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Article: Mapping immunodominant sites on the MERS-CoV spike glycoprotein targeted by infection-elicited antibodies in humans.

Addetia, Amin / Stewart, Cameron / Seo, Albert J / Sprouse, Kaitlin R / Asiri, Ayed Y / Al-Mozaini, Maha / Memish, Ziad A / Alshukairi, Abeer / Veesler, David

bioRxiv : the preprint server for biology

2024

Abstract: Middle-East respiratory syndrome coronavirus (MERS-CoV) first emerged in 2012 and causes human infections in endemic regions. Most vaccines and therapeutics in development against MERS-CoV focus on the spike (S) glycoprotein to prevent viral entry into ... ...

Abstract	Middle-East respiratory syndrome coronavirus (MERS-CoV) first emerged in 2012 and causes human infections in endemic regions. Most vaccines and therapeutics in development against MERS-CoV focus on the spike (S) glycoprotein to prevent viral entry into target cells. These efforts, however, are limited by a poor understanding of antibody responses elicited by infection along with their durability, fine specificity and contribution of distinct S antigenic sites to neutralization. To address this knowledge gap, we analyzed S-directed binding and neutralizing antibody titers in plasma collected from individuals infected with MERS-CoV in 2017-2019 (prior to the COVID-19 pandemic). We observed that binding and neutralizing antibodies peak 1 to 6 weeks after symptom onset/hospitalization, persist for at least 6 months, and broadly neutralize human and camel MERS-CoV strains. We show that the MERS-CoV S
Language	English
Publishing date	2024-04-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.31.586409
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Article ; Online: Persistent immune imprinting occurs after vaccination with the COVID-19 XBB.1.5 mRNA booster in humans.

Tortorici, M Alejandra / Addetia, Amin / Seo, Albert J / Brown, Jack / Sprouse, Kaiti / Logue, Jenni / Clark, Erica / Franko, Nicholas / Chu, Helen / Veesler, David

Immunity

2024 Volume 57, Issue 4, Page(s) 904–911.e4

Abstract: Immune imprinting describes how the first exposure to a virus shapes immunological outcomes of subsequent exposures to antigenically related strains. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron breakthrough infections and ... ...

Abstract	Immune imprinting describes how the first exposure to a virus shapes immunological outcomes of subsequent exposures to antigenically related strains. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron breakthrough infections and bivalent COVID-19 vaccination primarily recall cross-reactive memory B cells induced by prior Wuhan-Hu-1 spike mRNA vaccination rather than priming Omicron-specific naive B cells. These findings indicate that immune imprinting occurs after repeated Wuhan-Hu-1 spike exposures, but whether it can be overcome remains unclear. To understand the persistence of immune imprinting, we investigated memory and plasma antibody responses after administration of the updated XBB.1.5 COVID-19 mRNA vaccine booster. We showed that the XBB.1.5 booster elicited neutralizing antibody responses against current variants that were dominated by recall of pre-existing memory B cells previously induced by the Wuhan-Hu-1 spike. Therefore, immune imprinting persists after multiple exposures to Omicron spikes through vaccination and infection, including post XBB.1.5 booster vaccination, which will need to be considered to guide future vaccination.
MeSH term(s)	Humans ; COVID-19 Vaccines ; COVID-19/prevention & control ; SARS-CoV-2 ; Antibodies, Neutralizing ; RNA, Messenger/genetics ; Vaccination ; Antibodies, Viral
Chemical Substances	COVID-19 Vaccines ; Antibodies, Neutralizing ; RNA, Messenger ; Antibodies, Viral
Language	English
Publishing date	2024-03-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2024.02.016
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Article ; Online: Transfer of skin microbiota between two dissimilar autologous microenvironments: A pilot study.

Perin, Benji / Addetia, Amin / Qin, Xuan

PloS one

2019 Volume 14, Issue 12, Page(s) e0226857

Abstract: Dysbiosis of skin microbiota is associated with several inflammatory skin conditions, including atopic dermatitis, acne, and hidradenitis suppurativa. There is a surge of interest by clinicians and the lay public to explore targeted bacteriotherapy to ... ...

