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Article ; Online: Serological testing for SARS-CoV-2 antibodies of employees shows low transmission working in a cancer center.

Jeffrey A Meyerhardt / Hong Yue / Radosław P Nowak / Lauren Brais / Chao Ma / Samantha Johnson / Joanna Harrod / Shourya S Roy Burman / Lynn M Hendrickson / Stephanie Fischinger / Galit Alter / William Hahn / Bruce E Johnson / Eric S Fischer

PLoS ONE, Vol 17, Iss 4, p e

2022 Volume 0266791

Abstract: Background The COVID-19 pandemic led to emergency measures to continue patient care and research at a comprehensive cancer center while protecting both employees and patients. Determining exposure and infection rates with SARS-CoV-2 were important to ... ...

Abstract	Background The COVID-19 pandemic led to emergency measures to continue patient care and research at a comprehensive cancer center while protecting both employees and patients. Determining exposure and infection rates with SARS-CoV-2 were important to adjust workplace policies over time. Methods Dana-Farber Cancer Institute (DFCI) has over 7,000 employees. Participation was voluntary. After consent, participants completed questionnaire of demographics, exposures and risk factors for COVID-19 illness at each time point (baseline, 3, 6, and 12 months) along with blood draws for SARS-CoV-2 antibody testing. Primary measure was determination of titers of SARS-CoV-2 spike protein IgG over time. Results In total, 745 employees enrolled from May 2020 to February 2021 (mean [SD] age, 40[14] years; 572[80%] women). From May to July 2020, 47 of 519 employees (9.2%, 95% confidence interval [CI] 6.7-12.0%) tested positive for SARS-CoV-2 spike protein IgG antibodies. Three months later, 40 of 428 employees had positive antibodies (8.5%, 95% CI 6.0-11.0%) with 17 newly positive. At month 6, 78.5% of participants reported having received at least one dose of vaccine and the positivity rate for those vaccinated was 98% (95% CI, 95-100%). Spike protein IgG titers for those vaccinated were 7.9 times higher than participants not vaccinated (median IgG titer = 0.28 for positive antibody but not vaccinated versus 2.2 for vaccinated) but demonstrate evidence of waning over time. Conclusions SARS-CoV-2 antibody positivity remained less than 10% at a single comprehensive cancer center prior to vaccination and there is evidence of waning IgG titers over time after vaccination.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Serological testing for SARS-CoV-2 antibodies of employees shows low transmission working in a cancer center

Jeffrey A. Meyerhardt / Hong Yue / Radosław P. Nowak / Lauren Brais / Chao Ma / Samantha Johnson / Joanna Harrod / Shourya S. Roy Burman / Lynn M. Hendrickson / Stephanie Fischinger / Galit Alter / William Hahn / Bruce E. Johnson / Eric S. Fischer

PLoS ONE, Vol 17, Iss

2022 Volume 4

Abstract	Background The COVID-19 pandemic led to emergency measures to continue patient care and research at a comprehensive cancer center while protecting both employees and patients. Determining exposure and infection rates with SARS-CoV-2 were important to adjust workplace policies over time. Methods Dana-Farber Cancer Institute (DFCI) has over 7,000 employees. Participation was voluntary. After consent, participants completed questionnaire of demographics, exposures and risk factors for COVID-19 illness at each time point (baseline, 3, 6, and 12 months) along with blood draws for SARS-CoV-2 antibody testing. Primary measure was determination of titers of SARS-CoV-2 spike protein IgG over time. Results In total, 745 employees enrolled from May 2020 to February 2021 (mean [SD] age, 40[14] years; 572[80%] women). From May to July 2020, 47 of 519 employees (9.2%, 95% confidence interval [CI] 6.7–12.0%) tested positive for SARS-CoV-2 spike protein IgG antibodies. Three months later, 40 of 428 employees had positive antibodies (8.5%, 95% CI 6.0–11.0%) with 17 newly positive. At month 6, 78.5% of participants reported having received at least one dose of vaccine and the positivity rate for those vaccinated was 98% (95% CI, 95–100%). Spike protein IgG titers for those vaccinated were 7.9 times higher than participants not vaccinated (median IgG titer = 0.28 for positive antibody but not vaccinated versus 2.2 for vaccinated) but demonstrate evidence of waning over time. Conclusions SARS-CoV-2 antibody positivity remained less than 10% at a single comprehensive cancer center prior to vaccination and there is evidence of waning IgG titers over time after vaccination.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: IFN-γ independent markers of Mycobacterium tuberculosis exposure among male South African gold minersResearch in context

Leela R.L. Davies / Malisa T. Smith / Deniz Cizmeci / Stephanie Fischinger / Jessica Shih-Lu Lee / Lenette L. Lu / Erik D. Layton / Alison D. Grant / Katherine Fielding / Catherine M. Stein / W. Henry Boom / Thomas R. Hawn / Sarah M. Fortune / Robert S. Wallis / Gavin J. Churchyard / Galit Alter / Chetan Seshadri

EBioMedicine, Vol 93, Iss , Pp 104678- (2023)

2023

Abstract: Summary: Background: The prevalence of tuberculosis among men who work in the gold mines of South Africa is among the highest in the world, but a fraction of miners demonstrate consistently negative results upon tuberculin skin test (TST) and IFN-γ ... ...

