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  1. Article ; Online: Interplay of infection and vaccination in long-term protection from COVID-19.

    Tan, Hyon-Xhi / Juno, Jennifer A

    The Lancet. Infectious diseases

    2022  Volume 22, Issue 6, Page(s) 744–745

    MeSH term(s) COVID-19/prevention & control ; Humans ; SARS-CoV-2 ; Vaccination
    Language English
    Publishing date 2022-04-01
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2061641-7
    ISSN 1474-4457 ; 1473-3099
    ISSN (online) 1474-4457
    ISSN 1473-3099
    DOI 10.1016/S1473-3099(22)00210-9
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  2. Article ; Online: Mucosal vaccines for SARS-CoV-2

    Devaki Pilapitiya / Adam K. Wheatley / Hyon-Xhi Tan

    EBioMedicine, Vol 92, Iss , Pp 104585- (2023)

    triumph of hope over experience

    2023  

    Abstract: Summary: Currently approved COVID-19 vaccines administered parenterally induce robust systemic humoral and cellular responses. While highly effective against severe disease, there is reduced effectiveness of these vaccines in preventing breakthrough ... ...

    Abstract Summary: Currently approved COVID-19 vaccines administered parenterally induce robust systemic humoral and cellular responses. While highly effective against severe disease, there is reduced effectiveness of these vaccines in preventing breakthrough infection and/or onward transmission, likely due to poor immunity elicited at the respiratory mucosa. As such, there has been considerable interest in developing novel mucosal vaccines that engenders more localised immune responses to provide better protection and recall responses at the site of virus entry, in contrast to traditional vaccine approaches that focus on systemic immunity. In this review, we explore the adaptive components of mucosal immunity, evaluate epidemiological studies to dissect if mucosal immunity conferred by parenteral vaccination or respiratory infection drives differential efficacy against virus acquisition or transmission, discuss mucosal vaccines undergoing clinical trials and assess key challenges and prospects for mucosal vaccine development.
    Keywords Mucosal immunity ; Vaccines ; Adaptive immunity ; Respiratory viruses ; Medicine ; R ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Mucosal vaccines for SARS-CoV-2: triumph of hope over experience.

    Pilapitiya, Devaki / Wheatley, Adam K / Tan, Hyon-Xhi

    EBioMedicine

    2023  Volume 92, Page(s) 104585

    Abstract: Currently approved COVID-19 vaccines administered parenterally induce robust systemic humoral and cellular responses. While highly effective against severe disease, there is reduced effectiveness of these vaccines in preventing breakthrough infection and/ ...

    Abstract Currently approved COVID-19 vaccines administered parenterally induce robust systemic humoral and cellular responses. While highly effective against severe disease, there is reduced effectiveness of these vaccines in preventing breakthrough infection and/or onward transmission, likely due to poor immunity elicited at the respiratory mucosa. As such, there has been considerable interest in developing novel mucosal vaccines that engenders more localised immune responses to provide better protection and recall responses at the site of virus entry, in contrast to traditional vaccine approaches that focus on systemic immunity. In this review, we explore the adaptive components of mucosal immunity, evaluate epidemiological studies to dissect if mucosal immunity conferred by parenteral vaccination or respiratory infection drives differential efficacy against virus acquisition or transmission, discuss mucosal vaccines undergoing clinical trials and assess key challenges and prospects for mucosal vaccine development.
    MeSH term(s) Humans ; COVID-19 Vaccines ; SARS-CoV-2 ; COVID-19/prevention & control ; Vaccines ; Mucous Membrane ; Vaccination ; Immunity, Mucosal ; Antibodies, Viral
    Chemical Substances COVID-19 Vaccines ; Vaccines ; Antibodies, Viral
    Language English
    Publishing date 2023-05-03
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2023.104585
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  4. Article ; Online: Nice and slow make the germinal centers go: measured and escalating antigen delivery enhance durability and quality of humoral immune responses against HIV-1.