Abstract	Dysbiosis of skin microbiota is associated with several inflammatory skin conditions, including atopic dermatitis, acne, and hidradenitis suppurativa. There is a surge of interest by clinicians and the lay public to explore targeted bacteriotherapy to treat these dermatologic conditions. To date, skin microbiota transplantation studies have focused on moving single, enriched strains of bacteria to target sites rather than a whole community. In this prospective pilot study, we examined the feasibility of transferring unenriched skin microbiota communities between two anatomical sites of the same host. We enrolled four healthy volunteers (median age: 28 [range: 24, 36] years; 2 [50%] female) who underwent collection and transfer of skin microbiota from the forearm to the back unidirectionally. Using culture methods and 16S rRNA V1-V3 deep sequencing, we compared baseline and mixed ("transplant") communities, at T = 0 and T = 24 hours. Our ability to detect movement from one site to the other relied on the inherent diversity of the microenvironment of the antecubital fossa relative to the less diverse back. Comparing bacterial species present in the arm and mixed ("transplant") communities that were absent from the baseline back, we saw evidence of transfer of a partial DNA signature; our methods limit conclusions regarding the viability of transferred organisms. We conclude that unenriched transfer of whole cutaneous microbiota is challenging, but our simple technique, intended to move viable skin organisms from one site to another, is worthy of further investigation.
MeSH term(s)	Adult ; Back/microbiology ; Bacteria/isolation & purification ; Dysbiosis ; Female ; Forearm/microbiology ; Humans ; Male ; Microbiota ; Pilot Projects ; RNA, Ribosomal, 16S ; Skin/microbiology ; Transplantation, Autologous ; Young Adult
Chemical Substances	RNA, Ribosomal, 16S
Language	English
Publishing date	2019-12-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0226857
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Article ; Online: Inactivation of genes in oxidative respiration and iron acquisition pathways in pediatric clinical isolates of Small colony variant Enterobacteriaceae.

Greninger, Alexander L / Addetia, Amin / Tao, Yue / Adler, Amanda / Qin, Xuan

Scientific reports

2021 Volume 11, Issue 1, Page(s) 7457

Abstract: Isolation of bacterial small colony variants (SCVs) from clinical specimens is not uncommon and can fundamentally change the outcome of the associated infections. Bacterial SCVs often emerge with their normal colony phenotype (NCV) co-isolates in the ... ...

Abstract	Isolation of bacterial small colony variants (SCVs) from clinical specimens is not uncommon and can fundamentally change the outcome of the associated infections. Bacterial SCVs often emerge with their normal colony phenotype (NCV) co-isolates in the same sample. The basis of SCV emergence in vivo is not well understood in Gram-negative bacteria. In this study, we interrogated the causal genetic lesions of SCV growth in three pairs of NCV and SCV co-isolates of Escherichia coli, Citrobacter freundii, and Enterobacter hormaechei. We confirmed SCV emergence was attributed to limited genomic mutations: 4 single nucleotide variants in the E. coli SCV, 5 in C. freundii, and 8 in E. hormaechei. In addition, a 10.2 kb chromosomal segment containing 11 genes was deleted in the E. hormaechei SCV isolate. Each SCV had at least one coding change in a gene associated with bacterial oxidative respiration and another involved in iron capture. Chemical and genetic rescue confirmed defects in heme biosynthesis for E. coli and C. freundii and lipoic acid biosynthesis in E. hormaachei were responsible for the SCV phenotype. Prototrophic growth in all 3 SCV Enterobacteriaceae species was unaffected under anaerobic culture conditions in vitro, illustrating how SCVs may persist in vivo.
MeSH term(s)	Aerobiosis/genetics ; Anaerobiosis/genetics ; Biosynthetic Pathways/genetics ; Child ; Colony Count, Microbial ; Drug Resistance, Bacterial/genetics ; Enterobacteriaceae/genetics ; Enterobacteriaceae/growth & development ; Enterobacteriaceae/isolation & purification ; Female ; Gene Silencing ; Genes, Bacterial ; Genetic Variation ; Heme/biosynthesis ; Humans ; Infant ; Iron/metabolism ; Kinetics ; Male ; Microbial Sensitivity Tests ; Phenotype ; Thioctic Acid/biosynthesis ; Whole Genome Sequencing
Chemical Substances	Heme (42VZT0U6YR) ; Thioctic Acid (73Y7P0K73Y) ; Iron (E1UOL152H7)
Language	English
Publishing date	2021-04-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-86764-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat.

