IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50774-3.html
   My bibliography  Save this article

Comparison of uridine and N1-methylpseudouridine mRNA platforms in development of an Andes virus vaccine

Author

Listed:
  • Ivan V. Kuzmin

    (University of Texas Medical Branch
    Galveston National Laboratory)

  • Ruben Soto Acosta

    (University of Texas Medical Branch
    Galveston National Laboratory)

  • Layne Pruitt

    (University of Texas Medical Branch)

  • Perry T. Wasdin

    (Vanderbilt Vaccine Center)

  • Kritika Kedarinath

    (University of Texas Medical Branch
    Galveston National Laboratory)

  • Keziah R. Hernandez

    (University of Texas Medical Branch
    Galveston National Laboratory)

  • Kristyn A. Gonzales

    (University of Texas Medical Branch)

  • Kharighan Hill

    (University of Texas Medical Branch)

  • Nicole G. Weidner

    (University of Texas Medical Branch)

  • Chad Mire

    (University of Texas Medical Branch
    Galveston National Laboratory)

  • Taylor B. Engdahl

    (Vanderbilt Vaccine Center)

  • Woohyun J. Moon

    (Acuitas Therapeutics)

  • Vsevolod Popov

    (University of Texas Medical Branch)

  • James E. Crowe

    (Vanderbilt Vaccine Center)

  • Ivelin S. Georgiev

    (Vanderbilt Vaccine Center)

  • Mariano A. Garcia-Blanco

    (University of Texas Medical Branch
    University of Virginia)

  • Robert K. Abbott

    (University of Texas Medical Branch)

  • Alexander Bukreyev

    (University of Texas Medical Branch
    Galveston National Laboratory
    University of Texas Medical Branch)

Abstract

The rodent-borne Andes virus (ANDV) causes a severe disease in humans. We developed an ANDV mRNA vaccine based on the M segment of the viral genome, either with regular uridine (U-mRNA) or N1-methylpseudouridine (m1Ψ-mRNA). Female mice immunized by m1Ψ-mRNA developed slightly greater germinal center (GC) responses than U-mRNA-immunized mice. Single cell RNA and BCR sequencing of the GC B cells revealed similar levels of activation, except an additional cluster of cells exhibiting interferon response in animals vaccinated with U-mRNA but not m1Ψ-mRNA. Similar immunoglobulin class-switching and somatic hypermutations were observed in response to the vaccines. Female Syrian hamsters were immunized via a prime–boost regimen with two doses of each vaccine. The titers of glycoprotein-binding antibodies were greater for U-mRNA construct than for m1Ψ-mRNA construct; however, the titers of ANDV-neutralizing antibodies were similar. Vaccinated animals were challenged with a lethal dose of ANDV, along with a naïve control group. All control animals and two animals vaccinated with a lower dose of m1Ψ-mRNA succumbed to infection whereas other vaccinated animals survived without evidence of virus replication. The data demonstrate the development of a protective vaccine against ANDV and the lack of a substantial effect of m1Ψ modification on immunogenicity and protection in rodents.

