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Article: Cross-Reactive Immune Responses toward the Common Cold Human Coronaviruses and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Mini-Review and a Murine Study.

Sealy, Robert E / Hurwitz, Julia L

2021 Volume 9, Issue 8

Abstract: While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes serious morbidity and mortality in humans (coronavirus disease 2019, COVID-19), there is an enormous range of disease outcomes following virus exposures. Some individuals are ... ...

Abstract	While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes serious morbidity and mortality in humans (coronavirus disease 2019, COVID-19), there is an enormous range of disease outcomes following virus exposures. Some individuals are asymptomatic while others succumb to virus infection within days. Presently, the factors responsible for disease severity are not fully understood. One factor that may influence virus control is pre-existing immunity conferred by an individual's past exposures to common cold human coronaviruses (HCoVs). Here, we describe previous literature and a new, murine study designed to examine cross-reactive immune responses between SARS-CoV-2 and common cold HCoVs (represented by prototypes OC43, HKU1, 229E, and NL63). Experimental results have been mixed. In SARS-CoV-2-unexposed humans, cross-reactive serum antibodies were identified toward nucleocapsid (N) and the spike subunit S2. S2-specific antibodies were in some cases associated with neutralization. SARS-CoV-2-unexposed humans rarely exhibited antibody responses to the SARS-CoV-2 spike subunit S1, and when naïve mice were immunized with adjuvanted S1 from either SARS-CoV-2 or common cold HCoVs, S1-specific antibodies were poorly cross-reactive. When humans were naturally infected with SARS-CoV-2, cross-reactive antibodies that recognized common cold HCoV antigens increased in magnitude. Cross-reactive T cells, like antibodies, were present in humans prior to SARS-CoV-2 exposures and increased following SARS-CoV-2 infections. Some studies suggested that human infections with common cold HCoVs afforded protection against disease caused by subsequent exposures to SARS-CoV-2. Small animal models are now available for the testing of controlled SARS-CoV-2 infections. Additionally, in the United Kingdom, a program of SARS-CoV-2 human challenge experiments has received regulatory approval. Future, controlled experimental challenge studies may better define how pre-existing, cross-reactive immune responses influence SARS-CoV-2 infection outcomes.
Language	English
Publishing date	2021-07-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9081643
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Transient Global Amnesia.

Sealy, David / Tiller, Robert J / Johnson, Katherine

American family physician

2022 Volume 105, Issue 1, Page(s) 50–54

Abstract: Transient global amnesia (TGA) is a clinical syndrome characterized by anterograde amnesia, mild retrograde amnesia, and confusion up to 24 hours. Most commonly seen in patients older than 50 years, TGA results from the temporary impairment of short-term ...

Abstract	Transient global amnesia (TGA) is a clinical syndrome characterized by anterograde amnesia, mild retrograde amnesia, and confusion up to 24 hours. Most commonly seen in patients older than 50 years, TGA results from the temporary impairment of short-term memory formation. Clinically, patients have time disorientation and often ask repeated questions regarding the day's events. Vomiting, headache, blurry vision, dizziness, and nausea may be present. A physically or psychologically stressful precipitating event, such as emotional stress, significant physical exertion, exposure to extreme temperatures, high-altitude conditions, Valsalva maneuver, acute illness, or sexual intercourse, is often the cause. The pathophysiology of TGA is not well understood but may be related to impaired venous drainage of the hippocampus. The diagnosis is primarily clinical, but recent studies suggest that magnetic resonance imaging may be helpful. TGA is self-limited and resolves within 24 hours. There is no established treatment for episodes. The lifetime recurrence rate is 2.9% to 23.8%. Recent evidence suggests an association between TGA and migraine headaches as well as takotsubo cardiomyopathy. No apparent increased risk of cerebrovascular events occurs in patients who have had an episode of TGA. There is conflicting evidence as to whether an episode of TGA predisposes to future seizures or dementia.
MeSH term(s)	Adult ; Amnesia, Transient Global/diagnosis ; Amnesia, Transient Global/epidemiology ; Amnesia, Transient Global/physiopathology ; Coitus ; Confusion/epidemiology ; Female ; Hippocampus/physiopathology ; Humans ; Magnetic Resonance Imaging/methods ; Male ; Middle Aged ; Migraine Disorders/epidemiology ; Physical Exertion ; Risk Factors ; Stress, Psychological/epidemiology ; Takotsubo Cardiomyopathy/epidemiology ; Time Factors
Language	English
Publishing date	2022-01-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	412694-4
ISSN	1532-0650 ; 0002-838X ; 0572-3612
ISSN (online)	1532-0650
ISSN	0002-838X ; 0572-3612
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Article ; Online: Structure and Energetics of the Samarium Diiodide-HMPA Complex in Tetrahydrofuran.

