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  1. Article ; Online: Selective SARS-CoV2 BA.2 escape of antibody Fc/Fc-receptor interactions

    Yannic C. Bartsch / Deniz Cizmeci / Jaewon Kang / Hailong Gao / Wei Shi / Abishek Chandrashekar / Ai-ris Y. Collier / Bing Chen / Dan H. Barouch / Galit Alter

    iScience, Vol 26, Iss 5, Pp 106582- (2023)

    2023  

    Abstract: Summary: The number of mutations in the omicron (B.1.1.529) BA.1 variant of concern led to an unprecedented evasion of vaccine induced immunity. However, despite rise in global infections, severe disease did not increase proportionally and is likely ... ...

    Abstract Summary: The number of mutations in the omicron (B.1.1.529) BA.1 variant of concern led to an unprecedented evasion of vaccine induced immunity. However, despite rise in global infections, severe disease did not increase proportionally and is likely linked to persistent recognition of BA.1 by T cells and non-neutralizing opsonophagocytic antibodies. Yet, the emergence of new sublineage BA.2, which is more transmissible than BA.1 despite relatively preserved neutralizing antibody responses, has raised the possibility that BA.2 may evade other vaccine-induced responses. Here, we comprehensively profiled the BNT162b2 vaccine-induced response to several VOCs, including omicron BA.1 and BA.2. While vaccine-induced immune responses were compromised against both omicron sublineages, vaccine-induced antibody isotype titers, and non-neutralizing Fc effector functions were attenuated to the omicron BA.2 spike compared to BA.1. Conversely, FcγR2a and FcγR2b binding was elevated to BA.2, albeit lower than BA.1 responses, potentially contributing to persistent protection against severity of disease.
    Keywords Immunology ; Virology ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: HIV envelope antibodies and TLR7 agonist partially prevent viral rebound in chronically SHIV-infected monkeys.

    Brian Moldt / Abishek Chandrashekar / Erica N Borducchi / Joseph P Nkolola / Heather Stephenson / Mark Nagel / Magdeleine Hung / Joshua Goldsmith / Craig S Pace / Brian Carr / Nathan D Thomsen / Wade S Blair / Romas Geleziunas / Dan H Barouch

    PLoS Pathogens, Vol 18, Iss 4, p e

    2022  Volume 1010467

    Abstract: A key challenge for the development of a cure to HIV-1 infection is the persistent viral reservoir established during early infection. Previous studies using Toll-like receptor 7 (TLR7) agonists and broadly neutralizing antibodies (bNAbs) have shown ... ...

    Abstract A key challenge for the development of a cure to HIV-1 infection is the persistent viral reservoir established during early infection. Previous studies using Toll-like receptor 7 (TLR7) agonists and broadly neutralizing antibodies (bNAbs) have shown delay or prevention of viral rebound following antiretroviral therapy (ART) discontinuation in simian-human immunodeficiency virus (SHIV)-infected rhesus macaques. In these prior studies, ART was initiated early during acute infection, which limited the size and diversity of the viral reservoir. Here we evaluated in SHIV-infected rhesus macaques that did not initiate ART until 1 year into chronic infection whether the TLR7 agonist vesatolimod in combination with the bNAb PGT121, formatted either as a human IgG1, an effector enhanced IgG1, or an anti-CD3 bispecific antibody, would delay or prevent viral rebound following ART discontinuation. We found that all 3 antibody formats in combination with vesatolimod were able to prevent viral rebound following ART discontinuation in a subset of animals. These data indicate that a TLR7 agonist combined with antibodies may be a promising strategy to achieve long-term ART-free HIV remission in humans.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Impact of prior Dengue immunity on Zika vaccine protection in rhesus macaques and mice.

    Rafael A Larocca / Peter Abbink / John D Ventura / Abishek Chandrashekar / Noe Mercado / Zhenfeng Li / Erica Borducchi / Rafael A De La Barrera / Kenneth H Eckels / Kayvon Modjarrad / Michael P Busch / Nelson L Michael / Dan H Barouch

    PLoS Pathogens, Vol 17, Iss 6, p e

    2021  Volume 1009673

    Abstract: Pre-existing immunity to flaviviruses can influence the outcome of subsequent flavivirus infections. Therefore, it is critical to determine whether baseline DENV immunity may influence subsequent ZIKV infection and the protective efficacy of ZIKV ... ...

