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  1. Artikel ; Online: Evaluation of repRNA vaccine for induction and in utero transfer of maternal antibodies in a pregnant rabbit model.

    Khandhar, Amit P / Landon, Chelsea D / Archer, Jacob / Krieger, Kyle / Warner, Nikole L / Randall, Samantha / Berube, Bryan J / Erasmus, Jesse H / Sather, D Noah / Staats, Herman F

    Molecular therapy : the journal of the American Society of Gene Therapy

    2023  Band 31, Heft 4, Seite(n) 1046–1058

    Abstract: Mother-to-child transmission is a major route for infections in newborns. Vaccination in mothers to leverage the maternal immune system is a promising approach to vertically transfer protective immunity. During infectious disease outbreaks, such as the ... ...

    Abstract Mother-to-child transmission is a major route for infections in newborns. Vaccination in mothers to leverage the maternal immune system is a promising approach to vertically transfer protective immunity. During infectious disease outbreaks, such as the 2016 Zika virus (ZIKV) outbreak, rapid availability of vaccines can prove critical in reducing widespread disease burden. The recent successes of mRNA vaccines support their evaluation in pregnant animal models to justify their use in neonatal settings. Here we evaluated immunogenicity of self-amplifying replicon (repRNA) vaccines, delivered with our clinical-stage LION nanoparticle formulation, in pregnant rabbits using ZIKV and HIV-1 as model disease targets. We showed that LION/repRNA vaccines induced robust antigen-specific antibody responses in adult pregnant rabbits that passively transferred to newborn kits in utero. Using a matrixed study design, we further elucidate the effect of vaccination in kits on the presence of pre-existing maternal antibodies. Our findings showed that timing of maternal vaccination is critical in maximizing in utero antibody transfer, and subsequent vaccination in newborns maintained elevated antibody levels compared with no vaccination. Overall, our results support further development of the LION/repRNA vaccine platform for maternal and neonatal settings.
    Mesh-Begriff(e) Pregnancy ; Animals ; Female ; Rabbits ; Zika Virus ; Zika Virus Infection ; Infectious Disease Transmission, Vertical/prevention & control ; Vaccines ; Antibodies, Viral ; Antibodies, Neutralizing
    Chemische Substanzen Vaccines ; Antibodies, Viral ; Antibodies, Neutralizing
    Sprache Englisch
    Erscheinungsdatum 2023-03-24
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1016/j.ymthe.2023.02.022
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern.

    Hawman, David W / Meade-White, Kimberly / Archer, Jacob / Leventhal, Shanna S / Wilson, Drew / Shaia, Carl / Randall, Samantha / Khandhar, Amit P / Krieger, Kyle / Hsiang, Tien-Ying / Gale, Michael / Berglund, Peter / Fuller, Deborah Heydenburg / Feldmann, Heinz / Erasmus, Jesse H

    eLife

    2022  Band 11

    Abstract: Despite mass public health efforts, the SARS-CoV2 pandemic continues as of late 2021 with resurgent case numbers in many parts of the world. The emergence of SARS-CoV2 variants of concern (VoCs) and evidence that existing vaccines that were designed to ... ...

    Abstract Despite mass public health efforts, the SARS-CoV2 pandemic continues as of late 2021 with resurgent case numbers in many parts of the world. The emergence of SARS-CoV2 variants of concern (VoCs) and evidence that existing vaccines that were designed to protect from the original strains of SARS-CoV-2 may have reduced potency for protection from infection against these VoC is driving continued development of second-generation vaccines that can protect against multiple VoC. In this report, we evaluated an alphavirus-based replicating RNA vaccine expressing Spike proteins from the original SARS-CoV-2 Alpha strain and recent VoCs delivered in vivo via a lipid inorganic nanoparticle. Vaccination of both mice and Syrian Golden hamsters showed that vaccination induced potent neutralizing titers against each homologous VoC but reduced neutralization against heterologous challenges. Vaccinated hamsters challenged with homologous SARS-CoV2 variants exhibited complete protection from infection. In addition, vaccinated hamsters challenged with heterologous SARS-CoV-2 variants exhibited significantly reduced shedding of infectious virus. Our data demonstrate that this vaccine platform can be updated to target emergent VoCs, elicits significant protective immunity against SARS-CoV2 variants and supports continued development of this platform.
    Mesh-Begriff(e) Animals ; Antibodies, Neutralizing ; COVID-19/prevention & control ; COVID-19 Vaccines ; Cricetinae ; Humans ; Mice ; RNA, Viral ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus/metabolism ; Vaccines, Synthetic ; mRNA Vaccines
    Chemische Substanzen Antibodies, Neutralizing ; COVID-19 Vaccines ; RNA, Viral ; Spike Glycoprotein, Coronavirus ; Vaccines, Synthetic ; mRNA Vaccines ; spike protein, SARS-CoV-2
    Sprache Englisch
    Erscheinungsdatum 2022-02-22
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.75537
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Structure-based design of haloperidol analogues as inhibitors of acetyltransferase Eis from

