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Article: The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication.

Baker, Paul J / Bohrer, Andrea C / Castro, Ehydel / Amaral, Eduardo P / Snow-Smith, Maryonne / Torres-Juárez, Flor / Gould, Sydnee T / Queiroz, Artur T L / Fukutani, Eduardo R / Jordan, Cassandra M / Khillan, Jaspal S / Cho, Kyoungin / Barber, Daniel L / Andrade, Bruno B / Johnson, Reed F / Hilligan, Kerry L / Mayer-Barber, Katrin D

bioRxiv : the preprint server for biology

2024

Abstract: SARS-CoV-2 infection leads to vastly divergent clinical outcomes ranging from asymptomatic infection to fatal disease. Co-morbidities, sex, age, host genetics and vaccine status are known to affect disease severity. Yet, how the inflammatory milieu of ... ...

Abstract	SARS-CoV-2 infection leads to vastly divergent clinical outcomes ranging from asymptomatic infection to fatal disease. Co-morbidities, sex, age, host genetics and vaccine status are known to affect disease severity. Yet, how the inflammatory milieu of the lung at the time of SARS-CoV-2 exposure impacts the control of viral replication remains poorly understood. We demonstrate here that immune events in the mouse lung closely preceding SARS-CoV-2 infection significantly impact viral control and we identify key innate immune pathways required to limit viral replication. A diverse set of pulmonary inflammatory stimuli, including resolved antecedent respiratory infections with
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.27.586885
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication

Baker, Paul J / Bohrer, Andrea C / Castro, Ehydel / Amaral, Eduardo P / Snow-Smith, Maryonne / Torres-Juarez, Flor / Gould, Sydnee T / Queiroz, Artur TL / Fukutani, Eduardo R / Jordan, Cassandra M / Khillan, Jaspal S / Cho, Kyoungin / Barber, Daniel L / Andrade, Bruno B / Johnson, Reed F / Hilligan, Kerry L / Mayer-Barber, Katrin D

bioRxiv

Abstract	SARS-CoV-2 infection leads to vastly divergent clinical outcomes ranging from asymptomatic infection to fatal disease. Co-morbidities, sex, age, host genetics and vaccine status are known to affect disease severity. Yet, how the inflammatory milieu of the lung at the time of SARS-CoV-2 exposure impacts the control of viral replication remains poorly understood. We demonstrate here that immune events in the mouse lung closely preceding SARS-CoV-2 infection significantly impact viral control and we identify key innate immune pathways required to limit viral replication. A diverse set of pulmonary inflammatory stimuli, including resolved antecedent respiratory infections with S. aureus or influenza, ongoing pulmonary M. tuberculosis infection, ovalbumin/alum-induced asthma or airway administration of defined TLR ligands and recombinant cytokines, all establish an antiviral state in the lung that restricts SARS-CoV-2 replication upon infection. In addition to antiviral type I interferons, the broadly inducible inflammatory cytokines TNFα and IL-1 precondition the lung for enhanced viral control. Collectively, our work shows that SARS-CoV-2 may benefit from an immunologically quiescent lung microenvironment and suggests that heterogeneity in pulmonary inflammation that precedes or accompanies SARS-CoV-2 exposure may be a significant factor contributing to the population-wide variability in COVID-19 disease outcomes.
Keywords	covid19
Language	English
Publishing date	2024-03-27
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2024.03.27.586885
Database	COVID19

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Article: SARS-CoV-2 seroassay optimization and performance in a population with high background reactivity in Mali.

Sagara, Issaka / Woodford, John / Dicko, Alassane / Zeguime, Amatigue / Doucoure, M'Bouye / Kwan, Jennifer / Zaidi, Irfan / Doritchamou, Justin / Snow-Smith, Maryonne / Alani, Nada / Renn, Jonathan / Kosik, Ivan / Holly, Jaroslav / Yewdell, Jonathan / Esposito, Dominic / Sadtler, Kaitlyn / Duffy, Patrick

medRxiv : the preprint server for health sciences

2021

Abstract: Serological tests are an indispensable tool to understand the epidemiology of the SARS-CoV-2 pandemic, particularly in areas where molecular diagnostics are limited. Poor assay performance may hinder the utility of these tests, including high rates of ... ...