Suggested Citation

  • Ivan V. Kuzmin & Ruben Soto Acosta & Layne Pruitt & Perry T. Wasdin & Kritika Kedarinath & Keziah R. Hernandez & Kristyn A. Gonzales & Kharighan Hill & Nicole G. Weidner & Chad Mire & Taylor B. Engdah, 2024. "Comparison of uridine and N1-methylpseudouridine mRNA platforms in development of an Andes virus vaccine," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50774-3
    DOI: 10.1038/s41467-024-50774-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50774-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-50774-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Jeong Hyun Lee & Henry J. Sutton & Christopher A. Cottrell & Ivy Phung & Gabriel Ozorowski & Leigh M. Sewall & Rebecca Nedellec & Catherine Nakao & Murillo Silva & Sara T. Richey & Jonathan L. Torres , 2022. "Long-primed germinal centres with enduring affinity maturation and clonal migration," Nature, Nature, vol. 609(7929), pages 998-1004, September.
    2. M. Büttner & J. Ostner & C. L. Müller & F. J. Theis & B. Schubert, 2021. "scCODA is a Bayesian model for compositional single-cell data analysis," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    3. Thomas E. Mulroney & Tuija Pöyry & Juan Carlos Yam-Puc & Maria Rust & Robert F. Harvey & Lajos Kalmar & Emily Horner & Lucy Booth & Alexander P. Ferreira & Mark Stoneley & Ritwick Sawarkar & Alexander, 2024. "N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting," Nature, Nature, vol. 625(7993), pages 189-194, January.
    4. Elie Dolgin, 2021. "CureVac COVID vaccine let-down spotlights mRNA design challenges," Nature, Nature, vol. 594(7864), pages 483-483, June.
    5. Ariën Schiepers & Marije F. L. Wout & Allison J. Greaney & Trinity Zang & Hiromi Muramatsu & Paulo J. C. Lin & Ying K. Tam & Luka Mesin & Tyler N. Starr & Paul D. Bieniasz & Norbert Pardi & Jesse D. B, 2023. "Molecular fate-mapping of serum antibody responses to repeat immunization," Nature, Nature, vol. 615(7952), pages 482-489, March.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Jonas Engesser & Robin Khatri & Darius P. Schaub & Yu Zhao & Hans-Joachim Paust & Zeba Sultana & Nariaki Asada & Jan-Hendrik Riedel & Varshi Sivayoganathan & Anett Peters & Anna Kaffke & Saskia-Lariss, 2024. "Immune profiling-based targeting of pathogenic T cells with ustekinumab in ANCA-associated glomerulonephritis," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Yi Huang & Anyongqi Wang & Wenjiang Zhou & Baoguo Li & Linshan Zhang & Agata M. Rudolf & Zengguang Jin & Catherine Hambly & Guanlin Wang & John R. Speakman, 2024. "Maternal dietary fat during lactation shapes single nucleus transcriptomic profile of postnatal offspring hypothalamus in a sexually dimorphic manner in mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Davide Pisu & Luana Johnston & Joshua T. Mattila & David G. Russell, 2024. "The frequency of CD38+ alveolar macrophages correlates with early control of M. tuberculosis in the murine lung," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Kaya J. E. Matson & Daniel E. Russ & Claudia Kathe & Isabelle Hua & Dragan Maric & Yi Ding & Jonathan Krynitsky & Randall Pursley & Anupama Sathyamurthy & Jordan W. Squair & Boaz P. Levi & Gregoire Co, 2022. "Single cell atlas of spinal cord injury in mice reveals a pro-regenerative signature in spinocerebellar neurons," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Ivy Phung & Kristen A. Rodrigues & Ester Marina-Zárate & Laura Maiorino & Bapi Pahar & Wen-Hsin Lee & Mariane Melo & Amitinder Kaur & Carolina Allers & Marissa Fahlberg & Brooke F. Grasperge & Jason P, 2023. "A combined adjuvant approach primes robust germinal center responses and humoral immunity in non-human primates," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Sebastian Schmidt & Malte D. Luecken & Dietrich Trümbach & Sina Hembach & Kristina M. Niedermeier & Nicole Wenck & Klaus Pflügler & Constantin Stautner & Anika Böttcher & Heiko Lickert & Ciro Ramirez-, 2022. "Primary cilia and SHH signaling impairments in human and mouse models of Parkinson’s disease," Nature Communications, Nature, vol. 13(1), pages 1-25, December.
