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Article ; Online: A new way of identifying viral pathogens reactivating in cellular therapy products.

Cunningham, Anthony L / Micklethwaite, Kenneth

2024 Volume 102, Issue 3, Page(s) 153–155

Abstract: In this article, we discuss a recently published article that demonstrated a novel way of identifying viral pathogens reactivating in human cells to be used as cellular therapy, in this instance chimeric antigen receptor (CAR) T cells. The authors used ... ...

Abstract	In this article, we discuss a recently published article that demonstrated a novel way of identifying viral pathogens reactivating in human cells to be used as cellular therapy, in this instance chimeric antigen receptor (CAR) T cells. The authors used search engines and databases to identify viruses able to reactivate in T cells and then tested this initially in T-cell cultures, specifically human herpesvirus 6. This virus was then shown to reactivate infrequently in vitro and in vivo in CAR T cells as a consequence of T-cell activation. The methodology may be most clinically useful for more frequently reactivating viruses in other types of cellular therapy such as allogenic CAR T cells or induced pluripotent stem cells.
MeSH term(s)	Humans ; Cell Culture Techniques ; Lymphocyte Activation
Language	English
Publishing date	2024-01-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	284057-1
ISSN	1440-1711 ; 0818-9641
ISSN (online)	1440-1711
ISSN	0818-9641
DOI	10.1111/imcb.12724
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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

The Journal of clinical investigation

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: OMIP-096: A 24-color flow cytometry panel to identify and characterize CD4+ and CD8+ tissue-resident T cells in human skin, intestinal, and type II mucosal tissue.

O'Neil, Thomas R / Harman, Andrew N / Cunningham, Anthony L / Nasr, Najla / Bertram, Kirstie M

Cytometry. Part A : the journal of the International Society for Analytical Cytology

2023 Volume 103, Issue 11, Page(s) 851–856

Abstract: There is a great need to understand human immune cells within tissue, where disease manifests and infection occurs. Tissue-resident memory T cells (TRMs) were discovered over a decade ago, there is a great need to understand their role in human disease. ... ...

Abstract	There is a great need to understand human immune cells within tissue, where disease manifests and infection occurs. Tissue-resident memory T cells (TRMs) were discovered over a decade ago, there is a great need to understand their role in human disease. We developed a 24-color flow cytometry panel to comprehensively interrogate CD4
MeSH term(s)	Female ; Humans ; Flow Cytometry ; CD8-Positive T-Lymphocytes ; Intestines ; CD4-Positive T-Lymphocytes ; Mucous Membrane ; Immunologic Memory
Language	English
Publishing date	2023-09-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2099868-5
ISSN	1552-4930 ; 0196-4763 ; 1552-4922
ISSN (online)	1552-4930
ISSN	0196-4763 ; 1552-4922
DOI	10.1002/cyto.a.24782
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Zs.A 1688: Show issues			Location: 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: The herpes zoster subunit vaccine.

Cunningham, Anthony L

Expert opinion on biological therapy

2016 Volume 16, Issue 2, Page(s) 265–271

Abstract: Introduction: Herpes zoster (HZ) causes severe pain and rash in older people and may be complicated by prolonged pain (postherpetic neuralgia; PHN).: Areas covered: HZ results from reactivation of latent varicella-zoster virus (VZV) infection, often ... ...

Abstract	Introduction: Herpes zoster (HZ) causes severe pain and rash in older people and may be complicated by prolonged pain (postherpetic neuralgia; PHN). Areas covered: HZ results from reactivation of latent varicella-zoster virus (VZV) infection, often associated with age related or other causes of decreased T cell immunity. A concentrated live attenuated vaccine boosts this immunity and provides partial protection against HZ, but this decreases with age and declines over 5-8 years. The new HZ subunit (HZ/su or Shingrix) vaccine combines a key surface VZV glycoprotein (E) with T cell boosting adjuvant (AS01B). It is highly efficacious in protection (97%) against HZ in immunocompetent subjects, with no decline in advancing age and protection maintained for >3 years. Phase I-II trials showed safety and similar immunogenicity in severely immunocompromised patients. Local injection site pain and swelling can be severe in a minority (9.5%) but is transient (2 days). Expert opinion: The HZ/su vaccine appears very promising in immunocompetent patients in the ZoE-50 controlled trial. The unblinding of the current ZoE-50 trial and publication of results from the accompanying ZoE-70 trial will reveal more about its mechanism of action and its efficacy against PHN, particularly in subjects >70 years. Phase III trial results in immunocompromised patients are eagerly awaited.
MeSH term(s)	Adjuvants, Immunologic/therapeutic use ; Animals ; Herpes Zoster/diagnosis ; Herpes Zoster/immunology ; Herpes Zoster/prevention & control ; Herpes Zoster Vaccine/therapeutic use ; Herpesvirus 3, Human/immunology ; Humans ; Immunocompetence/immunology ; Neuralgia, Postherpetic/diagnosis ; Neuralgia, Postherpetic/immunology ; Neuralgia, Postherpetic/prevention & control ; Vaccines, Attenuated/therapeutic use ; Vaccines, Subunit/therapeutic use
Chemical Substances	Adjuvants, Immunologic ; Herpes Zoster Vaccine ; Vaccines, Attenuated ; Vaccines, Subunit
Language	English
Publishing date	2016
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2052501-1
ISSN	1744-7682 ; 1471-2598
ISSN (online)	1744-7682
ISSN	1471-2598
DOI	10.1517/14712598.2016.1134481
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Zs.A 6094: Show issues

