral Immunity Profiling to Pandemic and Bat‐Derived Coronavirus Variants: A Geographical Comparison
title_sort humoral immunity profiling to pandemic and bat derived coronavirus variants a geographical comparison
topic antibodies
bats
betacoronaviruses
cross‐reactivity
SARS‐CoV‐2
url https://doi.org/10.1002/advs.202403503
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