    Punetha, Ankita / Green, Keith D / Garzan, Atefeh / Thamban Chandrika, Nishad / Willby, Melisa J / Pang, Allan H / Hou, Caixia / Holbrook, Selina Y L / Krieger, Kyle / Posey, James E / Parish, Tanya / Tsodikov, Oleg V / Garneau-Tsodikova, Sylvie

    RSC medicinal chemistry

    2021  Band 12, Heft 11, Seite(n) 1894–1909

    Abstract: Tuberculosis (TB), caused ... ...

    Abstract Tuberculosis (TB), caused by
    Sprache Englisch
    Erscheinungsdatum 2021-10-05
    Erscheinungsland England
    Dokumenttyp Journal Article
    ISSN 2632-8682
    ISSN (online) 2632-8682
    DOI 10.1039/d1md00239b
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Structure-Guided Optimization of Inhibitors of Acetyltransferase Eis from

    Punetha, Ankita / Ngo, Huy X / Holbrook, Selina Y L / Green, Keith D / Willby, Melisa J / Bonnett, Shilah A / Krieger, Kyle / Dennis, Emily K / Posey, James E / Parish, Tanya / Tsodikov, Oleg V / Garneau-Tsodikova, Sylvie

    ACS chemical biology

    2020  Band 15, Heft 6, Seite(n) 1581–1594

    Abstract: The enhanced intracellular survival (Eis) protein ... ...

    Abstract The enhanced intracellular survival (Eis) protein of
    Mesh-Begriff(e) Acetyltransferases/antagonists & inhibitors ; Bacterial Proteins/antagonists & inhibitors ; Drug Design ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Kanamycin Resistance/drug effects ; Microbial Sensitivity Tests ; Models, Molecular ; Molecular Structure ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/enzymology ; Structure-Activity Relationship
    Chemische Substanzen Bacterial Proteins ; Enzyme Inhibitors ; Acetyltransferases (EC 2.3.1.-)
    Sprache Englisch
    Erscheinungsdatum 2020-05-18
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1554-8937
    ISSN (online) 1554-8937
    DOI 10.1021/acschembio.0c00184
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Replicating RNA platform enables rapid response to the SARS-CoV-2 Omicron variant and elicits enhanced protection in naïve hamsters compared to ancestral vaccine.

    Hawman, David W / Meade-White, Kimberly / Clancy, Chad / Archer, Jacob / Hinkley, Troy / Leventhal, Shanna S / Rao, Deepashri / Stamper, Allie / Lewis, Matthew / Rosenke, Rebecca / Krieger, Kyle / Randall, Samantha / Khandhar, Amit P / Hao, Linhue / Hsiang, Tien-Ying / Greninger, Alexander L / Gale, Michael / Berglund, Peter / Fuller, Deborah Heydenburg /
    Rosenke, Kyle / Feldmann, Heinz / Erasmus, Jesse H

    EBioMedicine

    2022  Band 83, Seite(n) 104196

    Abstract: Background: In late 2021, the SARS-CoV-2 Omicron (B.1.1.529) variant of concern (VoC) was reported with many mutations in the viral spike protein that were predicted to enhance transmissibility and allow viral escape of neutralizing antibodies. Within ... ...