Abstract	Serological tests are an indispensable tool to understand the epidemiology of the SARS-CoV-2 pandemic, particularly in areas where molecular diagnostics are limited. Poor assay performance may hinder the utility of these tests, including high rates of false-positivity previously reported in sub-Saharan Africa. From 312 Malian samples collected prior to 2020, we measured antibodies to the commonly tested SARS-CoV-2 antigens and four other betacoronaviruses by ELISA, and assessed functional cross-reactivity in a subset by SARS-CoV-2 pseudovirus neutralization assay. We then evaluated the performance of an ELISA developed in the US, using two-antigen SARS-CoV-2 spike protein and receptor-binding domain. To optimize test performance, we compared single and two-antigen approaches using existing assay cutoffs and population-specific cutoffs for Malian control samples (positive and negative). Background reactivity to SARS-CoV-2 antigens was common in pre-pandemic samples compared to US controls (43.4% (135/311) for spike protein, 22.8% (71/312) for RBD, and 33.9% (79/233) for nucleocapsid protein). SARS-CoV-2 reactivity correlated weakly with other betacoronavirus reactivity, varied between Malian communities, and increased with age. No pre-pandemic samples demonstrated functional activity. Regardless of the cutoffs applied, specificity improved using a two-antigen approach. Test performance was optimal using a two-antigen assay with population-specific cutoffs derived from ROC curve analysis [Sensitivity: 73.9% (51.6-89.8), Specificity: 99.4% (97.7-99.9)]. In the setting of high background reactivity, such as sub-Saharan Africa, SARS-CoV-2 serological assays need careful qualification is to characterize the epidemiology of disease, prevent unnecessary harm, and allocate resources for targeted control measures.
Language	English
Publishing date	2021-03-12
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.03.08.21252784
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Severe Acute Respiratory Syndrome Coronavirus 2 Seroassay Performance and Optimization in a Population With High Background Reactivity in Mali.

Woodford, John / Sagara, Issaka / Dicko, Alassane / Zeguime, Amatigue / Doucoure, M'Bouye / Kwan, Jennifer / Zaidi, Irfan / Doritchamou, Justin / Snow-Smith, Maryonne / Alani, Nada / Renn, Jonathan / Kosik, Ivan / Holly, Jaroslav / Yewdell, Jonathan / Esposito, Dominic / Sadtler, Kaitlyn / Duffy, Patrick

The Journal of infectious diseases

2021 Volume 224, Issue 12, Page(s) 2001–2009

Abstract: Background: False positivity may hinder the utility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests in sub-Saharan Africa.: Methods: From 312 Malian samples collected before 2020, we measured antibodies to the ... ...

Abstract	Background: False positivity may hinder the utility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests in sub-Saharan Africa. Methods: From 312 Malian samples collected before 2020, we measured antibodies to the commonly tested SARS-CoV-2 antigens and 4 other betacoronaviruses by enzyme-linked immunosorbent assay (ELISA). In a subset of samples, we assessed antibodies to a panel of Plasmodium falciparum antigens by suspension bead array and functional antiviral activity by SARS-CoV-2 pseudovirus neutralization assay. We then evaluated the performance of an ELISA using SARS-CoV-2 spike protein and receptor-binding domain developed in the United States using Malian positive and negative control samples. To optimize test performance, we compared single- and 2-antigen approaches using existing assay cutoffs and population-specific cutoffs. Results: Background reactivity to SARS-CoV-2 antigens was common in prepandemic Malian samples. The SARS-CoV-2 reactivity varied between communities, increased with age, and correlated negligibly/weakly with other betacoronavirus and P falciparum antibodies. No prepandemic samples demonstrated functional activity. Regardless of the cutoffs applied, test specificity improved using a 2-antigen approach. Test performance was optimal using a 2-antigen assay with population-specific cutoffs (sensitivity, 73.9% [95% confidence interval {CI}, 51.6-89.8]; specificity, 99.4% [95% CI, 97.7-99.9]). Conclusions: We have addressed the problem of SARS-CoV-2 seroassay performance in Africa by using a 2-antigen assay with cutoffs defined by performance in the target population.
MeSH term(s)	Adult ; Antibodies, Viral/blood ; COVID-19/blood ; COVID-19/epidemiology ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoglobulin G ; Mali/epidemiology ; SARS-CoV-2/immunology ; Sensitivity and Specificity ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/immunology
Chemical Substances	Antibodies, Viral ; Immunoglobulin G ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2021-10-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiab498
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Aotus nancymaae model predicts human immune response to the placental malaria vaccine candidate VAR2CSA.