Abstract	Summary: Background: The prevalence of tuberculosis among men who work in the gold mines of South Africa is among the highest in the world, but a fraction of miners demonstrate consistently negative results upon tuberculin skin test (TST) and IFN-γ release assay (IGRA). We hypothesized that these “resisters” (RSTRs) may display unconventional immune signatures of exposure to M. tuberculosis (M.tb). Methods: In a cohort of RSTRs and matched controls with latent TB infection (LTBI), we profiled the functional breadth of M.tb antigen-specific T cell and antibody responses using multi-parameter flow cytometry and systems serology, respectively. Findings: RSTRs and LTBI controls both exhibited IFN-γ independent T-cell and IgG antibody responses to M.tb-specific antigens ESAT-6 and CFP-10. Antigen-specific antibody Fc galactosylation and sialylation were higher among RSTRs. In a combined T-cell and antibody analysis, M.tb lysate-stimulated TNF secretion by T cells correlated positively with levels of purified protein derivative-specific IgG. A multivariate model of the combined data was able to differentiate RSTR and LTBI subjects. Interpretation: IFN-γ independent immune signatures of exposure to M.tb, which are not detected by approved clinical diagnostics, are readily detectable in an occupational cohort uniquely characterized by intense and long-term infection pressure. Further, TNF may mediate a coordinated response between M.tb-specific T-cells and B-cells. Funding: This work was supported by the US National Institutes of Health (R01-AI124348 to Boom, Stein, and Hawn; R01-AI125189 and R01-AI146072 to Seshadri; and 75N93019C00071 to Fortune, Alter, Seshadri, and Boom), the Doris Duke Charitable Foundation (Davies), the Bill & Melinda Gates Foundation (OPP1151836 and OPP1109001 to Hawn; and OPP1151840 to Alter), Mass Life Science Foundation (Fortune), and Good Ventures Fund (Fortune).
Keywords	Human ; T cell ; B cell ; Antibody ; Mycobacterium tuberculosis ; Resister ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	616
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: IgG3 collaborates with IgG1 and IgA to recruit effector function in RV144 vaccinees

Stephanie Fischinger / Sepideh Dolatshahi / Madeleine F. Jennewein / Supachai Rerks-Ngarm / Punnee Pitisuttithum / Sorachai Nitayaphan / Nelson Michael / Sandhya Vasan / Margaret E. Ackerman / Hendrik Streeck / Galit Alter

JCI Insight, Vol 5, Iss

2020 Volume 21

Abstract: While the RV144 HIV vaccine trial led to moderately reduced risk of HIV acquisition, emerging data from the HVTN702 trial point to the critical need to reexamine RV144-based correlates of reduced risk of protection. While in RV144, the induction of V2- ... ...

Abstract	While the RV144 HIV vaccine trial led to moderately reduced risk of HIV acquisition, emerging data from the HVTN702 trial point to the critical need to reexamine RV144-based correlates of reduced risk of protection. While in RV144, the induction of V2-binding, non-IgA, IgG3 antibody responses with nonneutralizing functions were linked to reduced risk of infection, the interactions between these signatures remain unclear. Thus, here we comprehensively profile the humoral immune response in 300 RV144 vaccinees to decipher the relationships between humoral biomarkers of protection. We found that vaccine-specific IgG1, IgG3, and IgA were highly correlated. However, ratios of IgG1:IgG3:IgA provided insights into subclass/isotype polyclonal functional regulation. For instance, in the absence of high IgG1 levels, IgG3 antibodies exhibited limited functional activity, pointing to IgG3 as a critical contributor, but not sole driver, of effective antiviral humoral immunity. Higher IgA levels were linked to enhanced antibody effector function, including neutrophil phagocytosis (ADNP), complement deposition (ADCD), and antibody-dependent NK degranulation (CD107a), some of which were increased in infected vaccinees in a case/control data set, suggesting that IgA-driven functions compromised immunity. These data highlight the interplay between IgG1, IgG3, and IgA, pointing to the need to profile the relationships between subclass/isotype selection.
Keywords	AIDS/HIV ; Vaccines ; Medicine ; R
Subject code	570
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: An observational study identifying highly tuberculosis-exposed, HIV-1-positive but persistently TB, tuberculin and IGRA negative persons with M. tuberculosis specific antibodies in Cape Town, South Africa

