Pre-pandemic SARS-CoV-2-specific IFN-γ and antibody responses were low in Ugandan samples and significantly reduced in HIV-positive specimens

IntroductionWe investigated whether prior SARS-CoV-2-specific IFN-γ and antibody responses in Ugandan COVID-19 pre-pandemic specimens aligned to this population's low disease severity.MethodsWe used nucleoprotein (N), spike (S), NTD, RBD, envelope, membrane, SD1/2-directed IFN-γ ELISpots, and a...

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Main Authors: Hellen Nantambi, Jackson Sembera, Violet Ankunda, Ivan Ssali, Arthur Watelo Kalyebi, Gerald Kevin Oluka, Laban Kato, Bahemuka Ubaldo, Freddie Kibengo, Joseph Ssebwana Katende, Ben Gombe, Claire Baine, Geoffrey Odoch, Susan Mugaba, Obondo James Sande, The COVID-19 Immunoprofiling Team, Pontiano Kaleebu, Jennifer Serwanga
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-04-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1148877/full
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author Hellen Nantambi
Hellen Nantambi
Hellen Nantambi
Jackson Sembera
Jackson Sembera
Violet Ankunda
Ivan Ssali
Arthur Watelo Kalyebi
Arthur Watelo Kalyebi
Gerald Kevin Oluka
Gerald Kevin Oluka
Laban Kato
Bahemuka Ubaldo
Freddie Kibengo
Joseph Ssebwana Katende
Joseph Ssebwana Katende
Ben Gombe
Claire Baine
Geoffrey Odoch
Susan Mugaba
Obondo James Sande
The COVID-19 Immunoprofiling Team
The COVID-19 Immunoprofiling Team
Pontiano Kaleebu
Pontiano Kaleebu
Jennifer Serwanga
Jennifer Serwanga
author_facet Hellen Nantambi
Hellen Nantambi
Hellen Nantambi
Jackson Sembera
Jackson Sembera
Violet Ankunda
Ivan Ssali
Arthur Watelo Kalyebi
Arthur Watelo Kalyebi
Gerald Kevin Oluka
Gerald Kevin Oluka
Laban Kato
Bahemuka Ubaldo
Freddie Kibengo
Joseph Ssebwana Katende
Joseph Ssebwana Katende
Ben Gombe
Claire Baine
Geoffrey Odoch
Susan Mugaba
Obondo James Sande
The COVID-19 Immunoprofiling Team
The COVID-19 Immunoprofiling Team
Pontiano Kaleebu
Pontiano Kaleebu
Jennifer Serwanga
Jennifer Serwanga
author_sort Hellen Nantambi
collection DOAJ
description IntroductionWe investigated whether prior SARS-CoV-2-specific IFN-γ and antibody responses in Ugandan COVID-19 pre-pandemic specimens aligned to this population's low disease severity.MethodsWe used nucleoprotein (N), spike (S), NTD, RBD, envelope, membrane, SD1/2-directed IFN-γ ELISpots, and an S- and N-IgG antibody ELISA to screen for SARS-CoV-2-specific cross-reactivity.ResultsHCoV-OC43-, HCoV-229E-, and SARS-CoV-2-specific IFN-γ occurred in 23, 15, and 17 of 104 specimens, respectively. Cross-reactive IgG was more common against the nucleoprotein (7/110, 15.5%; p = 0.0016, Fishers' Exact) than the spike (3/110, 2.72%). Specimens lacking anti-HuCoV antibodies had higher rates of pre-epidemic SARS-CoV-2-specific IFN-γ cross-reactivity (p-value = 0.00001, Fishers’ exact test), suggesting that exposure to additional factors not examined here might play a role. SARS-CoV-2-specific cross-reactive antibodies were significantly less common in HIV-positive specimens (p=0.017; Fishers' Exact test). Correlations between SARS-CoV-2- and HuCoV-specific IFN-γ responses were consistently weak in both HIV negative and positive specimens.DiscussionThese findings support the existence of pre-epidemic SARS-CoV-2-specific cellular and humoral cross-reactivity in this population. The data do not establish that these virus-specific IFN-γ and antibody responses are entirely specific to SARS-CoV-2. Inability of the antibodies to neutralise SARS-CoV-2 implies that prior exposure did not result in immunity. Correlations between SARS-CoV-2 and HuCoV-specific responses were consistently weak, suggesting that additional variables likely contributed to the pre-epidemic cross-reactivity patterns. The data suggests that surveillance efforts based on the nucleoprotein might overestimate the exposure to SARS-CoV-2 compared to inclusion of additional targets, like the spike protein. This study, while limited in scope, suggests that HIV-positive people are less likely than HIV-negative people to produce protective antibodies against SARS-CoV-2.