Hannon, William W / Roychoudhury, Pavitra / Xie, Hong / Shrestha, Lasata / Addetia, Amin / Jerome, Keith R / Greninger, Alexander L / Bloom, Jesse D

bioRxiv : the preprint server for biology

2022

Abstract: The long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here we use deep sequencing to investigate the transmission of viral genetic variation among individuals ... ...

Abstract	The long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here we use deep sequencing to investigate the transmission of viral genetic variation among individuals during a SARS-CoV-2 outbreak that infected the vast majority of crew members on a fishing boat. We deep-sequenced nasal swabs to characterize the within-host viral population of infected crew members, using experimental duplicates and strict computational filters to ensure accurate variant calling. We find that within-host viral diversity is low in infected crew members. The mutations that did fix in some crew members during the outbreak are not observed at detectable frequencies in any of the sampled crew members in which they are not fixed, suggesting viral evolution involves occasional fixation of low-frequency mutations during transmission rather than persistent maintenance of within-host viral diversity. Overall, our results show that strong transmission bottlenecks dominate viral evolution even during a superspreading event with a very high attack rate.
Language	English
Publishing date	2022-02-09
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.02.09.479546
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Article: Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat.

Hannon, William W / Roychoudhury, Pavitra / Xie, Hong / Shrestha, Lasata / Addetia, Amin / Jerome, Keith R / Greninger, Alexander L / Bloom, Jesse D

Virus evolution

2022 Volume 8, Issue 2, Page(s) veac052

Abstract: The long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here, we use deep sequencing to investigate the transmission of viral genetic variation among individuals ... ...

Abstract	The long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here, we use deep sequencing to investigate the transmission of viral genetic variation among individuals during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak that infected the vast majority of crew members on a fishing boat. We deep-sequenced nasal swabs to characterize the within-host viral population of infected crew members, using experimental duplicates and strict computational filters to ensure accurate variant calling. We find that within-host viral diversity is low in infected crew members. The mutations that did fix in some crew members during the outbreak are not observed at detectable frequencies in any of the sampled crew members in which they are not fixed, suggesting that viral evolution involves occasional fixation of low-frequency mutations during transmission rather than persistent maintenance of within-host viral diversity. Overall, our results show that strong transmission bottlenecks dominate viral evolution even during a superspreading event with a very high attack rate.
Language	English
Publishing date	2022-06-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2818949-8
ISSN	2057-1577
ISSN	2057-1577
DOI	10.1093/ve/veac052
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Article ; Online: Transfer of skin microbiota between two dissimilar autologous microenvironments

Benji Perin / Amin Addetia / Xuan Qin

PLoS ONE, Vol 14, Iss 12, p e

A pilot study.

2019 Volume 0226857

Abstract	Dysbiosis of skin microbiota is associated with several inflammatory skin conditions, including atopic dermatitis, acne, and hidradenitis suppurativa. There is a surge of interest by clinicians and the lay public to explore targeted bacteriotherapy to treat these dermatologic conditions. To date, skin microbiota transplantation studies have focused on moving single, enriched strains of bacteria to target sites rather than a whole community. In this prospective pilot study, we examined the feasibility of transferring unenriched skin microbiota communities between two anatomical sites of the same host. We enrolled four healthy volunteers (median age: 28 [range: 24, 36] years; 2 [50%] female) who underwent collection and transfer of skin microbiota from the forearm to the back unidirectionally. Using culture methods and 16S rRNA V1-V3 deep sequencing, we compared baseline and mixed ("transplant") communities, at T = 0 and T = 24 hours. Our ability to detect movement from one site to the other relied on the inherent diversity of the microenvironment of the antecubital fossa relative to the less diverse back. Comparing bacterial species present in the arm and mixed ("transplant") communities that were absent from the baseline back, we saw evidence of transfer of a partial DNA signature; our methods limit conclusions regarding the viability of transferred organisms. We conclude that unenriched transfer of whole cutaneous microbiota is challenging, but our simple technique, intended to move viable skin organisms from one site to another, is worthy of further investigation.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Regulatory T Cell-like Response to SARS-CoV-2 in Jamaican Fruit Bats (

Burke, Bradly / Rocha, Savannah M / Zhan, Shijun / Eckley, Miles / Reasoner, Clara / Addetia, Amin / Lewis, Juliette / Fagre, Anna / Charley, Phillida / Richt, Juergen A / Weiss, Susan R / Tjalkens, Ronald B / Veesler, David / Aboellail, Tawfik / Schountz, Tony

bioRxiv : the preprint server for biology

2023

Abstract: Insectivorous Old World horseshoe bats ( : Author summary: Bats are reservoir hosts of many viruses that infect humans, yet little is known about how they host these viruses, principally because of a lack of relevant and susceptible bat experimental ... ...