Elouise E. Kroon / Craig J. Kinnear / Marianna Orlova / Stephanie Fischinger / Sally Shin / Sihaam Boolay / Gerhard Walzl / Ashley Jacobs / Robert J. Wilkinson / Galit Alter / Erwin Schurr / Eileen G. Hoal / Marlo Möller

EBioMedicine, Vol 61, Iss , Pp 103053- (2020)

2020

Abstract: Background: Mycobacterium tuberculosis (Mtb) infection is inferred from positive results of T-cell immune conversion assays measuring Mtb-specific interferon gamma production or tuberculin skin test (TST) reactivity. Certain exposed individuals do not ... ...

Abstract	Background: Mycobacterium tuberculosis (Mtb) infection is inferred from positive results of T-cell immune conversion assays measuring Mtb-specific interferon gamma production or tuberculin skin test (TST) reactivity. Certain exposed individuals do not display T-cell immune conversion in these assays and do not develop TB. Here we report a hitherto unknown form of this phenotype: HIV-1-positive persistently TB, tuberculin and IGRA negative (HITTIN). Methods: A community-based case-control design was used to systematically screen and identify adults living with HIV (HIV+), aged 35–60 years, who met stringent study criteria, and then longitudinally followed up for repeat IGRA and TST testing. Participants had no history of TB despite living in TB hyper-endemic environments in Cape Town, South Africa with a provincial incidence of 681/100,000. Mtb-specific antibodies were measured using ELISA and Luminex. Findings: We identified 48/286 (17%) individuals who tested persistently negative for Mtb-specific T-cell immunoreactivity (three negative Quantiferon results and one TST = 0mm) over 206±154 days on average. Of these, 97·2% had documented CD4 counts<200 prior to antiretroviral therapy (ART). They had received ART for 7·0±3·0 years with a latest CD4 count of 505·8±191·4 cells/mm3. All HITTIN sent for further antibody testing (n=38) displayed Mtb-specific antibody titres. Interpretation: Immune reconstituted HIV+ persons can be persistently non-immunoreactive to TST and interferon-γ T-cell responses to Mtb, yet develop species-specific antibody responses. Exposure is evidenced by Mtb-specific antibody titres. Our identification of HIV+ individuals displaying a persisting lack of response to TST and IGRA T-cell immune conversion paves the way for future studies to investigate this phenotype in the context of HIV-infection that so far have received only scant attention.
Keywords	Resister ; Early clearance ; Interferon gamma release assay ; Tuberculin skin test ; Antibodies ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	570
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Sequence and vector shapes vaccine induced antibody effector functions in HIV vaccine trials.

Stephanie Fischinger / Deniz Cizmeci / Davy Deng / Shannon P Grant / Nicole Frahm / Julie McElrath / Jonathan Fuchs / Pierre-Alexandre Bart / Giuseppe Pantaleo / Michael Keefer / William O Hahn / Nadine Rouphael / Gavin Churchyard / Zoe Moodie / Yeycy Donastorg / Hendrik Streeck / Galit Alter

PLoS Pathogens, Vol 17, Iss 11, p e

2021 Volume 1010016

Abstract: Despite the advent of long-acting anti-retroviral therapy able to control and prevent infection, a preventative vaccine remains a global priority for the elimination of HIV. The moderately protective RV144 vaccine trial suggested functional IgG1 and IgG3 ...

Abstract	Despite the advent of long-acting anti-retroviral therapy able to control and prevent infection, a preventative vaccine remains a global priority for the elimination of HIV. The moderately protective RV144 vaccine trial suggested functional IgG1 and IgG3 antibodies were a potential correlate of protection, but the RV144-inspired HVTN702 validation trial failed to demonstrate efficacy despite inducing targeted levels of IgG1/IgG3. Alterations in inserts, and antigens, adjuvant, and regimen also resulted in vaccine induced target quantitative levels of the immune correlates, but drove qualitative changes to the humoral immune response, pointing to the urgent need to define the influence of vaccine strategies on shaping antibody quality, not just quantity. Thus, defining how distinct prime/boost approaches tune long-lived functional antibodies represents an important goal in vaccine development. Here, we compared vaccine responses in Phase I and II studies in humans utilizing various combinations of DNA/vector, vector/vector and DNA/protein HIV vaccines. We found that adenoviral vector immunization, compared to pox-viral vectors, resulted in the most potent IgG1 and IgG3 responses, linked to highly functional antibody activity, including assisting NK cell related functions. Minimal differences were observed in the durability of the functional humoral immune response across vaccine regimens, except for antibody dependent phagocytic function, which persisted for longer periods in the DNA/rAd5 and rAd35/rAd5 regimen, likely driven by higher IgG1 levels. Collectively, these findings suggest adenoviral vectors drive superior antibody quality and durability that could inform future clinical vaccine studies. Trial registration: ClinicalTrials.gov NCT00801697, NCT00961883, NCT02207920, NCT00125970, NCT02852005).
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comorbid illnesses are associated with altered adaptive immune responses to SARS-CoV-2