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spelling doaj.art-546f6a4b64e04285a89374a02f81b4d12023-04-19T05:10:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-04-011410.3389/fimmu.2023.11488771148877Pre-pandemic SARS-CoV-2-specific IFN-γ and antibody responses were low in Ugandan samples and significantly reduced in HIV-positive specimensHellen Nantambi0Hellen Nantambi1Hellen Nantambi2Jackson Sembera3Jackson Sembera4Violet Ankunda5Ivan Ssali6Arthur Watelo Kalyebi7Arthur Watelo Kalyebi8Gerald Kevin Oluka9Gerald Kevin Oluka10Laban Kato11Bahemuka Ubaldo12Freddie Kibengo13Joseph Ssebwana Katende14Joseph Ssebwana Katende15Ben Gombe16Claire Baine17Geoffrey Odoch18Susan Mugaba19Obondo James Sande20The COVID-19 Immunoprofiling Team21The COVID-19 Immunoprofiling Team22Pontiano Kaleebu23Pontiano Kaleebu24Jennifer Serwanga25Jennifer Serwanga26Medical Research Council (MRC), Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM), Uganda Research Unit, Entebbe, UgandaDepartment of Immunology, Uganda Virus Research Institute, Entebbe, UgandaDepartment of Immunology and Molecular Biology, College of Health Sciences, Makerere University, Kampala, UgandaMedical Research Council (MRC), Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM), Uganda Research Unit, Entebbe, UgandaDepartment of Immunology, Uganda Virus Research Institute, Entebbe, UgandaDepartment of Immunology, Uganda Virus Research Institute, Entebbe, UgandaMedical Research Council (MRC), Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM), Uganda Research Unit, Entebbe, UgandaDepartment of Immunology, Uganda Virus Research Institute, Entebbe, UgandaDepartment of Immunology and Molecular Biology, College of Health Sciences, Makerere University, Kampala, UgandaMedical Research Council (MRC), Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM), Uganda Research Unit, Entebbe, UgandaDepartment of Immunology, Uganda Virus Research Institute, Entebbe, UgandaMedical Research Council (MRC), Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM), Uganda Research Unit, Entebbe, UgandaMedical Research Council (MRC), Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM), Uganda Research Unit, Entebbe, UgandaMedical Research Council (MRC), Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM), Uganda Research Unit, Entebbe, UgandaMedical Research Council (MRC), Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM), Uganda Research Unit, Entebbe, UgandaDepartment of Immunology, Uganda Virus Research Institute, Entebbe, UgandaMedical Research Council (MRC), Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM), Uganda Research Unit, Entebbe, UgandaDepartment of Immunology, Uganda Virus Research Institute, Entebbe, UgandaMedical Research Council (MRC), Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM), Uganda Research Unit, Entebbe, UgandaMedical Research Council (MRC), Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM), Uganda Research Unit, Entebbe, UgandaDepartment of Immunology and Molecular Biology, College of Health Sciences, Makerere University, Kampala, UgandaMedical Research Council (MRC), Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM), Uganda Research Unit, Entebbe, UgandaDepartment of Immunology, Uganda Virus Research Institute, Entebbe, UgandaMedical Research Council (MRC), Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM), Uganda Research Unit, Entebbe, UgandaDepartment of Immunology, Uganda Virus Research Institute, Entebbe, UgandaMedical Research Council (MRC), Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM), Uganda Research Unit, Entebbe, UgandaDepartment of Immunology, Uganda Virus Research Institute, Entebbe, UgandaIntroductionWe investigated whether prior SARS-CoV-2-specific IFN-γ and antibody responses in Ugandan COVID-19 pre-pandemic specimens aligned to this population's low disease severity.MethodsWe used nucleoprotein (N), spike (S), NTD, RBD, envelope, membrane, SD1/2-directed IFN-γ ELISpots, and an S- and N-IgG antibody ELISA to screen for SARS-CoV-2-specific cross-reactivity.ResultsHCoV-OC43-, HCoV-229E-, and SARS-CoV-2-specific IFN-γ occurred in 23, 15, and 17 of 104 specimens, respectively. Cross-reactive IgG was more common against the nucleoprotein (7/110, 15.5%; p = 0.0016, Fishers' Exact) than the spike (3/110, 2.72%). Specimens lacking anti-HuCoV antibodies had higher rates of pre-epidemic SARS-CoV-2-specific IFN-γ cross-reactivity (p-value = 0.00001, Fishers’ exact test), suggesting that exposure to additional factors not examined here might play a role. SARS-CoV-2-specific cross-reactive antibodies were significantly less common in HIV-positive specimens (p=0.017; Fishers' Exact test). Correlations between SARS-CoV-2- and HuCoV-specific IFN-γ responses were consistently weak in both HIV negative and positive specimens.DiscussionThese findings support the existence of pre-epidemic SARS-CoV-2-specific cellular and humoral cross-reactivity in this population. The data do not establish that these virus-specific IFN-γ and antibody responses are entirely specific to SARS-CoV-2. Inability of the antibodies to neutralise SARS-CoV-2 implies that prior exposure did not result in immunity. Correlations between SARS-CoV-2 and HuCoV-specific responses were consistently weak, suggesting that additional variables likely contributed to the pre-epidemic cross-reactivity patterns. The data suggests that surveillance efforts based on the nucleoprotein might overestimate the exposure to SARS-CoV-2 compared to inclusion of additional targets, like the spike protein. This study, while limited in scope, suggests that HIV-positive people are less likely than HIV-negative people to produce protective antibodies against SARS-CoV-2.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1148877/fullSARS-CoV-2Common-cold coronavirusessero-crossreactivityPre-existing IFN-γSub-Saharan AfricaDisease severity
spellingShingle Hellen Nantambi
Hellen Nantambi
Hellen Nantambi
Jackson Sembera
Jackson Sembera
Violet Ankunda
Ivan Ssali
Arthur Watelo Kalyebi
Arthur Watelo Kalyebi
Gerald Kevin Oluka
Gerald Kevin Oluka
Laban Kato
Bahemuka Ubaldo
Freddie Kibengo
Joseph Ssebwana Katende
Joseph Ssebwana Katende
Ben Gombe
Claire Baine
Geoffrey Odoch
Susan Mugaba
Obondo James Sande
The COVID-19 Immunoprofiling Team
The COVID-19 Immunoprofiling Team
Pontiano Kaleebu
Pontiano Kaleebu
Jennifer Serwanga
Jennifer Serwanga
Pre-pandemic SARS-CoV-2-specific IFN-γ and antibody responses were low in Ugandan samples and significantly reduced in HIV-positive specimens
Frontiers in Immunology
SARS-CoV-2
Common-cold coronaviruses
sero-crossreactivity
Pre-existing IFN-γ
Sub-Saharan Africa
Disease severity
title Pre-pandemic SARS-CoV-2-specific IFN-γ and antibody responses were low in Ugandan samples and significantly reduced in HIV-positive specimens
title_full Pre-pandemic SARS-CoV-2-specific IFN-γ and antibody responses were low in Ugandan samples and significantly reduced in HIV-positive specimens
title_fullStr Pre-pandemic SARS-CoV-2-specific IFN-γ and antibody responses were low in Ugandan samples and significantly reduced in HIV-positive specimens
title_full_unstemmed Pre-pandemic SARS-CoV-2-specific IFN-γ and antibody responses were low in Ugandan samples and significantly reduced in HIV-positive specimens
title_short Pre-pandemic SARS-CoV-2-specific IFN-γ and antibody responses were low in Ugandan samples and significantly reduced in HIV-positive specimens
title_sort pre pandemic sars cov 2 specific ifn γ and antibody responses were low in ugandan samples and significantly reduced in hiv positive specimens
topic SARS-CoV-2
Common-cold coronaviruses
sero-crossreactivity
Pre-existing IFN-γ
Sub-Saharan Africa
Disease severity
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1148877/full
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