    Tan, Hyon-Xhi / Davenport, Miles P / Kent, Stephen J / Wheatley, Adam K

    Immunology and cell biology

    2022  Volume 100, Issue 10, Page(s) 750–752

    Abstract: A recently published article has confirmed that a novel immunization method of sustained and escalating antigen delivery augments the magnitude, quality and durability of humoral immune responses. ...

    Abstract A recently published article has confirmed that a novel immunization method of sustained and escalating antigen delivery augments the magnitude, quality and durability of humoral immune responses.
    MeSH term(s) Immunity, Humoral ; HIV-1 ; Germinal Center ; Antigens ; Immunization
    Chemical Substances Antigens
    Language English
    Publishing date 2022-10-31
    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.12596
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  5. Article ; Online: Engineered Ferritin Nanoparticle Vaccines Enable Rapid Screening of Antibody Functionalization to Boost Immune Responses.

    Vu, Mai N / Pilkington, Emily H / Lee, Wen Shi / Tan, Hyon-Xhi / Davis, Thomas P / Truong, Nghia P / Kent, Stephen J / Wheatley, Adam K

    Advanced healthcare materials

    2023  Volume 12, Issue 17, Page(s) e2202595

    Abstract: Employing monoclonal antibodies to target vaccine antigens to different immune cells within lymph nodes where adaptive immunity is initiated can provide a mechanism to fine-tune the magnitude or the quality of immune responses. However, studying the ... ...

    Abstract Employing monoclonal antibodies to target vaccine antigens to different immune cells within lymph nodes where adaptive immunity is initiated can provide a mechanism to fine-tune the magnitude or the quality of immune responses. However, studying the effects of different targeting antibodies head-to-head is challenging due to the lack of a feasible method that allows rapid screening of multiple antibodies for their impact on immunogenicity. Here self-assembling ferritin nanoparticles are prepared that co-display vaccine antigens and the Fc-binding domain of Staphylococcal protein A, allowing rapid attachment of soluble antibodies to the nanoparticle surface. Using this tunable system, ten antibodies targeting different immune cell subsets are screened, with targeting to Clec9a associated with higher serum antibody titers after immunization. Immune cell targeting using ferritin nanoparticles with anti-Clec9a antibodies drives concentrated deposition of antigens within germinal centers, boosting germinal center formation and robust antibody responses. However, the capacity to augment humoral immunity is antigen-dependent, with significant boosting observed for prototypic ovalbumin immunogens but reduced effectiveness with the SARS-CoV-2 RBD. This work provides a rapid platform for screening targeting antibodies, which will accelerate mechanistic insights into optimal delivery strategies for nanoparticle-based vaccines to maximize protective immunity.
    MeSH term(s) Humans ; SARS-CoV-2 ; Ferritins ; COVID-19/prevention & control ; Vaccines ; Antigens ; Antibodies, Viral ; Immunity, Humoral ; Nanoparticles/chemistry
    Chemical Substances Ferritins (9007-73-2) ; Vaccines ; Antigens ; Antibodies, Viral
    Language English
    Publishing date 2023-02-24
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649576-4
    ISSN 2192-2659 ; 2192-2640
    ISSN (online) 2192-2659
    ISSN 2192-2640
    DOI 10.1002/adhm.202202595
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  6. Article ; Online: Poor protective potential of influenza nucleoprotein antibodies despite wide prevalence.

    Vanderven, Hillary A / Esterbauer, Robyn / Jegaskanda, Sinthujan / Tan, Hyon-Xhi / Wheatley, Adam K / Kent, Stephen J

    Immunology and cell biology

    2021  Volume 100, Issue 1, Page(s) 49–60

    Abstract: Humans are exposed to influenza virus through periodic infections. Due to these repeated exposures, human populations commonly have elevated antibody titers targeting the conserved internal influenza virus nucleoprotein (NP). Despite the presence of anti- ...

