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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: 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: 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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Article ; Online: Seasonal quadrivalent mRNA vaccine prevents and mitigates influenza infection.

Kackos, Christina M / DeBeauchamp, Jennifer / Davitt, Christopher J H / Lonzaric, Jan / Sealy, Robert E / Hurwitz, Julia L / Samsa, Marcelo M / Webby, Richard J

NPJ vaccines

2023 Volume 8, Issue 1, Page(s) 157

Abstract: Annually, seasonal influenza is responsible for millions of infections and hundreds of thousands of deaths. The current method for managing influenza is vaccination using a standardized amount of the influenza virus' primary surface antigen, ... ...

Abstract	Annually, seasonal influenza is responsible for millions of infections and hundreds of thousands of deaths. The current method for managing influenza is vaccination using a standardized amount of the influenza virus' primary surface antigen, hemagglutinin (HA), as the intended target of the immune response. This vaccination strategy results in vaccines with variable efficacy year to year due to antigenic drift of HA, which can be further exacerbated by manufacturing processes optimizing growth of vaccine virus in eggs. Due to these limitations, alternative vaccine platforms are actively being explored to improve influenza vaccine efficacy, including cell-based, recombinant protein, and mRNA vaccines. mRNA's rapid, in vitro production makes it an appealing platform for influenza vaccination, and the success of SARS-CoV-2 mRNA vaccines in the clinic has encouraged the development of mRNA vaccines for other pathogens. Here, the immunogenicity and protective efficacy of a quadrivalent mRNA vaccine encoding HA from four seasonal influenza viruses, A/California/07/2009 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008 (B-Victoria lineage), and B/Phuket/3073/2013 (B-Yamagata lineage), was evaluated. In mice, a 120 μg total dose of this quadrivalent mRNA vaccine induced robust antibody titers against each subtype that were commensurate with titers when each antigen was administered alone. Following A/California/04/2009 challenge, mice were fully protected from morbidity and mortality, even at doses as low as 1 μg of each antigen. Additionally, a single administration of 10 μg of quadrivalent mRNA was sufficient to prevent weight loss caused by A/California/04/2009. These results support the promise of this mRNA vaccine for prevention and mitigation of influenza vaccine.
Language	English
Publishing date	2023-10-12
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-023-00752-5
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Article ; Online: CD4

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

Vaccine

2017 Volume 35, Issue 20, Page(s) 2617–2621

Abstract: The RSV vaccine field suffered a major set-back when children were vaccinated with a formalin-inactivated RSV vaccine (FI-RSV). Unexpectedly, the vaccinated children fared worse than unvaccinated children when they were naturally infected with RSV. Mouse ...

Abstract	The RSV vaccine field suffered a major set-back when children were vaccinated with a formalin-inactivated RSV vaccine (FI-RSV). Unexpectedly, the vaccinated children fared worse than unvaccinated children when they were naturally infected with RSV. Mouse models were then developed that implicated the CD4
Language	English
Publishing date	2017-05-09
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2017.03.073
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Article ; Online: The influences of microbial colonisation and germ-free status on the chicken TCRβ repertoire.

Dascalu, Stefan / Preston, Stephen G / Dixon, Robert J / Flammer, Patrik G / Fiddaman, Steven / Boyd, Amy / Sealy, Joshua E / Sadeyen, Jean-Remy / Kaspers, Bernd / Velge, Philippe / Iqbal, Munir / Bonsall, Michael B / Smith, Adrian L

Frontiers in immunology

2023 Volume 13, Page(s) 1052297

Abstract: Microbial colonisation is paramount to the normal development of the immune system, particularly at mucosal sites. However, the relationships between the microbiome and the adaptive immune repertoire have mostly been explored in rodents and humans. Here, ...

Abstract	Microbial colonisation is paramount to the normal development of the immune system, particularly at mucosal sites. However, the relationships between the microbiome and the adaptive immune repertoire have mostly been explored in rodents and humans. Here, we report a high-throughput sequencing analysis of the chicken TCRβ repertoire and the influences of microbial colonisation on tissue-resident TCRβ+ cells. The results reveal that the microbiome is an important driver of TCRβ diversity in both intestinal tissues and the bursa of Fabricius, but not in the spleen. Of note, public TCRβ sequences (shared across individuals) make a substantial contribution to the repertoire. Additionally, different tissues exhibit biases in terms of their V family and J gene usage, and these effects were influenced by the gut-associated microbiome. TCRβ clonal expansions were identified in both colonised and germ-free birds, but differences between the groups were indicative of an influence of the microbiota. Together, these findings provide an insight into the avian adaptive immune system and the influence of the microbiota on the TCRβ repertoire.
MeSH term(s)	Humans ; Animals ; Chickens ; Immune System ; Intestines
Language	English
Publishing date	2023-01-04
Publishing country	Switzerland
Document type	Journal Article ; 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.2022.1052297
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