Abstract	Insectivorous Old World horseshoe bats ( Author summary: Bats are reservoir hosts of many viruses that infect humans, yet little is known about how they host these viruses, principally because of a lack of relevant and susceptible bat experimental infection models. Although SARS-CoV-2 originated in bats, no robust infection models of bats have been established. We determined that Jamaican fruit bats are poorly susceptible to SARS-CoV-2; however, their lungs can be transduced with human ACE2, which renders them susceptible to SARS-CoV-2. Despite robust infection of the lungs and diminishment of pulmonary cellularity, the bats showed no overt signs of disease and cleared the infection after two weeks. Despite clearance of infection, only low-titer antibody responses occurred and only a single bat made neutralizing antibody. Assessment of the CD4
Language	English
Publishing date	2023-02-20
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.13.528205
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Article ; Online: Sensitive Recovery of Complete SARS-CoV-2 Genomes from Clinical Samples by Use of Swift Biosciences' SARS-CoV-2 Multiplex Amplicon Sequencing Panel.

Addetia, Amin / Lin, Michelle J / Peddu, Vikas / Roychoudhury, Pavitra / Jerome, Keith R / Greninger, Alexander L

Journal of clinical microbiology

2020 Volume 59, Issue 1

MeSH term(s)	COVID-19/diagnosis ; COVID-19 Nucleic Acid Testing/methods ; Gene Library ; Genome, Viral/genetics ; Humans ; Phylogeny ; RNA, Viral/genetics ; SARS-CoV-2/genetics ; Whole Genome Sequencing/methods
Chemical Substances	RNA, Viral
Keywords	covid19
Language	English
Publishing date	2020-12-17
Publishing country	United States
Document type	Evaluation Study ; Letter
ZDB-ID	390499-4
ISSN	1098-660X ; 0095-1137
ISSN (online)	1098-660X
ISSN	0095-1137
DOI	10.1128/JCM.02226-20
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Zs.A 1188: Show issues

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Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Structural changes in the SARS-CoV-2 spike E406W mutant escaping a clinical monoclonal antibody cocktail.

Addetia, Amin / Park, Young-Jun / Starr, Tyler / Greaney, Allison J / Sprouse, Kaitlin R / Bowen, John E / Tiles, Sasha W / Van Voorhis, Wesley C / Bloom, Jesse D / Corti, Davide / Walls, Alexandra C / Veesler, David

Cell reports

2023 Volume 42, Issue 6, Page(s) 112621

Abstract: Continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is eroding antibody responses elicited by prior vaccination and infection. The SARS-CoV-2 receptor-binding domain (RBD) E406W mutation abrogates neutralization mediated ... ...

Abstract	Continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is eroding antibody responses elicited by prior vaccination and infection. The SARS-CoV-2 receptor-binding domain (RBD) E406W mutation abrogates neutralization mediated by the REGEN-COV therapeutic monoclonal antibody (mAb) COVID-19 cocktail and the AZD1061 (COV2-2130) mAb. Here, we show that this mutation remodels the receptor-binding site allosterically, thereby altering the epitopes recognized by these three mAbs and vaccine-elicited neutralizing antibodies while remaining functional. Our results demonstrate the spectacular structural and functional plasticity of the SARS-CoV-2 RBD, which is continuously evolving in emerging SARS-CoV-2 variants, including currently circulating strains that are accumulating mutations in the antigenic sites remodeled by the E406W substitution.
MeSH term(s)	Humans ; SARS-CoV-2 ; Combined Antibody Therapeutics ; COVID-19 ; Antibodies, Viral ; Antibodies, Neutralizing ; Antibodies, Monoclonal ; Spike Glycoprotein, Coronavirus ; Neutralization Tests
Chemical Substances	Combined Antibody Therapeutics ; Antibodies, Viral ; Antibodies, Neutralizing ; Antibodies, Monoclonal ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2023-05-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112621
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