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Article ; Online: Cytokines and chemokines: The vital role they play in herpes simplex virus mucosal immunology.

Smith, Jacinta B / Herbert, Jason J / Truong, Naomi R / Cunningham, Anthony L

Frontiers in immunology

2022 Volume 13, Page(s) 936235

Abstract: Herpes simplex viruses (HSV) types 1 and 2 are ubiquitous infections in humans. They cause orofacial and genital herpes with occasional severe complications. HSV2 also predisposes individuals to infection with HIV. There is currently no vaccine or ... ...

Abstract	Herpes simplex viruses (HSV) types 1 and 2 are ubiquitous infections in humans. They cause orofacial and genital herpes with occasional severe complications. HSV2 also predisposes individuals to infection with HIV. There is currently no vaccine or immunotherapy for these diseases. Understanding the immunopathogenesis of HSV infections is essential to progress towards these goals. Both HSV viruses result in initial infections in two major sites - in the skin or mucosa, either after initial infection or recurrence, and in the dorsal root or trigeminal ganglia where the viruses establish latency. HSV1 can also cause recurrent infection in the eye. At all of these sites immune cells respond to control infection. T cells and resident dendritic cells (DCs) in the skin/mucosa and around reactivating neurones in the ganglia, as well as keratinocytes in the skin and mucosa, are major sources of cytokines and chemokines. Cytokines such as the Type I and II interferons synergise in their local antiviral effects. Chemokines such as CCL2, 3 and 4 are found in lesion vesicle fluid, but their exact role in determining the interactions between epidermal and dermal DCs and with resident memory and infiltrating CD4 and CD8 T cells in the skin/mucosa is unclear. Even less is known about these mechanisms in the ganglia. Here we review the data on known sources and actions of these cytokines and chemokines at cellular and tissue level and indicate their potential for preventative and therapeutic interventions.
MeSH term(s)	Antiviral Agents ; Chemokines ; Cytokines ; Herpes Simplex ; Herpesvirus 1, Human ; Humans ; Interferons ; Mucous Membrane
Chemical Substances	Antiviral Agents ; Chemokines ; Cytokines ; Interferons (9008-11-1)
Language	English
Publishing date	2022-09-23
Publishing country	Switzerland
Document type	Journal Article ; Review ; 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.2022.936235
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Article ; Online: Defining the landscape of human epidermal mononuclear phagocytes.

Bertram, Kirstie M / O'Neil, Thomas R / Vine, Erica E / Baharlou, Heeva / Cunningham, Anthony L / Harman, Andrew N

Immunity

2023 Volume 56, Issue 3, Page(s) 459–460

MeSH term(s)	Humans ; Dendritic Cells ; Epidermis ; Skin ; Langerhans Cells ; Phagocytes
Language	English
Publishing date	2023-04-05
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2023.02.001
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Zs.A 4227: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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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 ; Online: Herpes Simplex Virus Type 1 Interactions with the Interferon System.

Danastas, Kevin / Miranda-Saksena, Monica / Cunningham, Anthony L

International journal of molecular sciences

2020 Volume 21, Issue 14

Abstract: The interferon (IFN) system is one of the first lines of defense activated against invading viral pathogens. Upon secretion, IFNs activate a signaling cascade resulting in the production of several interferon stimulated genes (ISGs), which work to limit ... ...