Shotwell, J Brad / Sealy, Jennifer M / Flowers, Robert A

The Journal of organic chemistry

2021 Volume 64, Issue 14, Page(s) 5251–5255

Abstract: The role of HMPA as a ligand for ... ...

Abstract	The role of HMPA as a ligand for SmI
Language	English
Publishing date	2021-05-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	123490-0
ISSN	1520-6904 ; 0022-3263
ISSN (online)	1520-6904
ISSN	0022-3263
DOI	10.1021/jo990484l
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Article: Cross-Reactive Immune Responses toward the Common Cold Human Coronaviruses and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Mini-Review and a Murine Study

Sealy, Robert E. / Hurwitz, Julia L.

Microorganisms. 2021 July 31, v. 9, no. 8

2021

Abstract	While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes serious morbidity and mortality in humans (coronavirus disease 2019, COVID-19), there is an enormous range of disease outcomes following virus exposures. Some individuals are asymptomatic while others succumb to virus infection within days. Presently, the factors responsible for disease severity are not fully understood. One factor that may influence virus control is pre-existing immunity conferred by an individual’s past exposures to common cold human coronaviruses (HCoVs). Here, we describe previous literature and a new, murine study designed to examine cross-reactive immune responses between SARS-CoV-2 and common cold HCoVs (represented by prototypes OC43, HKU1, 229E, and NL63). Experimental results have been mixed. In SARS-CoV-2-unexposed humans, cross-reactive serum antibodies were identified toward nucleocapsid (N) and the spike subunit S2. S2-specific antibodies were in some cases associated with neutralization. SARS-CoV-2-unexposed humans rarely exhibited antibody responses to the SARS-CoV-2 spike subunit S1, and when naïve mice were immunized with adjuvanted S1 from either SARS-CoV-2 or common cold HCoVs, S1-specific antibodies were poorly cross-reactive. When humans were naturally infected with SARS-CoV-2, cross-reactive antibodies that recognized common cold HCoV antigens increased in magnitude. Cross-reactive T cells, like antibodies, were present in humans prior to SARS-CoV-2 exposures and increased following SARS-CoV-2 infections. Some studies suggested that human infections with common cold HCoVs afforded protection against disease caused by subsequent exposures to SARS-CoV-2. Small animal models are now available for the testing of controlled SARS-CoV-2 infections. Additionally, in the United Kingdom, a program of SARS-CoV-2 human challenge experiments has received regulatory approval. Future, controlled experimental challenge studies may better define how pre-existing, cross-reactive immune responses influence SARS-CoV-2 infection outcomes.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; animal models ; antibodies ; blood serum ; common cold ; disease severity ; humans ; morbidity ; mortality ; neutralization ; nucleocapsid ; viruses ; United Kingdom
Language	English
Dates of publication	2021-0731
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9081643
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Might Routine Vitamin A Monitoring in Cystic Fibrosis Patients Reduce Virus-Mediated Lung Pathology?

Sealy, Robert E / Surman, Sherri L / Vogel, Peter / Hurwitz, Julia L

Frontiers in immunology

2021 Volume 12, Page(s) 704391

Abstract: Cystic fibrosis (CF) is an autosomal recessive gene disorder that affects tens of thousands of patients worldwide. Individuals with CF often succumb to progressive lung disease and respiratory failure following recurrent infections with bacteria. Viral ... ...

Abstract	Cystic fibrosis (CF) is an autosomal recessive gene disorder that affects tens of thousands of patients worldwide. Individuals with CF often succumb to progressive lung disease and respiratory failure following recurrent infections with bacteria. Viral infections can also damage the lungs and heighten the CF patient's susceptibility to bacterial infections and long-term sequelae. Vitamin A is a key nutrient important for immune health and epithelial cell integrity, but there is currently no consensus as to whether vitamin A should be monitored in CF patients. Here we evaluate previous literature and present results from a CF mouse model, showing that oral vitamin A supplements significantly reduce lung lesions that would otherwise persist for 5-6 weeks post-virus exposure. Based on these results, we encourage continued research and suggest that programs for the routine monitoring and regulation of vitamin A levels may help reduce virus-induced lung pathology in CF patients.
MeSH term(s)	Animals ; Cystic Fibrosis/metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Dietary Supplements ; Disease Models, Animal ; Fatty Acid-Binding Proteins/genetics ; Humans ; Lung/pathology ; Lung/virology ; Mice ; Mice, Inbred CFTR ; Mice, Transgenic ; Promoter Regions, Genetic ; Respirovirus Infections/metabolism ; Sendai virus/physiology ; Vitamin A/administration & dosage ; Vitamin A/metabolism
Chemical Substances	CFTR protein, human ; FABP2 protein, human ; Fatty Acid-Binding Proteins ; Vitamin A (11103-57-4) ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6)
Language	English
Publishing date	2021-11-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.704391
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Article ; Online: Harnessing Natural Mosaics: Antibody-Instructed, Multi-Envelope HIV-1 Vaccine Design.

