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Chimeric Fusion (F) and Attachment (G) Glycoprotein Antigen Delivery by mRNA as a Candidate Nipah Vaccine

  1. Author:
    Loomis, Rebecca J.
    DiPiazza, Anthony T.
    Falcone, Samantha
    Ruckwardt, Tracy J.
    Morabito, Kaitlyn M.
    Abiona, Olubukola M.
    Chang, Lauren A.
    Caringal, Ria T.
    Presnyak, Vladimir
    Narayanan, Elisabeth
    Tsybovsky,Yaroslav
    Nair, Deepika
    Hutchinson, Geoffrey B.
    Stewart-Jones, Guillaume B. E.
    Kueltzo, Lisa A.
    Himansu, Sunny
    Mascola, John R.
    Carfi, Andrea
    Graham, Barney S.

  2. Author Address

    NIAID, Natl Inst Hlth, Viral Pathogenesis Lab, Vaccine Res Ctr, Bethesda, MD 20892 USA.Moderna Inc, Cambridge, MA USA.NIAID, Natl Inst Hlth, Vaccine Res Ctr, Vaccine Prod Program, Bethesda, MD 20892 USA.Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Vaccine Res Ctr Elect Microscopy Unit, Canc Res Technol Program, Frederick, MD USA.NIAID, Natl Inst Hlth, Natl Inst Allergy & Infect Dis, Vaccine Res Ctr,Virol Lab, Bethesda, MD 20892 USA.
    1. Year: 2021
    2. Date: Dec 8
  2. Journal: Frontiers in Immunology
  3. Frontiers Media SA
    1. 12
  5. