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Article ; Online: Advances in understanding the mechanism of action of adult vaccines.

Cunningham, Anthony L / Sandgren, Kerrie J / Truong, Naomi R

2023 Volume 133, Issue 23

Abstract: The occurrence of herpes zoster (HZ) correlates with declining memory T cells that had responded to earlier infection with varicella-zoster virus (VZV). There are especially lower T cell responses to the single immunodominant VZV protein glycoprotein E ( ... ...

Abstract	The occurrence of herpes zoster (HZ) correlates with declining memory T cells that had responded to earlier infection with varicella-zoster virus (VZV). There are especially lower T cell responses to the single immunodominant VZV protein glycoprotein E (gE) in people over 50 years of age, although antibody responses to VZV persist. Therefore, a live attenuated zoster vaccine (ZVL) aimed at restoring T cell responses was developed. Surprisingly, a recombinant zoster vaccine (RZV) consisting of gE combined with the AS01B adjuvant system proved superior in efficacy and durability. In this issue of the JCI, Laing, Ford, and colleagues showed that both vaccines stimulated preimmunization naive CD4+ T cells, not just memory CD4+ T cells, to gE, and recruited these naive responses into the overall memory response. However, compared with ZVL, RZV stimulated this response to a much greater degree. These results will help guide development of more effective and durable vaccines for older individuals.
MeSH term(s)	Humans ; Adult ; Middle Aged ; Herpes Zoster Vaccine ; Herpes Zoster/prevention & control ; Herpesvirus 3, Human ; CD4-Positive T-Lymphocytes ; Vaccines, Synthetic ; Vaccines, Attenuated
Chemical Substances	Herpes Zoster Vaccine ; Vaccines, Synthetic ; Vaccines, Attenuated
Language	English
Publishing date	2023-12-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI175378
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Article ; Online: Tissue resident memory T cells inhabit the deep human conjunctiva.

Arnous, Racha / Arshad, Sana / Sandgren, Kerrie / Cunningham, Anthony L / Carnt, Nicole / White, Andrew

Scientific reports

2022 Volume 12, Issue 1, Page(s) 6077

Abstract: Mucosal linings of the body, including the conjunctiva, are enriched in tissue-resident memory T cells ( ... ...

Abstract	Mucosal linings of the body, including the conjunctiva, are enriched in tissue-resident memory T cells (T
MeSH term(s)	Adult ; Aged ; CD8-Positive T-Lymphocytes ; Conjunctiva ; Epithelium ; Female ; Humans ; Immunologic Memory ; Memory T Cells ; Middle Aged ; Mucous Membrane
Language	English
Publishing date	2022-04-12
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/s41598-022-09886-3
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Article: CTI special feature on innate immune responses and vaccine design.

Sundling, Christopher / Sandgren, Kerrie

Clinical & translational immunology

2016 Volume 5, Issue 8, Page(s) e96

Language	English
Publishing date	2016-08-12
Publishing country	Australia
Document type	Editorial
ZDB-ID	2694482-0
ISSN	2050-0068
ISSN	2050-0068
DOI	10.1038/cti.2016.50
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Article ; Online: Mechanisms of Immune Control of Mucosal HSV Infection: A Guide to Rational Vaccine Design.

Truong, Naomi R / Smith, Jacinta B / Sandgren, Kerrie J / Cunningham, Anthony L

Frontiers in immunology

2019 Volume 10, Page(s) 373

Abstract: Herpes Simplex Virus (HSV) is a highly prevalent sexually transmitted infection that aside from causing cold sores and genital lesions, causes complications in the immunocompromised and has facilitated a large proportion of HIV acquisition globally. ... ...

