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  1. Article ; Online: Can T Cells Abort SARS-CoV-2 and Other Viral Infections?

    Swadling, Leo / Maini, Mala K

    International journal of molecular sciences

    2023  Volume 24, Issue 5

    Abstract: Despite the highly infectious nature of the SARS-CoV-2 virus, it is clear that some individuals with potential exposure, or even experimental challenge with the virus, resist developing a detectable infection. While a proportion of seronegative ... ...

    Abstract Despite the highly infectious nature of the SARS-CoV-2 virus, it is clear that some individuals with potential exposure, or even experimental challenge with the virus, resist developing a detectable infection. While a proportion of seronegative individuals will have completely avoided exposure to the virus, a growing body of evidence suggests a subset of individuals are exposed, but mediate rapid viral clearance before the infection is detected by PCR or seroconversion. This type of "abortive" infection likely represents a dead-end in transmission and precludes the possibility for development of disease. It is, therefore, a desirable outcome on exposure and a setting in which highly effective immunity can be studied. Here, we describe how early sampling of a new pandemic virus using sensitive immunoassays and a novel transcriptomic signature can identify abortive infections. Despite the challenges in identifying abortive infections, we highlight diverse lines of evidence supporting their occurrence. In particular, expansion of virus-specific T cells in seronegative individuals suggests abortive infections occur not only after exposure to SARS-CoV-2, but for other
    MeSH term(s) Humans ; SARS-CoV-2 ; COVID-19 ; T-Lymphocytes ; Antibodies, Viral
    Chemical Substances Antibodies, Viral
    Language English
    Publishing date 2023-02-22
    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/ijms24054371
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  2. Article ; Online: Can T Cells Abort SARS-CoV-2 and Other Viral Infections?

    Leo Swadling / Mala K. Maini

    International Journal of Molecular Sciences, Vol 24, Iss 4371, p

    2023  Volume 4371

    Abstract: Despite the highly infectious nature of the SARS-CoV-2 virus, it is clear that some individuals with potential exposure, or even experimental challenge with the virus, resist developing a detectable infection. While a proportion of seronegative ... ...

    Abstract Despite the highly infectious nature of the SARS-CoV-2 virus, it is clear that some individuals with potential exposure, or even experimental challenge with the virus, resist developing a detectable infection. While a proportion of seronegative individuals will have completely avoided exposure to the virus, a growing body of evidence suggests a subset of individuals are exposed, but mediate rapid viral clearance before the infection is detected by PCR or seroconversion. This type of “abortive” infection likely represents a dead-end in transmission and precludes the possibility for development of disease. It is, therefore, a desirable outcome on exposure and a setting in which highly effective immunity can be studied. Here, we describe how early sampling of a new pandemic virus using sensitive immunoassays and a novel transcriptomic signature can identify abortive infections. Despite the challenges in identifying abortive infections, we highlight diverse lines of evidence supporting their occurrence. In particular, expansion of virus-specific T cells in seronegative individuals suggests abortive infections occur not only after exposure to SARS-CoV-2, but for other coronaviridae , and diverse viral infections of global health importance (e.g., HIV, HCV, HBV). We discuss unanswered questions related to abortive infection, such as: ‘Are we just missing antibodies? Are T cells an epiphenomenon? What is the influence of the dose of viral inoculum?’ Finally, we argue for a refinement of the current paradigm that T cells are only involved in clearing established infection; instead, we emphasise the importance of considering their role in terminating early viral replication by studying abortive infections.
    Keywords SARS-CoV-2 ; T cell ; abortive infection ; seronegative ; adaptive immunity ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 570
    Language English
    Publishing date 2023-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: T cell control of SARS-CoV-2: When, which, and where?

    Diniz, Mariana O / Maini, Mala K / Swadling, Leo

    Seminars in immunology

    2023  Volume 70, Page(s) 101828

    Abstract: Efficient immune protection against viruses such as SARS-CoV-2 requires the coordinated activity of innate immunity, B and T cells. Accumulating data point to a critical role for T cells not only in the clearance of established infection, but also for ... ...