    7. Alexander C. Dowell & Tara Lancaster & Rachel Bruton & Georgina Ireland & Christopher Bentley & Panagiota Sylla & Jianmin Zuo & Sam Scott & Azar Jadir & Jusnara Begum & Thomas Roberts & Christine Step, 2023. "Immunological imprinting of humoral immunity to SARS-CoV-2 in children," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    8. Andrew Gibson & Ramesh Ram & Rama Gangula & Yueran Li & Eric Mukherjee & Amy M. Palubinsky & Chelsea N. Campbell & Michael Thorne & Katherine C. Konvinse & Phuti Choshi & Pooja Deshpande & Sarah Pedre, 2024. "Multiomic single-cell sequencing defines tissue-specific responses in Stevens-Johnson syndrome and toxic epidermal necrolysis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    9. Annemart Koornneef & Kanika Vanshylla & Gijs Hardenberg & Lucy Rutten & Nika M. Strokappe & Jeroen Tolboom & Jessica Vreugdenhil & Karin Feddes-de Boer & Aditya Perkasa & Sven Blokland & Judith A. Bur, 2024. "CoPoP liposomes displaying stabilized clade C HIV-1 Env elicit tier 2 multiclade neutralization in rabbits," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    10. Drew R. Neavin & Angela M. Steinmann & Nona Farbehi & Han Sheng Chiu & Maciej S. Daniszewski & Himanshi Arora & Yasmin Bermudez & Cátia Moutinho & Chia-Ling Chan & Monique Bax & Mubarika Tyebally & Vi, 2023. "A village in a dish model system for population-scale hiPSC studies," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    11. Alok K. Maity & Andrew E. Teschendorff, 2023. "Cell-attribute aware community detection improves differential abundance testing from single-cell RNA-Seq data," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    12. Seongryong Kim & Ji Hyang Jeon & Myeonghwan Kim & Yeji Lee & Yun-Ho Hwang & Myungsun Park & C. Han Li & Taeyoung Lee & Jung-Ah Lee & You-Me Kim & Dokeun Kim & Hyukjin Lee & You-Jin Kim & V. Narry Kim , 2024. "Innate immune responses against mRNA vaccine promote cellular immunity through IFN-β at the injection site," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    13. Luca M. Zaeck & Ngoc H. Tan & Wim J. R. Rietdijk & Daryl Geers & Roos S. G. Sablerolles & Susanne Bogers & Laura L. A. Dijk & Lennert Gommers & Leanne P. M. Leeuwen & Sharona Rugebregt & Abraham Goorh, 2024. "Original COVID-19 priming regimen impacts the immunogenicity of bivalent BA.1 and BA.5 boosters," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    14. Praveen Weeratunga & Laura Denney & Joshua A. Bull & Emmanouela Repapi & Martin Sergeant & Rachel Etherington & Chaitanya Vuppussetty & Gareth D. H. Turner & Colin Clelland & Jeongmin Woo & Amy Cross , 2023. "Single cell spatial analysis reveals inflammatory foci of immature neutrophil and CD8 T cells in COVID-19 lungs," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    15. Sara G. Danielli & Yun Wei & Michael A. Dyer & Elizabeth Stewart & Heather Sheppard & Marco Wachtel & Beat W. Schäfer & Anand G. Patel & David M. Langenau, 2024. "Single cell transcriptomic profiling identifies tumor-acquired and therapy-resistant cell states in pediatric rhabdomyosarcoma," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    16. Larance Ronsard & Ashraf S. Yousif & Faez Amokrane Nait Mohamed & Jared Feldman & Vintus Okonkwo & Caitlin McCarthy & Julia Schnabel & Timothy Caradonna & Ralston M. Barnes & Daniel Rohrer & Nils Lonb, 2023. "Engaging an HIV vaccine target through the acquisition of low B cell affinity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    17. Marta Ferreira-Gomes & Yidan Chen & Pawel Durek & Hector Rincon-Arevalo & Frederik Heinrich & Laura Bauer & Franziska Szelinski & Gabriela Maria Guerra & Ana-Luisa Stefanski & Antonia Niedobitek & Ann, 2024. "Recruitment of plasma cells from IL-21-dependent and IL-21-independent immune reactions to the bone marrow," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    18. Eike-Christian Wamhoff & Larance Ronsard & Jared Feldman & Grant A. Knappe & Blake M. Hauser & Anna Romanov & James Brett Case & Shilpa Sanapala & Evan C. Lam & Kerri J. St. Denis & Julie Boucau & Amy, 2024. "Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    19. Michael T. H. Ng & Rowie Borst & Hamez Gacaferi & Sarah Davidson & Jessica E. Ackerman & Peter A. Johnson & Caio C. Machado & Ian Reekie & Moustafa Attar & Dylan Windell & Mariola Kurowska-Stolarska &, 2024. "A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    20. Rachael M. Zemek & Wee Loong Chin & Vanessa S. Fear & Ben Wylie & Thomas H. Casey & Cath Forbes & Caitlin M. Tilsed & Louis Boon & Belinda B. Guo & Anthony Bosco & Alistair R. R. Forrest & Michael J. , 2022. "Temporally restricted activation of IFNβ signaling underlies response to immune checkpoint therapy in mice," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50774-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.