Abstract	Herpes Simplex Virus (HSV) is a highly prevalent sexually transmitted infection that aside from causing cold sores and genital lesions, causes complications in the immunocompromised and has facilitated a large proportion of HIV acquisition globally. Despite decades of research, there is no prophylactic HSV vaccine ready for use in humans, leaving many questioning whether a prophylactic vaccine is an achievable goal. A previous HSV vaccine trial did have partial success in decreasing acquisition of HSV2-promising evidence that vaccines can prevent acquisition. However, there is still an incomplete understanding of the immune response pathways elicited by HSV after initial mucosal infection and how best to replicate these responses with a vaccine, such that acquisition and colonization of the dorsal root ganglia could be prevented. Another factor to consider in the rational design of an HSV vaccine is adjuvant choice. Understanding the immune responses elicited by different adjuvants and whether lasting humoral and cell-mediated responses are induced is important, especially when studies of past trial vaccines found that a sufficiently protective cell-mediated response was lacking. In this review, we discuss what is known of the immune control involved in initial herpes lesions and reactivation, including the importance of CD4 and CD8 T cells, and the interplay between innate and adaptive immunity in response to primary infection, specifically focusing on the viral relay involved. Additionally, a summary of previous and current vaccine trials, including the components used, immune responses elicited and the feasibility of prophylactic vaccines looking forward, will also be discussed.
MeSH term(s)	Antibodies, Viral/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/pathology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/pathology ; Ganglia, Spinal/immunology ; Ganglia, Spinal/pathology ; Ganglia, Spinal/virology ; Herpes Simplex/immunology ; Herpes Simplex/pathology ; Herpes Simplex/prevention & control ; Herpesvirus 2, Human/immunology ; Herpesvirus Vaccines/immunology ; Herpesvirus Vaccines/therapeutic use ; Humans ; Immunity, Cellular ; Immunity, Mucosal
Chemical Substances	Antibodies, Viral ; Herpesvirus Vaccines
Language	English
Publishing date	2019-03-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2019.00373
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Article: Understanding natural herpes simplex virus immunity to inform next-generation vaccine design.

Sandgren, Kerrie J / Bertram, Kirstie / Cunningham, Anthony L

Clinical & translational immunology

2016 Volume 5, Issue 7, Page(s) e94

Abstract: Incremental advances in our knowledge of how natural immune control of herpes simplex virus (HSV) develops have yielded insight as to why previous vaccine attempts have only been partially successful, however, our understanding of these pathways, ... ...

Abstract	Incremental advances in our knowledge of how natural immune control of herpes simplex virus (HSV) develops have yielded insight as to why previous vaccine attempts have only been partially successful, however, our understanding of these pathways, particularly in humans, is still incomplete. Further elucidation of the innate immune events that are responsible for stimulating these effector responses is required to accurately inform vaccine design. An enhanced understanding of the mechanism of action of novel adjuvants will also facilitate the rational choice of adjuvant to optimise such responses. Here we review the reasons for the hitherto partial HSV vaccine success and align these with our current knowledge of how natural HSV immunity develops. In particular, we focus on the innate immune response and the role of dendritic cells in inducing protective T-cell responses and how these pathways might be recapitulated in a vaccine setting.
Language	English
Publishing date	2016-07-29
Publishing country	Australia
Document type	Journal Article ; Review
ZDB-ID	2694482-0
ISSN	2050-0068
ISSN	2050-0068
DOI	10.1038/cti.2016.44
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Article ; Online: Vaccines for Herpes Simplex: Recent Progress Driven by Viral and Adjuvant Immunology.

Sandgren, Kerrie J / Truong, Naomi R / Smith, Jacinta B / Bertram, Kirstie / Cunningham, Anthony L

Methods in molecular biology (Clifton, N.J.)

2019 Volume 2060, Page(s) 31–56

Abstract: Herpes simplex viruses (HSV) types 1 and 2 are ubiquitous. They both cause genital herpes, occasionally severe disease in the immunocompromised, and facilitate much HIV acquisition globally. Despite more than 60 years of research, there is no licensed ... ...

Abstract	Herpes simplex viruses (HSV) types 1 and 2 are ubiquitous. They both cause genital herpes, occasionally severe disease in the immunocompromised, and facilitate much HIV acquisition globally. Despite more than 60 years of research, there is no licensed prophylactic HSV vaccine and some doubt as to whether this can be achieved. Nevertheless, a previous HSV vaccine candidate did have partial success in preventing genital herpes and HSV acquisition and another immunotherapeutic candidate reduced viral shedding and recurrent lesions, inspiring further research. However, the entry pathway of HSV into the anogenital mucosa and the subsequent cascade of immune responses need further elucidation so that these responses could be mimicked or improved by a vaccine, to prevent viral entry and colonization of the neuronal ganglia. For an effective novel vaccine against genital herpes the choice of antigen and adjuvant may be critical. The incorporation of adjuvants of the vaccine candidates in the past, may account for their partial efficacy. It is likely that they can be improved by understanding the mechanisms of immune responses elicited by different adjuvants and comparing these to natural immune responses. Here we review the history of vaccines for HSV, those in development and compare them to successful vaccines for chicken pox or herpes zoster. We also review what is known of the natural immune control of herpes lesions, via interacting innate immunity and CD4 and CD8 T cells and the lessons they provide for development of new, more effective vaccines.
MeSH term(s)	Adjuvants, Immunologic/therapeutic use ; Animals ; Herpes Genitalis/immunology ; Herpes Genitalis/pathology ; Herpes Genitalis/prevention & control ; Herpes Simplex/immunology ; Herpes Simplex/pathology ; Herpes Simplex/prevention & control ; Herpes Simplex Virus Vaccines/immunology ; Herpes Simplex Virus Vaccines/therapeutic use ; Herpesvirus 1, Human/immunology ; Herpesvirus 2, Human/immunology ; Humans
Chemical Substances	Adjuvants, Immunologic ; Herpes Simplex Virus Vaccines
Language	English
Publishing date	2019-10-15
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-9814-2_2
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Article ; Online: Highly Networked SARS-CoV-2 Peptides Elicit T Cell Responses with Enhanced Specificity.

Duette, Gabriel / Lee, Eunok / Martins Costa Gomes, Gabriela / Tungatt, Katie / Doyle, Chloe / Stylianou, Vicki V / Lee, Ashley / Maddocks, Susan / Taylor, Janette / Khanna, Rajiv / Bull, Rowena A / Martinello, Marianne / Sandgren, Kerrie J / Cunningham, Anthony L / Palmer, Sarah

ImmunoHorizons

2023 Volume 7, Issue 6, Page(s) 508–527

Abstract: Identifying SARS-CoV-2-specific T cell epitope-derived peptides is critical for the development of effective vaccines and measuring the duration of specific SARS-CoV-2 cellular immunity. In this regard, we previously identified T cell epitope-derived ... ...

Abstract	Identifying SARS-CoV-2-specific T cell epitope-derived peptides is critical for the development of effective vaccines and measuring the duration of specific SARS-CoV-2 cellular immunity. In this regard, we previously identified T cell epitope-derived peptides within topologically and structurally essential regions of SARS-CoV-2 spike and nucleocapsid proteins by applying an immunoinformatics pipeline. In this study, we selected 30 spike- and nucleocapsid-derived peptides and assessed whether these peptides induce T cell responses and avoid major mutations found in SARS-CoV-2 variants of concern. Our peptide pool was highly specific, with only a single peptide driving cross-reactivity in people unexposed to SARS-COV-2, and immunogenic, inducing a polyfunctional response in CD4+ and CD8+ T cells from COVID-19 recovered individuals. All peptides were immunogenic and individuals recognized broad and diverse peptide repertoires. Moreover, our peptides avoided most mutations/deletions associated with all four SARS-CoV-2 variants of concern while retaining their physicochemical properties even when genetic changes are introduced. This study contributes to an evolving definition of individual CD4+ and CD8+ T cell epitopes that can be used for specific diagnostic tools for SARS-CoV-2 T cell responses and is relevant to the development of variant-resistant and durable T cell-stimulating vaccines.
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19 ; Epitopes, T-Lymphocyte ; Peptides
Chemical Substances	Epitopes, T-Lymphocyte ; Peptides
Language	English
Publishing date	2023-06-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2573-7732
ISSN (online)	2573-7732
DOI	10.4049/immunohorizons.2300034
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Article ; Online: AFid: a tool for automated identification and exclusion of autofluorescent objects from microscopy images.