    Abstract Efficient immune protection against viruses such as SARS-CoV-2 requires the coordinated activity of innate immunity, B and T cells. Accumulating data point to a critical role for T cells not only in the clearance of established infection, but also for aborting viral replication independently of humoral immunity. Here we review the evidence supporting the contribution of antiviral T cells and consider which of their qualitative features favour efficient control of infection. We highlight how studies of SARS-CoV-2 and other coronaviridae in animals and humans have provided important lessons on the optimal timing (When), functionality and specificity (Which), and location (Where) of antiviral T cells. We discuss the clinical implications, particularly for the development of next-generation vaccines, and emphasise areas requiring further study.
    MeSH term(s) Animals ; Humans ; SARS-CoV-2 ; COVID-19 ; T-Lymphocytes ; Immunity, Humoral ; Antiviral Agents ; Vaccination ; Antibodies, Viral
    Chemical Substances Antiviral Agents ; Antibodies, Viral
    Language English
    Publishing date 2023-08-29
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1018141-6
    ISSN 1096-3618 ; 1044-5323
    ISSN (online) 1096-3618
    ISSN 1044-5323
    DOI 10.1016/j.smim.2023.101828
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    Zs.A 2843: Show issues Location:
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  4. Article ; Online: T cells in COVID-19 - united in diversity.

    Swadling, Leo / Maini, Mala K

    Nature immunology

    2020  Volume 21, Issue 11, Page(s) 1307–1308

    MeSH term(s) Betacoronavirus ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; COVID-19 ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; SARS Virus ; SARS-CoV-2 ; United Kingdom
    Keywords covid19
    Language English
    Publishing date 2020-09-07
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-020-0798-y
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  5. Article ; Online: The liver as an immunological barrier redefined by single-cell analysis.

    Stamataki, Zania / Swadling, Leo

    Immunology

    2020  Volume 160, Issue 2, Page(s) 157–170

    Abstract: The liver is a front-line immune tissue that plays a major role in the detection, capture and clearance of pathogens and foreign antigens entering the bloodstream, especially from the gut. Our largest internal organ maintains this immune barrier in the ... ...

    Abstract The liver is a front-line immune tissue that plays a major role in the detection, capture and clearance of pathogens and foreign antigens entering the bloodstream, especially from the gut. Our largest internal organ maintains this immune barrier in the face of constant exposure to external but harmless antigens through a highly specialized network of liver-adapted immune cells. Mapping the immune resident compartment in the liver has been challenging because it requires multimodal single-cell deep phenotyping approaches of often rare cell populations in difficult to access samples. We can now measure the RNA transcripts present in a single cell (scRNA-seq), which is revolutionizing the way we characterize cell types. scRNA-seq has been applied to the diverse array of immune cells present in murine and human livers in health and disease. Here, we summarize how emerging single-cell technologies have advanced or redefined our understanding of the immunological barrier provided by the liver.
    MeSH term(s) Animals ; Antigens/immunology ; Gene Expression Regulation/immunology ; Host-Pathogen Interactions/immunology ; Humans ; Liver/immunology ; Liver/metabolism ; Mice ; RNA-Seq ; Single-Cell Analysis ; Transcriptome/immunology
    Chemical Substances Antigens
    Language English
    Publishing date 2020-04-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80124-0
    ISSN 1365-2567 ; 0019-2805 ; 0953-4954
    ISSN (online) 1365-2567
    ISSN 0019-2805 ; 0953-4954
    DOI 10.1111/imm.13193
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  7. Article ; Online: Liver-resident CD8+ T cells: Learning lessons from the local experts.

    Swadling, Leo / Pallett, Laura J / Maini, Mala K

    Journal of hepatology

    2020  Volume 72, Issue 6, Page(s) 1049–1051

    MeSH term(s) Basic Helix-Loop-Helix Transcription Factors ; CD8-Positive T-Lymphocytes ; Humans ; Liver
    Chemical Substances Basic Helix-Loop-Helix Transcription Factors
    Language English
    Publishing date 2020-02-28
    Publishing country Netherlands
    Document type Editorial ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 605953-3
    ISSN 1600-0641 ; 0168-8278
    ISSN (online) 1600-0641
    ISSN 0168-8278
    DOI 10.1016/j.jhep.2020.02.001
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    Zs.A 2027: Show issues Location:
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  8. Article ; Online: T cells in COVID-19 — united in diversity

    Swadling, Leo / Maini, Mala K.