Abstract	The interferon (IFN) system is one of the first lines of defense activated against invading viral pathogens. Upon secretion, IFNs activate a signaling cascade resulting in the production of several interferon stimulated genes (ISGs), which work to limit viral replication and establish an overall anti-viral state. Herpes simplex virus type 1 is a ubiquitous human pathogen that has evolved to downregulate the IFN response and establish lifelong latent infection in sensory neurons of the host. This review will focus on the mechanisms by which the host innate immune system detects invading HSV-1 virions, the subsequent IFN response generated to limit viral infection, and the evasion strategies developed by HSV-1 to evade the immune system and establish latency in the host.
MeSH term(s)	Animals ; Herpes Simplex/immunology ; Herpesvirus 1, Human/genetics ; Herpesvirus 1, Human/metabolism ; Herpesvirus 1, Human/pathogenicity ; Host-Pathogen Interactions/immunology ; Humans ; Immunity, Innate ; Interferons/metabolism ; Signal Transduction/genetics ; Signal Transduction/immunology ; Toll-Like Receptors/immunology ; Virus Replication/genetics
Chemical Substances	Toll-Like Receptors ; Interferons (9008-11-1)
Language	English
Publishing date	2020-07-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21145150
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Article ; Online: Herpes Zoster Vaccines.

Cunningham, Anthony L / Levin, Myron J

The Journal of infectious diseases

2018 Volume 218, Issue suppl_2, Page(s) S127–S133

Abstract: Background: Immunization for herpes zoster (HZ) aims to reverse the decline in cell-mediated immunity to varicella zoster virus that occurs with advancing age or immunocompromise. There are 2 vaccines available, one live attenuated (Zoster vaccine, live ...

Abstract	Background: Immunization for herpes zoster (HZ) aims to reverse the decline in cell-mediated immunity to varicella zoster virus that occurs with advancing age or immunocompromise. There are 2 vaccines available, one live attenuated (Zoster vaccine, live attenuated [ZVL]) and, recently, a recombinant subunit vaccine (HZ/su). Methods: The literature relevant to the two HZ vaccines was reviewed. Results: ZVL has overall efficacies of 51% and 65% against HZ and postherpetic neuralgia, respectively, with a prominent decline in efficacy with advancing age of the vaccinee. This compares to approximately 90% efficacy against HZ for HZ/su that is minimally affected with advancing age. The efficacy of ZVL against HZ declines over 4 and 8 years, compared with minimal decline so far over 4 years with HZ/su, and immunogenicity that is maintained for 9 years. Local and systemic reactogenicity to HZ/su is much greater than to ZVL. Conclusions: HZ/su establishes an important principle-that a single recombinant viral protein with an effective adjuvant combination can stimulate immunogenicity superior to that of a live attenuated vaccine, and that this can diminish immunosenescence. This provides hope for improvement of other vaccines for aging patients. However, key questions remain unanswered, including the durability of the efficacy of HZ/su, its efficacy as a booster for previous recipients of ZVL, and its efficacy in immunocompromised patients.
MeSH term(s)	Herpes Zoster/prevention & control ; Herpes Zoster Vaccine/immunology ; Herpes Zoster Vaccine/standards ; Humans ; Protein Subunits ; Recombinant Proteins/immunology ; Vaccines, Inactivated ; Viral Proteins/immunology
Chemical Substances	Herpes Zoster Vaccine ; Protein Subunits ; Recombinant Proteins ; Vaccines, Inactivated ; Viral Proteins
Language	English
Publishing date	2018-10-23
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiy382
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Zs.MO 445: Show issues

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Article ; Online: Interferon inhibits the release of herpes simplex virus-1 from the axons of sensory neurons.

Danastas, Kevin / Guo, Gerry / Merjane, Jessica / Hong, Nathan / Larsen, Ava / Miranda-Saksena, Monica / Cunningham, Anthony L

mBio

2023 Volume 14, Issue 5, Page(s) e0181823

Abstract: Importance: Herpes simplex virus-1 (HSV-1) is a human pathogen known to cause cold sores and genital herpes. HSV-1 establishes lifelong infections in our sensory neurons, with no cure or vaccine available. HSV-1 can reactivate sporadically and travel ... ...

Abstract	Importance: Herpes simplex virus-1 (HSV-1) is a human pathogen known to cause cold sores and genital herpes. HSV-1 establishes lifelong infections in our sensory neurons, with no cure or vaccine available. HSV-1 can reactivate sporadically and travel back along sensory nerves, where it can form lesions in the oral and genital mucosa, eye, and skin, or be shed asymptomatically. New treatment options are needed as resistance is emerging to current antiviral therapies. Here, we show that interferons (IFNs) are capable of blocking virus release from nerve endings, potentially stopping HSV-1 transmission into the skin. Furthermore, we show that IFNγ has the potential to have widespread antiviral effects in the neuron and may have additional effects on HSV-1 reactivation. Together, this study identifies new targets for the development of immunotherapies to stop the spread of HSV-1 from the nerves into the skin.
MeSH term(s)	Humans ; Herpesvirus 1, Human/physiology ; Interferons ; Sensory Receptor Cells/pathology ; Axons/pathology ; Antiviral Agents ; Herpes Simplex
Chemical Substances	Interferons (9008-11-1) ; Antiviral Agents
Language	English
Publishing date	2023-09-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.01818-23
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