Baharlou, Heeva / Canete, Nicolas P / Bertram, Kirstie M / Sandgren, Kerrie J / Cunningham, Anthony L / Harman, Andrew N / Patrick, Ellis

Bioinformatics (Oxford, England)

2020 Volume 37, Issue 4, Page(s) 559–567

Abstract: Motivation: Autofluorescence is a long-standing problem that has hindered the analysis of images of tissues acquired by fluorescence microscopy. Current approaches to mitigate autofluorescence in tissue are lab-based and involve either chemical ... ...

Abstract	Motivation: Autofluorescence is a long-standing problem that has hindered the analysis of images of tissues acquired by fluorescence microscopy. Current approaches to mitigate autofluorescence in tissue are lab-based and involve either chemical treatment of sections or specialized instrumentation and software to 'unmix' autofluorescent signals. Importantly, these approaches are pre-emptive and there are currently no methods to deal with autofluorescence in acquired fluorescence microscopy images. Results: To address this, we developed Autofluorescence Identifier (AFid). AFid identifies autofluorescent pixels as discrete objects in multi-channel images post-acquisition. These objects can then be tagged for exclusion from downstream analysis. We validated AFid using images of FFPE human colorectal tissue stained for common immune markers. Further, we demonstrate its utility for image analysis where its implementation allows the accurate measurement of HIV-Dendritic cell interactions in a colorectal explant model of HIV transmission. Therefore, AFid represents a major leap forward in the extraction of useful data from images plagued by autofluorescence by offering an approach that is easily incorporated into existing workflows and that can be used with various samples, staining panels and image acquisition methods. We have implemented AFid in ImageJ, Matlab and R to accommodate the diverse image analysis community. Availability and implementation: AFid software is available at https://ellispatrick.github.io/AFid. Supplementary information: Supplementary data are available at Bioinformatics online.
MeSH term(s)	Histological Techniques ; Humans ; Image Processing, Computer-Assisted ; Microscopy, Fluorescence ; Software ; Workflow
Language	English
Publishing date	2020-10-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btaa780
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Article ; Online: Identification of SARS-CoV-2 Nucleocapsid and Spike T-Cell Epitopes for Assessing T-Cell Immunity.

Lee, Eunok / Sandgren, Kerrie / Duette, Gabriel / Stylianou, Vicki V / Khanna, Rajiv / Eden, John-Sebastian / Blyth, Emily / Gottlieb, David / Cunningham, Anthony L / Palmer, Sarah

Journal of virology

2021 Volume 95, Issue 6

Abstract: Developing optimal T-cell response assays to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is critical for measuring the duration of immunity to this disease and assessing the efficacy of vaccine candidates. These assays need to ... ...

Abstract	Developing optimal T-cell response assays to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is critical for measuring the duration of immunity to this disease and assessing the efficacy of vaccine candidates. These assays need to target conserved regions of SARS-CoV-2 global variants and avoid cross-reactivity to seasonal human coronaviruses. To contribute to this effort, we employed an
MeSH term(s)	Amino Acid Sequence ; Antigen Presentation ; CD8-Positive T-Lymphocytes/immunology ; COVID-19/blood ; COVID-19/immunology ; Computational Biology ; Coronavirus/classification ; Coronavirus/immunology ; Coronavirus Nucleocapsid Proteins/chemistry ; Coronavirus Nucleocapsid Proteins/genetics ; Coronavirus Nucleocapsid Proteins/immunology ; Epitopes, T-Lymphocyte/chemistry ; Epitopes, T-Lymphocyte/genetics ; Epitopes, T-Lymphocyte/immunology ; HLA Antigens/immunology ; Humans ; Immunity, Cellular ; Mutation ; Phosphoproteins/chemistry ; Phosphoproteins/genetics ; Phosphoproteins/immunology ; Protein Binding ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; Species Specificity ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/immunology
Chemical Substances	Coronavirus Nucleocapsid Proteins ; Epitopes, T-Lymphocyte ; HLA Antigens ; Phosphoproteins ; Spike Glycoprotein, Coronavirus ; nucleocapsid phosphoprotein, SARS-CoV-2 ; spike protein, SARS-CoV-2
Language	English
Publishing date	2021-02-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.02002-20
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Article ; Online: Multiple COVID-19 vaccine doses in CLL and MBL improve immune responses with progressive and high seroconversion.