    Abstract Pre-existing immunity to flaviviruses can influence the outcome of subsequent flavivirus infections. Therefore, it is critical to determine whether baseline DENV immunity may influence subsequent ZIKV infection and the protective efficacy of ZIKV vaccines. In this study, we investigated the impact of pre-existing DENV immunity induced by vaccination on ZIKV infection and the protective efficacy of an inactivated ZIKV vaccine. Rhesus macaques and mice inoculated with a live attenuated DENV vaccine developed neutralizing antibodies (NAbs) to multiple DENV serotypes but no cross-reactive NAbs responses to ZIKV. Animals with baseline DENV NAbs did not exhibit enhanced ZIKV infection and showed no overall reduction in ZIKV vaccine protection. Moreover, passive transfer of purified DENV-specific IgG from convalescent human donors did not augment ZIKV infection in STAT2 -/- and BALB/c mice. In summary, these results suggest that baseline DENV immunity induced by vaccination does not significantly enhance ZIKV infection or impair the protective efficacy of candidate ZIKV vaccines in these models. These data can help inform immunization strategies in regions of the world with multiple circulating pathogenic flaviviruses.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques

    Victoria E. K. Walker-Sperling / Noe B. Mercado / Abishek Chandrashekar / Erica N. Borducchi / Jinyan Liu / Joseph P. Nkolola / Mark Lewis / Jeffrey P. Murry / Yunling Yang / Romas Geleziunas / Merlin L. Robb / Nelson L. Michael / Maria G. Pau / Frank Wegmann / Hanneke Schuitemaker / Emily J. Fray / Mithra R. Kumar / Janet D. Siliciano / Robert F. Siliciano /
    Dan H. Barouch

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 8

    Abstract: Antiretroviral therapy alone is insufficient in curing HIV-1 infection, due to latent viral reservoir persistency. Here, authors explore the post-virologic control of combining active and passive immunisation with vesatolimod, in a SHIV-infected rhesus ... ...

    Abstract Antiretroviral therapy alone is insufficient in curing HIV-1 infection, due to latent viral reservoir persistency. Here, authors explore the post-virologic control of combining active and passive immunisation with vesatolimod, in a SHIV-infected rhesus macaque model.
    Keywords Science ; Q
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Origin of rebound virus in chronically SIV-infected Rhesus monkeys following treatment discontinuation

    Po-Ting Liu / Brandon F. Keele / Peter Abbink / Noe B. Mercado / Jinyan Liu / Esther A. Bondzie / Abishek Chandrashekar / Erica N. Borducchi / Joseph Hesselgesser / Michael Mish / Gregory Chin / Elena Bekerman / Romas Geleziunas / Dan H. Barouch

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 9

    Abstract: The origin and nature of rebound HIV-1 virus following antiretroviral therapy (ART) discontinuation still remains unclear. Here, Liu et al. suggest that intact proviral DNA in peripheral blood and lymph node mononuclear cells during ART suppression ... ...

    Abstract The origin and nature of rebound HIV-1 virus following antiretroviral therapy (ART) discontinuation still remains unclear. Here, Liu et al. suggest that intact proviral DNA in peripheral blood and lymph node mononuclear cells during ART suppression likely is the source of viral rebound following ART discontinuation.
    Keywords Science ; Q
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Origin of rebound virus in chronically SIV-infected Rhesus monkeys following treatment discontinuation

    Po-Ting Liu / Brandon F. Keele / Peter Abbink / Noe B. Mercado / Jinyan Liu / Esther A. Bondzie / Abishek Chandrashekar / Erica N. Borducchi / Joseph Hesselgesser / Michael Mish / Gregory Chin / Elena Bekerman / Romas Geleziunas / Dan H. Barouch

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 9

    Abstract: The origin and nature of rebound HIV-1 virus following antiretroviral therapy (ART) discontinuation still remains unclear. Here, Liu et al. suggest that intact proviral DNA in peripheral blood and lymph node mononuclear cells during ART suppression ... ...