Sealy, Robert E / Dayton, Barry / Finkelstein, David / Hurwitz, Julia L

Viruses

2021 Volume 13, Issue 5

Abstract: The year 2021 marks the 40th anniversary since physicians recognized symptoms of the acquired immunodeficiency syndrome (AIDS), a disease that has since caused more than 30 million deaths worldwide. Despite the passing of four decades, there remains no ... ...

Abstract	The year 2021 marks the 40th anniversary since physicians recognized symptoms of the acquired immunodeficiency syndrome (AIDS), a disease that has since caused more than 30 million deaths worldwide. Despite the passing of four decades, there remains no licensed vaccine for the human immunodeficiency virus type 1 (HIV-1), the etiologic agent of AIDS. Despite the development of outstanding anti-retroviral drugs, there are currently more than one-half million deaths each year due to AIDS. Here, we revisit a conventional vaccine strategy used for protection against variable pathogens like HIV-1, which combines an array of diverse surface antigens. The strategy uses antibody recognition patterns to categorize viruses and their surface antigens into groups. Then a leader is assigned for each group and group leaders are formulated into vaccine cocktails. The group leaders are 'natural mosaics', because they share one or more epitope(s) with each of the other group members. We encourage the application of this conventional approach to HIV-1 vaccine design. We suggest that the partnering of an antibody-instructed envelope cocktail with new vaccine vectors will yield a successful vaccine in the HIV-1 field.
MeSH term(s)	AIDS Vaccines/immunology ; Animals ; Drug Design ; HIV Antibodies/immunology ; HIV Infections/immunology ; HIV Infections/prevention & control ; HIV Infections/virology ; HIV-1/drug effects ; HIV-1/genetics ; HIV-1/immunology ; Humans
Chemical Substances	AIDS Vaccines ; HIV Antibodies
Language	English
Publishing date	2021-05-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13050884
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Article ; Online: Short Communication: Parallel Analyses of Systemic and Local Vaccinations with Envelope Formulated in Adjuvant for Induction of HIV-Specific Antibodies in the Vaginal Mucosa.

Sealy, Robert E / Hurwitz, Julia L

AIDS research and human retroviruses

2017 Volume 33, Issue 5, Page(s) 424–427

Abstract: To prevent HIV-1 infections in females, vaccines that elicit antibodies in vaginal secretions are much desired. To induce these antibodies, intravaginal vaccinations are sometimes recommended. However, the benefit of intravaginal vaccination remains a ... ...

Abstract	To prevent HIV-1 infections in females, vaccines that elicit antibodies in vaginal secretions are much desired. To induce these antibodies, intravaginal vaccinations are sometimes recommended. However, the benefit of intravaginal vaccination remains a topic of debate, and parallel studies of intravaginal and intramuscular vaccination routes are rarely performed. Here we describe tests of mucosal and systemic antibodies after mouse vaccinations by several routes with HIV-1 envelope protein formulated in adjuvant. Response magnitudes were as follows: intraperitoneal > intramuscular = intravaginal tissue ≥ subcutaneous. We found that the well-accepted and logistically feasible intramuscular immunization was similar to intravaginal tissue immunization for the induction of antibodies in blood and vaginal secretions. Results suggest that a routine comparison of intravaginal and intramuscular immunizations may serve as a beneficial gatekeeper for the development of new intravaginal HIV-1 vaccines.
Language	English
Publishing date	2017-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	639130-8
ISSN	1931-8405 ; 0889-2229
ISSN (online)	1931-8405
ISSN	0889-2229
DOI	10.1089/AID.2016.0218
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Article: Harnessing Natural Mosaics: Antibody-Instructed, Multi-Envelope HIV-1 Vaccine Design

Sealy, Robert E / Dayton, Barry / Finkelstein, David / Hurwitz, Julia L

Viruses. 2021 May 11, v. 13, no. 5

2021

Abstract	The year 2021 marks the 40th anniversary since physicians recognized symptoms of the acquired immunodeficiency syndrome (AIDS), a disease that has since caused more than 30 million deaths worldwide. Despite the passing of four decades, there remains no licensed vaccine for the human immunodeficiency virus type 1 (HIV-1), the etiologic agent of AIDS. Despite the development of outstanding anti-retroviral drugs, there are currently more than one-half million deaths each year due to AIDS. Here, we revisit a conventional vaccine strategy used for protection against variable pathogens like HIV-1, which combines an array of diverse surface antigens. The strategy uses antibody recognition patterns to categorize viruses and their surface antigens into groups. Then a leader is assigned for each group and group leaders are formulated into vaccine cocktails. The group leaders are ‘natural mosaics’, because they share one or more epitope(s) with each of the other group members. We encourage the application of this conventional approach to HIV-1 vaccine design. We suggest that the partnering of an antibody-instructed envelope cocktail with new vaccine vectors will yield a successful vaccine in the HIV-1 field.
Keywords	Human immunodeficiency virus 1 ; acquired immunodeficiency syndrome ; antibodies ; antiretroviral agents ; epitopes ; vaccine development ; vaccines
Language	English
Dates of publication	2021-0511
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13050884
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Community-based Systems Dynamics for Reproductive Health: An Example from Urban Ohio.

Hyder, Ayaz / Smith, Mikaela / Sealy-Jefferson, Shawnita / Hood, Robert B / Chettri, Shibani / Dundon, Ashley / Underwood, Abigail / Bessett, Danielle / Norris, Alison H

Progress in community health partnerships : research, education, and action

2022 Volume 16, Issue 3, Page(s) 361–383

Abstract: Background: Health outcomes, risk factors, and policies are complexly related to the reproductive health system. Systems-level frameworks for understanding and acting within communities through community-engaged research are needed to mitigate adverse ... ...

Abstract	Background: Health outcomes, risk factors, and policies are complexly related to the reproductive health system. Systems-level frameworks for understanding and acting within communities through community-engaged research are needed to mitigate adverse reproductive health outcomes more effectively within the community. Objectives: To describe and share lessons learned from an ongoing application of a participatory modeling approach (community-based system dynamics) that aims to eliminate racial inequities in Black-White reproductive health outcomes. Methods: The community-based system dynamics approach involves conducting complementary activities, workshops, modeling, and dissemination. We organized workshops, co-developed a causal loop diagram of the reproductive health system with participants from the community, and created materials to disseminate workshop findings and preliminary models. Lessons learned: Many opportunities exist for cross-fertilization of best practices between community-based system dynamics and community-based participatory research. Shared learning environments offer benefits for modelers and domain experts alike. Additionally, identifying local champions from the community helps manage group dynamics. Conclusions: Community-based system dynamics is well-suited for understanding complexity in the reproductive health system. It allows participants from diverse perspectives to identify strategies to eliminate racial inequities in reproductive health outcomes.
MeSH term(s)	Community-Based Participatory Research ; Humans ; Ohio ; Reproductive Health
Language	English
Publishing date	2022-08-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2275483-0
ISSN	1557-055X ; 1557-0541
ISSN (online)	1557-055X
ISSN	1557-0541
DOI	10.1353/cpr.2022.0053
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Retinol Binding Protein, Sunlight Hours, and the Influenza Virus-Specific Immune Response.

Patel, Nehali / Penkert, Rhiannon R / Sealy, Robert E / Surman, Sherri L / Jones, Bart G / Ringwald-Smith, Karen / Ross, A Catharine / Hurwitz, Julia L

Biomedicines

2022 Volume 10, Issue 9

Abstract: Healthy pediatric immune responses depend on adequate vitamin A and D levels. Relationships between solar ultraviolet B (UVB) radiation and vitamin D are well understood, while relationships between sunlight, vitamin A, and its serum escort, retinol ... ...

Abstract	Healthy pediatric immune responses depend on adequate vitamin A and D levels. Relationships between solar ultraviolet B (UVB) radiation and vitamin D are well understood, while relationships between sunlight, vitamin A, and its serum escort, retinol binding protein (RBP), are not. A pediatric clinical study enrolled 2-8-year-old children at various times between September 2016 and March 2017, inclusive, in Memphis, Tennessee. A serum sample from each child was then assayed to examine the influence of season on vitamin levels. We found that RBP and RBP/retinol molar ratios decreased in winter months and RBP/retinol ratios correlated positively with the average daily sunlight hours per month. A food frequency questionnaire given to parents/guardians indicated a shift in dietary intake from plant-based foods to animal-based foods by children between winter and spring months. This translated to higher retinol and zinc (integral to RBP-transthyretin-retinol complexes) in the spring, perhaps explaining the seasonal influence on RBP/retinol. RBP and retinol were associated positively with IgG/IgM and IgA/IgM ratios. RBP and retinol, but not 25(OH)D, also correlated positively with influenza virus-specific antibodies. Retinol correlated negatively, while 25(OH)D correlated positively, with certain serum cytokine/chemokine levels. Significant differences in 25(OH)D, immunoglobulin ratios, and cytokines/chemokines were observed between black and white children. In sum, seasonal changes in dietary foods rich in retinol and zinc may have influenced RBP levels, which in turn influenced innate and adaptive immune responses. Results encourage routine monitoring and reporting of season, RBP, and vitamin levels in future clinical studies, as seasons may affect sunlight exposures, diet, vitamin levels, and immune protection against infectious disease.
Language	English
Publishing date	2022-09-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10092322
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