    Nature Immunology ; ISSN 1529-2908 1529-2916

    2020  

    Keywords Immunology ; covid19
    Language English
    Publisher Springer Science and Business Media LLC
    Publishing country us
    Document type Article ; Online
    DOI 10.1038/s41590-020-0798-y
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Airway-resident T cells from unexposed individuals cross-recognize SARS-CoV-2.

    Diniz, Mariana O / Mitsi, Elena / Swadling, Leo / Rylance, Jamie / Johnson, Marina / Goldblatt, David / Ferreira, Daniela / Maini, Mala K

    Nature immunology

    2022  Volume 23, Issue 9, Page(s) 1324–1329

    Abstract: T cells can contribute to clearance of respiratory viruses that cause acute-resolving infections such as SARS-CoV-2, helping to provide long-lived protection against disease. Recent studies have suggested an additional role for T cells in resisting overt ...

    Abstract T cells can contribute to clearance of respiratory viruses that cause acute-resolving infections such as SARS-CoV-2, helping to provide long-lived protection against disease. Recent studies have suggested an additional role for T cells in resisting overt infection: pre-existing cross-reactive responses were preferentially enriched in healthcare workers who had abortive infections
    MeSH term(s) Animals ; Antibodies, Viral ; COVID-19 ; Cross Reactions ; Humans ; Mice ; Pandemics ; Respiratory System ; SARS-CoV-2
    Chemical Substances Antibodies, Viral
    Language English
    Publishing date 2022-08-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-022-01292-1
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    Zs.A 5294: Show issues Location:
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  10. Article ; Online: The past, current and future epidemiological dynamic of SARS-CoV-2.

    Balloux, François / Tan, Cedric / Swadling, Leo / Richard, Damien / Jenner, Charlotte / Maini, Mala / van Dorp, Lucy

    Oxford open immunology

    2022  Volume 3, Issue 1, Page(s) iqac003

    Abstract: SARS-CoV-2, the agent of the COVID-19 pandemic, emerged in late 2019 in China, and rapidly spread throughout the world to reach all continents. As the virus expanded in its novel human host, viral lineages diversified through the accumulation of around ... ...

    Abstract SARS-CoV-2, the agent of the COVID-19 pandemic, emerged in late 2019 in China, and rapidly spread throughout the world to reach all continents. As the virus expanded in its novel human host, viral lineages diversified through the accumulation of around two mutations a month on average. Different viral lineages have replaced each other since the start of the pandemic, with the most successful Alpha, Delta and Omicron variants of concern (VoCs) sequentially sweeping through the world to reach high global prevalence. Neither Alpha nor Delta was characterized by strong immune escape, with their success coming mainly from their higher transmissibility. Omicron is far more prone to immune evasion and spread primarily due to its increased ability to (re-)infect hosts with prior immunity. As host immunity reaches high levels globally through vaccination and prior infection, the epidemic is expected to transition from a pandemic regime to an endemic one where seasonality and waning host immunization are anticipated to become the primary forces shaping future SARS-CoV-2 lineage dynamics. In this review, we consider a body of evidence on the origins, host tropism, epidemiology, genomic and immunogenetic evolution of SARS-CoV-2 including an assessment of other coronaviruses infecting humans. Considering what is known so far, we conclude by delineating scenarios for the future dynamic of SARS-CoV-2, ranging from the good-circulation of a fifth endemic 'common cold' coronavirus of potentially low virulence, the bad-a situation roughly comparable with seasonal flu, and the ugly-extensive diversification into serotypes with long-term high-level endemicity.
    Language English
    Publishing date 2022-06-20
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2633-6960
    ISSN (online) 2633-6960
    DOI 10.1093/oxfimm/iqac003
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