    Abstract The origin and nature of rebound HIV-1 virus following antiretroviral therapy (ART) discontinuation still remains unclear. Here, Liu et al. suggest that intact proviral DNA in peripheral blood and lymph node mononuclear cells during ART suppression likely is the source of viral rebound following ART discontinuation.
    Keywords Science ; Q
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Persistence of viral RNA in lymph nodes in ART-suppressed SIV/SHIV-infected Rhesus Macaques

    Anthony M. Cadena / John D. Ventura / Peter Abbink / Erica N. Borducchi / Hubert Tuyishime / Noe B. Mercado / Victoria Walker-Sperling / Mazuba Siamatu / Po-Ting Liu / Abishek Chandrashekar / Joseph P. Nkolola / Katherine McMahan / Nicole Kordana / Venous Hamza / Esther A. Bondzie / Emily Fray / Mithra Kumar / Stephanie Fischinger / Sally A. Shin /
    Mark G. Lewis / Robert F. Siliciano / Galit Alter / Dan H. Barouch

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 11

    Abstract: The existence of HIV reservoir and ongoing replication despite antiretroviral therapy (ART) represents a barrier for cure efforts. Here, using SIV/SHIV-infected rhesus macaque suppressed with ART for one year, the authors characterize multiple lymphoid ... ...

    Abstract The existence of HIV reservoir and ongoing replication despite antiretroviral therapy (ART) represents a barrier for cure efforts. Here, using SIV/SHIV-infected rhesus macaque suppressed with ART for one year, the authors characterize multiple lymphoid and non-lymphoid tissues and show that while the viral reservoir exhibits a wide anatomic heterogeneity, persistent viral transcription is mainly restricted to secondary lymphoid organs.
    Keywords Science ; Q
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: SARS-CoV-2 binding and neutralizing antibody levels after Ad26.COV2.S vaccination predict durable protection in rhesus macaques

    Ramon Roozendaal / Laura Solforosi / Daniel J. Stieh / Jan Serroyen / Roel Straetemans / Anna Dari / Muriel Boulton / Frank Wegmann / Sietske K. Rosendahl Huber / Joan E. M. van der Lubbe / Jenny Hendriks / Mathieu Le Gars / Liesbeth Dekking / Dominika N. Czapska-Casey / Nuria Guimera / Sarah Janssen / Sarah Tete / Abishek Chandrashekar / Noe B. Mercado /
    Jingyou Yu / Wouter Koudstaal / Juan J. Perez-Ruixo / Jerry Sadoff / Dan H. Barouch / Hanneke Schuitemaker / Roland Zahn

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 10

    Abstract: Several COVID-19 vaccines have received emergency approval, but durability of protection is unclear. Here, the authors describe correlates of protection (CoP) for the Ad26.COV2.S vaccine in rhesus macaques and report that CoP predict the protection ... ...

    Abstract Several COVID-19 vaccines have received emergency approval, but durability of protection is unclear. Here, the authors describe correlates of protection (CoP) for the Ad26.COV2.S vaccine in rhesus macaques and report that CoP predict the protection observed 6 months post vaccination.
    Keywords Science ; Q
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article: Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys

    Aid, Malika / Abishek Chandrashekar / Alan S. Perelson / Amanda J. Martinot / Amanda L. Brinkman / Dan H. Barouch / David Jetton / Edward T. Moseley / Erica N. Borducchi / Eryn Blass / Jinyan Liu / Katharine Best / Katherine Molloy / Lawrence J. Tartaglia / Mark G. Lewis / Michael Boyd / Ovini Nanayakkara / Peter Abbink / Rafael A. De La Barrera /
    Rafael A. Larocca / Ramya Nityanandam

    Cell. 2017 May 04, v. 169

    2017  

    Abstract: Zika virus (ZIKV) is associated with severe neuropathology in neonates as well as Guillain-Barré syndrome and other neurologic disorders in adults. Prolonged viral shedding has been reported in semen, suggesting the presence of anatomic viral reservoirs. ...