Doritchamou, Justin / Nielsen, Morten A / Chêne, Arnaud / Viebig, Nicola K / Lambert, Lynn E / Sander, Adam F / Semblat, Jean-Philippe / Hundt, Sophia / Orr-Gonzalez, Sachy / Janitzek, Christoph Mikkel / Spiegel, Alicia J / Clemmensen, Stine B / Thomas, Marvin L / Nason, Martha C / Snow-Smith, Maryonne / Barnafo, Emma K / Shiloach, Joseph / Chen, Beth B / Nadakal, Steven /

Highsmith, Kendrick / Ouahes, Tarik / Conteh, Solomon / Sharma, Ankur / Torano, Holly / Butler, Brandi / Reiter, Karine / Rausch, Kelly M / Scaria, Puthupparampil V / Anderson, Charles / Narum, David L / Salanti, Ali / Fried, Michal / Theander, Thor G / Gamain, Benoit / Duffy, Patrick E

Lab animal

2023 Volume 52, Issue 12, Page(s) 315–323

Abstract: Placental malaria vaccines (PMVs) are being developed to prevent severe sequelae of placental malaria (PM) in pregnant women and their offspring. The leading candidate vaccine antigen VAR2CSA mediates parasite binding to placental receptor chondroitin ... ...

Abstract	Placental malaria vaccines (PMVs) are being developed to prevent severe sequelae of placental malaria (PM) in pregnant women and their offspring. The leading candidate vaccine antigen VAR2CSA mediates parasite binding to placental receptor chondroitin sulfate A (CSA). Despite promising results in small animal studies, recent human trials of the first two PMV candidates (PAMVAC and PRIMVAC) generated limited cross-reactivity and cross-inhibitory activity to heterologous parasites. Here we immunized Aotus nancymaae monkeys with three PMV candidates (PAMVAC, PRIMVAC and ID1-ID2a_M1010) adjuvanted with Alhydrogel, and exploited the model to investigate boosting of functional vaccine responses during PM episodes as well as with nanoparticle antigens. PMV candidates induced high levels of antigen-specific IgG with significant cross-reactivity across PMV antigens by enzyme-linked immunosorbent assay. Conversely, PMV antibodies recognized native VAR2CSA and blocked CSA adhesion of only homologous parasites and not of heterologous parasites. PM episodes did not significantly boost VAR2CSA antibody levels or serum functional activity; nanoparticle and monomer antigens alike boosted serum reactivity but not functional activities. Overall, PMV candidates induced functional antibodies with limited heterologous activity in Aotus monkeys, similar to responses reported in humans. The Aotus model appears suitable for preclinical downselection of PMV candidates and assessment of antibody boosting by PM episodes.
MeSH term(s)	Animals ; Humans ; Female ; Pregnancy ; Placenta/parasitology ; Malaria Vaccines ; Malaria, Falciparum/prevention & control ; Malaria, Falciparum/parasitology ; Plasmodium falciparum ; Antigens, Protozoan ; Antibodies, Protozoan ; Malaria/prevention & control ; Aotidae ; Immunity
Chemical Substances	Malaria Vaccines ; Antigens, Protozoan ; Antibodies, Protozoan
Language	English
Publishing date	2023-11-06
Publishing country	United States
Document type	Journal Article
ISSN	1548-4475
ISSN (online)	1548-4475
DOI	10.1038/s41684-023-01274-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: SARS-CoV-2 seroassay optimization and performance in a population with high background reactivity in Mali

medRxiv

Abstract	Serological tests are an indispensable tool to understand the epidemiology of the SARS-CoV-2 pandemic, particularly in areas where molecular diagnostics are limited. Poor assay performance may hinder the utility of these tests, including high rates of false-positivity previously reported in sub-Saharan Africa. From 312 Malian samples collected prior to 2020, we measured antibodies to the commonly tested SARS-CoV-2 antigens and four other betacoronaviruses by ELISA, and assessed functional cross-reactivity in a subset by SARS-CoV-2 pseudovirus neutralization assay. We then evaluated the performance of an ELISA developed in the US, using two-antigen SARS-CoV-2 spike protein and receptor-binding domain. To optimize test performance, we compared single and two-antigen approaches using existing assay cutoffs and population-specific cutoffs for Malian control samples (positive and negative). Background reactivity to SARS-CoV-2 antigens was common in pre-pandemic samples compared to US controls (43.4% (135/311) for spike protein, 22.8% (71/312) for RBD, and 33.9% (79/233) for nucleocapsid protein). SARS-CoV-2 reactivity correlated weakly with other betacoronavirus reactivity, varied between Malian communities, and increased with age. No pre-pandemic samples demonstrated functional activity. Regardless of the cutoffs applied, specificity improved using a two-antigen approach. Test performance was optimal using a two-antigen assay with population-specific cutoffs derived from ROC curve analysis [Sensitivity: 73.9% (51.6-89.8), Specificity: 99.4% (97.7-99.9)]. In the setting of high background reactivity, such as sub-Saharan Africa, SARS-CoV-2 serological assays need careful qualification is to characterize the epidemiology of disease, prevent unnecessary harm, and allocate resources for targeted control measures.
Keywords	covid19
Language	English
Publishing date	2021-03-12
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.03.08.21252784
Database	COVID19

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Article ; Online: Antimalarial antibody repertoire defined by plasma IG proteomics and single B cell IG sequencing.