    Abstract Background: In late 2021, the SARS-CoV-2 Omicron (B.1.1.529) variant of concern (VoC) was reported with many mutations in the viral spike protein that were predicted to enhance transmissibility and allow viral escape of neutralizing antibodies. Within weeks of the first report of B.1.1.529, this VoC has rapidly spread throughout the world, replacing previously circulating strains of SARS-CoV-2 and leading to a resurgence in COVID-19 cases even in populations with high levels of vaccine- and infection-induced immunity. Studies have shown that B.1.1.529 is less sensitive to protective antibody conferred by previous infections and vaccines developed against earlier lineages of SARS-CoV-2. The ability of B.1.1.529 to spread even among vaccinated populations has led to a global public health demand for updated vaccines that can confer protection against B.1.1.529.
    Methods: We rapidly developed a replicating RNA vaccine expressing the B.1.1.529 spike and evaluated immunogenicity in mice and hamsters. We also challenged hamsters with B.1.1.529 and evaluated whether vaccination could protect against viral shedding and replication within respiratory tissue.
    Findings: We found that mice previously immunized with A.1-specific vaccines failed to elevate neutralizing antibody titers against B.1.1.529 following B.1.1.529-targeted boosting, suggesting pre-existing immunity may impact the efficacy of B.1.1.529-targeted boosters. Furthermore, we found that our B.1.1.529-targeted vaccine provides superior protection compared to the ancestral A.1-targeted vaccine in hamsters challenged with the B.1.1.529 VoC after a single dose of each vaccine.
    Interpretation: Our data suggest that B.1.1.529-targeted vaccines may provide superior protection against B.1.1.529 but pre-existing immunity and timing of boosting may need to be considered for optimum protection.
    Funding: This research was supported in part by the Intramural Research Program, NIAID/NIH, Washington Research Foundation and by grants 27220140006C (JHE), AI100625, AI151698, and AI145296 (MG).
    Mesh-Begriff(e) Animals ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19/prevention & control ; Cricetinae ; Mice ; RNA ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus/genetics ; Vaccines, Synthetic ; Viral Vaccines ; mRNA Vaccines
    Chemische Substanzen Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; Vaccines, Synthetic ; Viral Vaccines ; mRNA Vaccines ; spike protein, SARS-CoV-2 ; RNA (63231-63-0)
    Sprache Englisch
    Erscheinungsdatum 2022-08-04
    Erscheinungsland Netherlands
    Dokumenttyp Comparative Study ; Journal Article
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2022.104196
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Replicating RNA platform enables rapid response to the SARS-CoV-2 Omicron variant and elicits enhanced protection in naïve hamsters compared to ancestral vaccine

    Hawman, David W / Meade-White, Kimberly / Clancy, Chad / Archer, Jacob / Hinkley, Troy / Leventhal, Shanna / Rao, Deepashri / Stamper, Allie / Lewis, Matthew / Rosenke, Rebecca / Krieger, Kyle / Randall, Samantha / Khandhar, Amit P / Hao, Linhui / Hsiang, Tien-Ying / Greninger, Alexander L / Gale, Michael / Berglund, Peter / Fuller, Deborah Heydenburg /
    Rosenke, Kyle / Feldmann, Heinz / Erasmus, Jesse

    bioRxiv

    Abstract: In late 2021, the SARS-CoV-2 Omicron (B.1.1.529) variant of concern (VoC) was reported with many mutations in the viral spike protein that were predicted to enhance transmissibility and allow viral escape of neutralizing antibodies. Within weeks of the ... ...

    Abstract In late 2021, the SARS-CoV-2 Omicron (B.1.1.529) variant of concern (VoC) was reported with many mutations in the viral spike protein that were predicted to enhance transmissibility and allow viral escape of neutralizing antibodies. Within weeks of the first report of B.1.1.529, this VoC has rapidly spread throughout the world, replacing previously circulating strains of SARS-CoV-2 and leading to a resurgence in COVID-19 cases even in populations with high levels of vaccine- and infection-induced immunity. Initial studies have shown that B.1.1.529 is less sensitive to protective antibody conferred by previous infections and vaccines developed against earlier lineages of SARS-CoV-2. The ability of B.1.1.529 to spread even among vaccinated populations has led to a global public health demand for updated vaccines that can confer protection against B.1.1.529. We report here the rapid development of a replicating RNA vaccine expressing the B.1.1.529 spike and show that this B.1.1.529-targeted vaccine is immunogenic in mice and hamsters. Interestingly, we found that mice previously immunized with A.1-specific vaccines failed to elevate neutralizing antibody titers against B.1.1.529 following B.1.1.529-targeted boosting, suggesting pre-existing immunity may impact the efficacy of B.1.1.529- targeted boosters. Furthermore, we found that our B.1.1.529-targeted vaccine provides superior protection compared to the ancestral A.1-targeted vaccine in hamsters challenged with the B.1.1.529 VoC after a single dose of each vaccine.
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2022-02-03
    Verlag Cold Spring Harbor Laboratory
    Dokumenttyp Artikel ; Online
    DOI 10.1101/2022.01.31.478520
    Datenquelle COVID19

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