    Abstract Humans are exposed to influenza virus through periodic infections. Due to these repeated exposures, human populations commonly have elevated antibody titers targeting the conserved internal influenza virus nucleoprotein (NP). Despite the presence of anti-NP antibodies, humans are acutely susceptible to drifted influenza viruses with antigenically different surface proteins and the protective potential of human NP antibodies is unclear. In this study, high levels of anti-NP antibody and NP-specific B cells were detected in both adult humans and influenza-infected mice, confirming that NP is a major target of humoral immunity. Through sorting single B cells from influenza-exposed human adults, we generated a panel of 11 anti-NP monoclonal antibodies (mAbs). The majority of anti-NP human mAbs generated were capable of engaging cellular Fc receptors and bound NP on the surface of influenza-infected cell lines in vitro, suggesting that anti-NP mAbs have the potential to mediate downstream Fc effector functions such as antibody-dependent cellular cytotoxicity and antibody-dependent phagocytosis. However, human anti-NP mAbs were not protective in vivo when passively transferred into a murine influenza challenge model. Future in vivo studies examining the synergistic effect of anti-NP mAbs infused with other influenza-specific mAbs are warranted.
    MeSH term(s) Animals ; Antibodies, Viral ; Humans ; Influenza Vaccines ; Influenza, Human ; Mice ; Nucleoproteins ; Orthomyxoviridae Infections ; Prevalence
    Chemical Substances Antibodies, Viral ; Influenza Vaccines ; Nucleoproteins
    Language English
    Publishing date 2021-11-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 284057-1
    ISSN 1440-1711 ; 0818-9641
    ISSN (online) 1440-1711
    ISSN 0818-9641
    DOI 10.1111/imcb.12508
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  7. Article ; Online: Adenovirus vector produced Zika virus-like particles induce a long-lived neutralising antibody response in mice.

    Carrera, Julio / Aktepe, Turgut E / Earnest, Linda / Christiansen, Dale / Wheatley, Adam K / Tan, Hyon-Xhi / Chung, Amy W / Collett, Simon / McPherson, Kirsty / Torresi, Joseph / Mackenzie, Jason M / Simmons, Cameron P

    Vaccine

    2023  Volume 41, Issue 33, Page(s) 4888–4898

    Abstract: Countermeasures against Zika virus (ZIKV) epidemics are urgently needed. In this study we generated a ZIKV virus-like particle (VLP) based vaccine candidate and assessed the immunogenicity of these particles in mice. The ZIKV-VLPs were morphologically ... ...

    Abstract Countermeasures against Zika virus (ZIKV) epidemics are urgently needed. In this study we generated a ZIKV virus-like particle (VLP) based vaccine candidate and assessed the immunogenicity of these particles in mice. The ZIKV-VLPs were morphologically similar to ZIKV by electron microscopy and were recognized by anti-Flavivirus neutralising antibodies. We observed that a single dose of unadjuvanted ZIKV-VLPs, or inactivated ZIKV, generated an immune response that lasted over 6 months, but did not neutralize ZIKV infection of cells in vitro. However, when we co-administered the ZIKV VLPs with either Aluminium hydroxide (Alhydrogel®; Alum), AddaVax or Pam
    MeSH term(s) Animals ; Mice ; Zika Virus ; Antibodies, Neutralizing ; Zika Virus Infection ; Antibodies, Viral ; Viral Vaccines ; Adenoviridae
    Chemical Substances Antibodies, Neutralizing ; aluminum sulfate (34S289N54E) ; Antibodies, Viral ; Viral Vaccines
    Language English
    Publishing date 2023-06-28
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2023.06.068
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  8. Article ; Online: Improvement of immune dysregulation in individuals with long COVID at 24-months following SARS-CoV-2 infection.