    Abstract Zika virus (ZIKV) is associated with severe neuropathology in neonates as well as Guillain-Barré syndrome and other neurologic disorders in adults. Prolonged viral shedding has been reported in semen, suggesting the presence of anatomic viral reservoirs. Here we show that ZIKV can persist in cerebrospinal fluid (CSF) and lymph nodes (LN) of infected rhesus monkeys for weeks after virus has been cleared from peripheral blood, urine, and mucosal secretions. ZIKV-specific neutralizing antibodies correlated with rapid clearance of virus in peripheral blood but remained undetectable in CSF for the duration of the study. Viral persistence in both CSF and LN correlated with upregulation of mechanistic target of rapamycin (mTOR), proinflammatory, and anti-apoptotic signaling pathways, as well as downregulation of extracellular matrix signaling pathways. These data raise the possibility that persistent or occult neurologic and lymphoid disease may occur following clearance of peripheral virus in ZIKV-infected individuals.
    Keywords adults ; blood ; central nervous system ; cerebrospinal fluid ; extracellular matrix ; lymph nodes ; Macaca mulatta ; neonates ; neuropathology ; neutralizing antibodies ; rapamycin ; semen ; signal transduction ; urine ; viral shedding ; viruses ; Zika virus
    Language English
    Dates of publication 2017-0504
    Size p. 610-620.e14.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2017.04.008
    Database NAL-Catalogue (AGRICOLA)

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  10. Article: Development of novel replication-defective lymphocytic choriomeningitis virus vectors expressing SIV antigens

    Penaloza MacMaster, Pablo / Abishek Chandrashekar / Anders E. Lilja / Andreas Aspoeck / Bastien Mangeat / Christine A. Bricault / Crystal Cabral / Dan H. Barouch / Daniel D. Pinschewer / Gerhard Fuhrmann / Jade Mondesir / Jennifer L. Shields / Jessica Jimenez / Joseph M. Cabral / Klaus Orlinger / M. Justin Iampietro / Matthew Lim / Michael Seaman / Nicholas M. Provine /
    Quazim A. Alayo / Thomas Monath

    Vaccine. 2017 Jan. 03, v. 35, no. 1

    2017  

    Abstract: An important focus in vaccine research is the design of vaccine vectors with low seroprevalence and high immunogenicity. Replication-incompetent lymphocytic choriomeningitis virus (rLCMV) vectors do not elicit vector-neutralizing antibody responses, and ... ...

    Abstract An important focus in vaccine research is the design of vaccine vectors with low seroprevalence and high immunogenicity. Replication-incompetent lymphocytic choriomeningitis virus (rLCMV) vectors do not elicit vector-neutralizing antibody responses, and homologous prime-boost regimens with rLCMV vectors induce boostable and protective T cell responses to model antigens in mice. However, cellular and humoral immune responses following homologous rLCMV vaccine regimens have not been rigorously evaluated in non-human primates (NHPs). To test whether rLCMV vectors constitute an effective vaccine platform in NHPs, we developed rLCMV vectors expressing SIVmac239 Env and Gag antigens and assessed their immunogenicity in mice and cynomolgus macaques. Immunization with rLCMV vaccine vectors expressing SIV Env and Gag was effective at generating SIV-specific T cell and antibody responses in both mice and NHPs. Epitope mapping using SIV Env in C57BL/6 mice demonstrated that rLCMV vectors induced sustained poly-functional responses to both dominant and subdominant epitopes. Our results suggest the potential of rLCMV vectors as vaccine candidates. Future SIV challenge experiments in rhesus macaques will be needed to assess immune protection by these vaccine vectors.
    Keywords antibodies ; epitope mapping ; epitopes ; humoral immunity ; immune response ; immunization ; Lymphocytic choriomeningitis virus ; Macaca fascicularis ; Macaca mulatta ; mice ; seroprevalence ; T-lymphocytes ; vaccine development ; vaccines
    Language English
    Dates of publication 2017-0103
    Size p. 1-9.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2016.11.063
    Database NAL-Catalogue (AGRICOLA)

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