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  1. Article ; Online: Preparing for Pandemics: RNA Vaccines at the Forefront.

    Erasmus, Jesse H / Fuller, Deborah Heydenburg

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

    2020  Volume 28, Issue 7, Page(s) 1559–1560

    MeSH term(s) Animals ; Influenza Vaccines ; Influenza, Human ; Mice ; Pandemics ; RNA ; RNA, Messenger
    Chemical Substances Influenza Vaccines ; RNA, Messenger ; RNA (63231-63-0)
    Keywords covid19
    Language English
    Publishing date 2020-06-23
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1016/j.ymthe.2020.06.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5640: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Single dose, dual antigen RNA vaccines protect against lethal Crimean-Congo haemorrhagic fever virus infection in mice.

    Leventhal, Shanna S / Meade-White, Kimberly / Shaia, Carl / Tipih, Thomas / Lewis, Mathew / Mihalakakos, Evan A / Hinkley, Troy / Khandhar, Amit P / Erasmus, Jesse H / Feldmann, Heinz / Hawman, David W

    EBioMedicine

    2024  Volume 101, Page(s) 105017

    Abstract: Background: Crimean-Congo Haemorrhagic Fever Virus is a tick-borne bunyavirus prevalent across Asia, Africa, the Middle East, and Europe. The virus causes a non-specific febrile illness which may develop into severe haemorrhagic disease. To date, there ... ...

    Abstract Background: Crimean-Congo Haemorrhagic Fever Virus is a tick-borne bunyavirus prevalent across Asia, Africa, the Middle East, and Europe. The virus causes a non-specific febrile illness which may develop into severe haemorrhagic disease. To date, there are no widely approved therapeutics. Recently, we reported an alphavirus-based replicon RNA vaccine which expresses the CCHFV nucleoprotein (repNP) or glycoprotein precursor (repGPC) and is protective against lethal disease in mice.
    Methods: Here, we evaluated engineered GPC constructs to find the minimal enhancing epitope of repGPC and test two RNA vaccine approaches to express multiple antigens in vivo to optimize protective efficacy of our repRNA.
    Findings: Vaccination with repNP and a construct expressing just the Gc antigen (repGc-FL) resulted in equivalent immunogenicity and protective efficacy compared to original repNP + repGPC vaccination. This vaccine was protective when prepared in either of two vaccine approaches, a mixed synthesis reaction producing two RNAs in a single tube and a single RNA expressing two antigens.
    Interpretation: Overall, our data illustrate two vaccine approaches to deliver two antigens in a single immunization. Both approaches induced protective immune responses against CCHFV in this model. These approaches support their continued development for this and future vaccine candidates for CCHFV and other vaccines where inclusion of multiple antigens would be optimal.
    Funding: This work was supported by the Intramural Research Program, NIAID/NIH, HDT Bio and MCDC Grant #MCDC2204-011.
    MeSH term(s) Animals ; Mice ; Hemorrhagic Fever Virus, Crimean-Congo/genetics ; mRNA Vaccines ; Hemorrhagic Fever, Crimean/prevention & control ; Vaccines ; Vaccination
    Chemical Substances mRNA Vaccines ; Vaccines
    Language English
    Publishing date 2024-02-20
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2024.105017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine.

    MacMillen, Zachary / Hatzakis, Kiara / Simpson, Adrian / Shears, Melanie J / Watson, Felicia / Erasmus, Jesse H / Khandhar, Amit P / Wilder, Brandon / Murphy, Sean C / Reed, Steven G / Davie, James W / Avril, Marion

    NPJ vaccines

    2024  Volume 9, Issue 1, Page(s) 12

    Abstract: Malaria, caused by Plasmodium parasites, remains one of the most devastating infectious diseases worldwide, despite control efforts to lower morbidity and mortality. Both advanced candidate vaccines, RTS,S and R21, are subunit (SU) vaccines that target a ...