    Phetsouphanh, Chansavath / Jacka, Brendan / Ballouz, Sara / Jackson, Katherine J L / Wilson, Daniel B / Manandhar, Bikash / Klemm, Vera / Tan, Hyon-Xhi / Wheatley, Adam / Aggarwal, Anupriya / Akerman, Anouschka / Milogiannakis, Vanessa / Starr, Mitchell / Cunningham, Phillip / Turville, Stuart G / Kent, Stephen J / Byrne, Anthony / Brew, Bruce J / Darley, David R /
    Dore, Gregory J / Kelleher, Anthony D / Matthews, Gail V

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 3315

    Abstract: This study investigates the humoral and cellular immune responses and health-related quality of life measures in individuals with mild to moderate long COVID (LC) compared to age and gender matched recovered COVID-19 controls (MC) over 24 months. LC ... ...

    Abstract This study investigates the humoral and cellular immune responses and health-related quality of life measures in individuals with mild to moderate long COVID (LC) compared to age and gender matched recovered COVID-19 controls (MC) over 24 months. LC participants show elevated nucleocapsid IgG levels at 3 months, and higher neutralizing capacity up to 8 months post-infection. Increased spike-specific and nucleocapsid-specific CD4
    MeSH term(s) Humans ; Post-Acute COVID-19 Syndrome ; COVID-19 ; CD8-Positive T-Lymphocytes ; Quality of Life ; SARS-CoV-2 ; Antibodies, Viral
    Chemical Substances Antibodies, Viral
    Language English
    Publishing date 2024-04-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-47720-8
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  9. Article ; Online: Monoclonal antibodies against human coronavirus NL63 spike

    Conlan, Meghan / Tan, Hyon-Xhi / Esterbauer, Robyn / Kelly, Andrew / Kent, Stephen J / Wheatley, Adam K / Lee, Wen Shi

    bioRxiv

    Abstract: The COVID-19 pandemic has illustrated the potential for monoclonal antibody therapeutics as prophylactic and therapeutic agents against pandemic viruses. No such therapeutics currently exist for other human coronaviruses. NL63 is a human alphacoronavirus ...

    Abstract The COVID-19 pandemic has illustrated the potential for monoclonal antibody therapeutics as prophylactic and therapeutic agents against pandemic viruses. No such therapeutics currently exist for other human coronaviruses. NL63 is a human alphacoronavirus that typically causes the common cold and uses the same receptor, ACE2, as the highly pathogenic SARS-CoV and SARS-CoV-2 pandemic viruses. In a cohort of healthy adults, we characterised humoral responses against the NL63 spike protein. While NL63 spike and receptor binding domain-specific binding antibodies and neutralisation activity could be detected in plasma of all subjects, memory B cells against NL63 spike were variable and relatively low in frequency compared to that against SARS-CoV-2 spike. From these donors, we isolated a panel of antibodies against NL63 spike and characterised their neutralising potential. We identified potent neutralising antibodies that recognised the receptor binding domain (RBD) and other non-RBD epitopes within spike.
    Keywords covid19
    Language English
    Publishing date 2023-03-13
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2023.03.12.532265
    Database COVID19

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  10. Article ; Online: Immune imprinting and SARS-CoV-2 vaccine design.

    Wheatley, Adam K / Fox, Annette / Tan, Hyon-Xhi / Juno, Jennifer A / Davenport, Miles P / Subbarao, Kanta / Kent, Stephen J

    Trends in immunology

    2021  Volume 42, Issue 11, Page(s) 956–959

    Abstract: Reformulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines with variant strains is being pursued to combat the global surge in infections. We hypothesize that this may be suboptimal due to immune imprinting from earlier ... ...

    Abstract Reformulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines with variant strains is being pursued to combat the global surge in infections. We hypothesize that this may be suboptimal due to immune imprinting from earlier vaccination or infection with the original SARS-CoV-2 strain. New strategies may be needed to improve efficacy of SARS-CoV-2 variant vaccines.
    MeSH term(s) COVID-19 ; COVID-19 Vaccines ; Humans ; SARS-CoV-2 ; Vaccines
    Chemical Substances COVID-19 Vaccines ; Vaccines
    Language English
    Publishing date 2021-09-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2036831-8
    ISSN 1471-4981 ; 1471-4906
    ISSN (online) 1471-4981
    ISSN 1471-4906
    DOI 10.1016/j.it.2021.09.001
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