Coelho, Camila H / Nadakal, Steven T / Gonzales Hurtado, Patricia / Morrison, Robert / Galson, Jacob D / Neal, Jillian / Wu, Yimin / King, C Richter / Price, Virginia / Miura, Kazutoyo / Wong-Madden, Sharon / Alamou Doritchamou, Justin Yai / Narum, David L / MacDonald, Nicholas J / Snow-Smith, Maryonne / Vignali, Marissa / Taylor, Justin J / Lefranc, Marie-Paule / Trück, Johannes /

Long, Carole A / Healy, Sara A / Sagara, Issaka / Fried, Michal / Duffy, Patrick E

JCI insight

2020 Volume 5, Issue 22

Abstract: Plasma antimalarial Ab can mediate antiparasite immunity but has not previously been characterized at the molecular level. Here, we develop an innovative strategy to characterize humoral responses by integrating profiles of plasma immunoglobulins (IGs) ... ...

Abstract	Plasma antimalarial Ab can mediate antiparasite immunity but has not previously been characterized at the molecular level. Here, we develop an innovative strategy to characterize humoral responses by integrating profiles of plasma immunoglobulins (IGs) or Abs with those expressed on B cells as part of the B cell receptor. We applied this strategy to define plasma IG and to determine variable (V) gene usage after vaccination with the Plasmodium falciparum zygote antigen Pfs25. Using proteomic tools coupled with bulk immunosequencing data, we determined human antigen-binding fragment [F(ab')2] peptide sequences from plasma IG of adults who received 4 doses of Pfs25-EPA/Alhydrogel. Specifically, Pfs25 antigen-specific F(ab')2 peptides (Pfs25-IG) were aligned to cDNA sequences of IG heavy (IGH) chain complementarity determining region 3 from a data set generated by total peripheral B cell immunosequencing of the entire vaccinated population. IGHV4 was the most commonly identified IGHV subgroup of Pfs25-IG, a pattern that was corroborated by V heavy/V light chain sequencing of Pfs25-specific single B cells from 5 vaccinees and by matching plasma Pfs25-IG peptides and V-(D)-J sequences of Pfs25-specific single B cells from the same donor. Among 13 recombinant human mAbs generated from IG sequences of Pfs25-specific single B cells, a single IGHV4 mAb displayed strong neutralizing activity, reducing the number of P. falciparum oocysts in infected mosquitoes by more than 80% at 100 μg/mL. Our approach characterizes the human plasma Ab repertoire in response to the Pfs25-EPA/Alhydrogel vaccine and will be useful for studying circulating Abs in response to other vaccines as well as those induced during infections or autoimmune disorders.
MeSH term(s)	Adjuvants, Immunologic ; Adolescent ; Adult ; Antibodies, Monoclonal/blood ; Antibodies, Monoclonal/immunology ; Antibodies, Protozoan/blood ; Antibodies, Protozoan/immunology ; Antigens, Protozoan/immunology ; Antimalarials/administration & dosage ; Antimalarials/immunology ; B-Lymphocytes/immunology ; Clinical Trials as Topic ; Female ; Humans ; Immunoglobulins/blood ; Immunoglobulins/immunology ; Malaria Vaccines/administration & dosage ; Malaria Vaccines/immunology ; Malaria, Falciparum/blood ; Malaria, Falciparum/immunology ; Malaria, Falciparum/parasitology ; Malaria, Falciparum/prevention & control ; Male ; Middle Aged ; Plasmodium falciparum/immunology ; Protozoan Proteins/immunology ; Vaccination ; Young Adult
Chemical Substances	Adjuvants, Immunologic ; Antibodies, Monoclonal ; Antibodies, Protozoan ; Antigens, Protozoan ; Antimalarials ; Immunoglobulins ; Malaria Vaccines ; Pfs25 protein, Plasmodium falciparum ; Protozoan Proteins
Language	English
Publishing date	2020-11-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.143471
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication.

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Article ; Online: The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication

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Inter-library loan at ZB MED

Article: SARS-CoV-2 seroassay optimization and performance in a population with high background reactivity in Mali.

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Article ; Online: Severe Acute Respiratory Syndrome Coronavirus 2 Seroassay Performance and Optimization in a Population With High Background Reactivity in Mali.

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Article ; Online: Aotus nancymaae model predicts human immune response to the placental malaria vaccine candidate VAR2CSA.

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Article ; Online: SARS-CoV-2 seroassay optimization and performance in a population with high background reactivity in Mali

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Article ; Online: Antimalarial antibody repertoire defined by plasma IG proteomics and single B cell IG sequencing.

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