JCI Insight, Vol 6, Iss

2021 Volume 6

Abstract: Comorbid medical illnesses, such as obesity and diabetes, are associated with more severe COVID-19, hospitalization, and death. However, the role of the immune system in mediating these clinical outcomes has not been determined. We used multiparameter ... ...

Abstract	Comorbid medical illnesses, such as obesity and diabetes, are associated with more severe COVID-19, hospitalization, and death. However, the role of the immune system in mediating these clinical outcomes has not been determined. We used multiparameter flow cytometry and systems serology to comprehensively profile the functions of T cells and antibodies targeting spike, nucleocapsid, and envelope proteins in a convalescent cohort of COVID-19 subjects who were either hospitalized (n = 20) or not hospitalized (n = 40). To avoid confounding, subjects were matched by age, sex, ethnicity, and date of symptom onset. Surprisingly, we found that the magnitude and functional breadth of virus-specific CD4+ T cell and antibody responses were consistently higher among hospitalized subjects, particularly those with medical comorbidities. However, an integrated analysis identified more coordination between polyfunctional CD4+ T cells and antibodies targeting the S1 domain of spike among subjects who were not hospitalized. These data reveal a functionally diverse and coordinated response between T cells and antibodies targeting SARS-CoV-2, which is reduced in the presence of comorbid illnesses that are known risk factors for severe COVID-19.
Keywords	COVID-19 ; Immunology ; Medicine ; R
Subject code	616
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SARS-CoV-2 antibodies protect against reinfection for at least 6 months in a multicentre seroepidemiological workplace cohort.

Emilie Finch / Rachel Lowe / Stephanie Fischinger / Michael de St Aubin / Sameed M Siddiqui / Diana Dayal / Michael A Loesche / Justin Rhee / Samuel Beger / Yiyuan Hu / Matthew J Gluck / Benjamin Mormann / Mohammad A Hasdianda / Elon R Musk / Galit Alter / Anil S Menon / Eric J Nilles / Adam J Kucharski / CMMID COVID-19 working group and the SpaceX COVID-19 Cohort Collaborative

PLoS Biology, Vol 20, Iss 2, p e

2022 Volume 3001531

Abstract: Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states ... ...

Abstract	Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Persistence of viral RNA in lymph nodes in ART-suppressed SIV/SHIV-infected Rhesus Macaques

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 11

Abstract: The existence of HIV reservoir and ongoing replication despite antiretroviral therapy (ART) represents a barrier for cure efforts. Here, using SIV/SHIV-infected rhesus macaque suppressed with ART for one year, the authors characterize multiple lymphoid ... ...

Abstract	The existence of HIV reservoir and ongoing replication despite antiretroviral therapy (ART) represents a barrier for cure efforts. Here, using SIV/SHIV-infected rhesus macaque suppressed with ART for one year, the authors characterize multiple lymphoid and non-lymphoid tissues and show that while the viral reservoir exhibits a wide anatomic heterogeneity, persistent viral transcription is mainly restricted to secondary lymphoid organs.
Keywords	Science ; Q
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung

Nanda Kishore Routhu / Narayanaiah Cheedarla / Venkata Satish Bollimpelli / Sailaja Gangadhara / Venkata Viswanadh Edara / Lilin Lai / Anusmita Sahoo / Ayalnesh Shiferaw / Tiffany M. Styles / Katharine Floyd / Stephanie Fischinger / Caroline Atyeo / Sally A. Shin / Sanjeev Gumber / Shannon Kirejczyk / Kenneth H. Dinnon / Pei-Yong Shi / Vineet D. Menachery / Mark Tomai /

Christopher B. Fox / Galit Alter / Thomas H. Vanderford / Lisa Gralinski / Mehul S. Suthar / Rama Rao Amara

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 15

Abstract: Efficient vaccines for SARS-CoV-2 are needed. Here, the authors show that a trimeric form of the receptor-binding domain of SARS-CoV-2 spike adjuvanted with alum-3M-052 protects non-human primates from disease and inhibits infection. ...

Abstract	Efficient vaccines for SARS-CoV-2 are needed. Here, the authors show that a trimeric form of the receptor-binding domain of SARS-CoV-2 spike adjuvanted with alum-3M-052 protects non-human primates from disease and inhibits infection.
Keywords	Science ; Q
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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