    Abstract Malaria, caused by Plasmodium parasites, remains one of the most devastating infectious diseases worldwide, despite control efforts to lower morbidity and mortality. Both advanced candidate vaccines, RTS,S and R21, are subunit (SU) vaccines that target a single Plasmodium falciparum (Pf) pre-erythrocytic (PE) sporozoite (spz) surface protein known as circumsporozoite (CS). These vaccines induce humoral immunity but fail to elicit CD8 + T-cell responses sufficient for long-term protection. In contrast, whole-organism (WO) vaccines, such as Radiation Attenuated Sporozoites (RAS), achieved sterile protection but require a series of intravenous doses administered in multiple clinic visits. Moreover, these WO vaccines must be produced in mosquitos, a burdensome process that severely limits their availability. To reduce reliance on WO while maintaining protection via both antibodies and Trm responses, we have developed an accelerated vaccination regimen that combines two distinct agents in a prime-and-trap strategy. The priming dose is a single dose of self-replicating RNA encoding the full-length P. yoelii CS protein, delivered via an advanced cationic nanocarrier (LION
    Language English
    Publishing date 2024-01-10
    Publishing country England
    Document type Journal Article
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-023-00799-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: An RNA-Based Vaccine Platform for Use against

    Larsen, Sasha E / Erasmus, Jesse H / Reese, Valerie A / Pecor, Tiffany / Archer, Jacob / Kandahar, Amit / Hsu, Fan-Chi / Nicholes, Katrina / Reed, Steven G / Baldwin, Susan L / Coler, Rhea N

    Vaccines

    2023  Volume 11, Issue 1

    Abstract: Mycobacterium ... ...

    Abstract Mycobacterium tuberculosis
    Language English
    Publishing date 2023-01-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines11010130
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Biotechnological Applications of an Insect-Specific Alphavirus.

    Erasmus, Jesse H / Weaver, Scott C

    DNA and cell biology

    2017  

    Abstract: The coupling of viral and arthropod host diversity, with evolving methods of virus discovery, has resulted in the identification and classification of a growing number of novel insect-specific viruses (ISVs) that appear to be evolutionarily related to ... ...

    Abstract The coupling of viral and arthropod host diversity, with evolving methods of virus discovery, has resulted in the identification and classification of a growing number of novel insect-specific viruses (ISVs) that appear to be evolutionarily related to many human pathogens but have either lost or have yet to gain the ability to replicate in vertebrates. The discovery of ISVs has raised many questions as to the origin and evolution of many human pathogenic viruses and points to the role that arthropods may play in this evolutionary process. Furthermore, the use of ISVs to control the transmission of arthropod-borne viruses has been proposed and demonstrated experimentally. Previously, our laboratory reported on the discovery and characterization of Eilat virus (EILV), an insect-specific alphavirus that phylogenetically groups within the mosquito-borne clade of medically relevant alphaviruses, including eastern equine encephalitis virus (EEEV) and Venezuelan equine encephalitis virus (VEEV), as well as chikungunya virus (CHIKV). Despite its evolutionary relationship to these human pathogens, EILV is unable to replicate in vertebrate cells due to blocks at attachment/entry and RNA replication. We recently demonstrated that, using a chimeric virus approach, EILV could be utilized as a platform for vaccine and diagnostic development, serving as a proof-of-concept for other ISVs. Due to the vast abundance of ISVs, there is an untapped resource for the development of vaccines and diagnostics for a variety of human pathogens and further work in this area is warranted.
    Language English
    Publishing date 2017-11-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1024454-2
    ISSN 1557-7430 ; 0198-0238 ; 1044-5498
    ISSN (online) 1557-7430
    ISSN 0198-0238 ; 1044-5498
    DOI 10.1089/dna.2017.4019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2061: Show issues Location:
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  7. Article: Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine.

    MacMillen, Zachary / Hatzakis, Kiara / Simpson, Adrian / Shears, Melanie J / Watson, Felicia / Erasmus, Jesse H / Khandhar, Amit P / Wilder, Brandon / Murphy, Sean C / Reed, Steven G / Davie, James W / Avril, Marion

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Malaria, caused ... ...

    Abstract Malaria, caused by
    Language English
    Publishing date 2023-05-23
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.05.23.541932
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; 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  Volume 31, Issue 4, Page(s) 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 term(s) Pregnancy ; Animals ; Female ; Rabbits ; Zika Virus ; Zika Virus Infection ; Infectious Disease Transmission, Vertical/prevention & control ; Vaccines ; Antibodies, Viral ; Antibodies, Neutralizing
    Chemical Substances Vaccines ; Antibodies, Viral ; Antibodies, Neutralizing
    Language English
    Publishing date 2023-03-24
    Publishing country United States
    Document type 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5640: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  9. Article ; Online: A localizing nanocarrier formulation enables multi-target immune responses to multivalent replicating RNA with limited systemic inflammation.