Shen, Yandong / Freeman, Jane A / Holland, Juliette / Naidu, Kartik / Solterbeck, Ann / Van Bilsen, Nenna / Downe, Paul / Kerridge, Ian / Wallman, Lucinda / Akerman, Anouschka / Aggarwal, Anupriya / Milogiannakis, Vanessa / Martins Costa Gomes, Gabriela / Doyle, Chloe M / Sandgren, Kerrie J / Turville, Stuart / Cunningham, Anthony L / Mulligan, Stephen P

Blood

2022 Volume 140, Issue 25, Page(s) 2709–2721

Abstract: Patients with chronic lymphocytic leukemia (CLL) or monoclonal B-lymphocytosis (MBL) have impaired response to COVID-19 vaccination. A total of 258 patients (215 with CLL and 43 with MBL) had antispike antibody levels evaluable for statistical analysis. ... ...

Abstract	Patients with chronic lymphocytic leukemia (CLL) or monoclonal B-lymphocytosis (MBL) have impaired response to COVID-19 vaccination. A total of 258 patients (215 with CLL and 43 with MBL) had antispike antibody levels evaluable for statistical analysis. The overall seroconversion rate in patients with CLL was 94.2% (antispike antibodies ≥50 AU/mL) and 100% in patients with MBL after multiple vaccine doses. After 3 doses (post-D3) in 167 patients with CLL, 73.7% were seropositive, 17.4% had antispike antibody levels between 50 and 999 AU/mL, and 56.3% had antispike antibody levels ≥1000 AU/mL, with a median rise from 144.6 to 1800.7 AU/mL. Of patients who were seronegative post-D2, 39.7% seroconverted post-D3. For those who then remained seronegative after their previous dose, seroconversion occurred in 40.6% post-D4, 46.2% post-D5, 16.7% post-D6, and 0% after D7 or D8. After seroconversion, most had a progressive increase in antispike antibody levels. Neutralization was associated with higher antispike antibody levels, more vaccine doses, and earlier severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants; neutralizing antibody against early clade D614G was detected in 65.3%, against Delta in 52.0%, and against Omicron in 36.5%. SARS-CoV-2-specific T-cell production of interferon γ and interleukin 2 occurred in 73.9% and 60.9%, respectively, of 23 patients tested. After multiple vaccine doses, by multivariate analysis, immunoglobulin M ≥0.53 g/L, immunoglobulin subclass G3 ≥0.22 g/L and absence of current CLL therapy were independent predictors of positive serological responses. Multiple sequential COVID-19 vaccination significantly increased seroconversion and antispike antibody levels in patients with CLL or MBL.
MeSH term(s)	Humans ; COVID-19 Vaccines ; Leukemia, Lymphocytic, Chronic, B-Cell/therapy ; Lymphocytosis ; Seroconversion ; COVID-19/prevention & control ; SARS-CoV-2 ; Immunoglobulin M ; Immunoglobulin G ; Immunity ; Antibodies, Viral
Chemical Substances	COVID-19 Vaccines ; Immunoglobulin M ; Immunoglobulin G ; Antibodies, Viral
Language	English
Publishing date	2022-10-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022017814
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