    Kimura, Taishi / Leal, Joseph M / Simpson, Adrian / Warner, Nikole L / Berube, Bryan J / Archer, Jacob F / Park, Stephanie / Kurtz, Ryan / Hinkley, Troy / Nicholes, Katrina / Sharma, Shibbu / Duthie, Malcolm S / Berglund, Peter / Reed, Steven G / Khandhar, Amit P / Erasmus, Jesse H

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

    2023  Volume 31, Issue 8, Page(s) 2360–2375

    Abstract: RNA vaccines possess significant clinical promise in counteracting human diseases caused by infectious or cancerous threats. Self-amplifying replicon RNA (repRNA) has been thought to offer the potential for enhanced potency and dose sparing. However, ... ...

    Abstract RNA vaccines possess significant clinical promise in counteracting human diseases caused by infectious or cancerous threats. Self-amplifying replicon RNA (repRNA) has been thought to offer the potential for enhanced potency and dose sparing. However, repRNA is a potent trigger of innate immune responses in vivo, which can cause reduced transgene expression and dose-limiting reactogenicity, as highlighted by recent clinical trials. Here, we report that multivalent repRNA vaccination, necessitating higher doses of total RNA, could be safely achieved in mice by delivering multiple repRNAs with a localizing cationic nanocarrier formulation (LION). Intramuscular delivery of multivalent repRNA by LION resulted in localized biodistribution accompanied by significantly upregulated local innate immune responses and the induction of antigen-specific adaptive immune responses in the absence of systemic inflammatory responses. In contrast, repRNA delivered by lipid nanoparticles (LNPs) showed generalized biodistribution, a systemic inflammatory state, an increased body weight loss, and failed to induce neutralizing antibody responses in a multivalent composition. These findings suggest that in vivo delivery of repRNA by LION is a platform technology for safe and effective multivalent vaccination through mechanisms distinct from LNP-formulated repRNA vaccines.
    MeSH term(s) Humans ; Mice ; Animals ; Tissue Distribution ; RNA/genetics ; Antigens ; Immunity, Humoral ; Inflammation ; Nanoparticles
    Chemical Substances RNA (63231-63-0) ; Antigens
    Language English
    Publishing date 2023-07-03
    Publishing country United States
    Document type 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.2023.06.017
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  10. Article ; Online: Development of Vaccines for Chikungunya Fever.

    Erasmus, Jesse H / Rossi, Shannan L / Weaver, Scott C

    The Journal of infectious diseases

    2016  Volume 214, Issue suppl 5, Page(s) S488–S496

    Abstract: Chikungunya fever, an acute and often chronic arthralgic disease caused by the mosquito-borne chikungunya virus (CHIKV), has reemerged since 2004 to cause millions of cases. Because CHIKV exhibits limited antigenic diversity and is not known to be ... ...

    Abstract Chikungunya fever, an acute and often chronic arthralgic disease caused by the mosquito-borne chikungunya virus (CHIKV), has reemerged since 2004 to cause millions of cases. Because CHIKV exhibits limited antigenic diversity and is not known to be capable of reinfection, a vaccine could serve to both prevent disease and diminish human amplification during epidemic circulation. Here, we review the many promising vaccine platforms and candidates developed for CHIKV since the 1970s, including several in late preclinical or clinical development. We discuss the advantages and limitations of each, as well as the commercial and regulatory challenges to bringing a vaccine to market.
    MeSH term(s) Animals ; Antibodies, Neutralizing/blood ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; Arthralgia/prevention & control ; Arthralgia/virology ; Chikungunya Fever/immunology ; Chikungunya Fever/prevention & control ; Chikungunya Fever/virology ; Chikungunya virus/immunology ; Clinical Trials as Topic ; Epidemics/prevention & control ; Humans ; Vaccines, Attenuated/immunology ; Vaccines, Attenuated/standards ; Viral Vaccines/immunology ; Viral Vaccines/standards
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Vaccines, Attenuated ; Viral Vaccines
    Language English
    Publishing date 2016-12-15
    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/jiw271
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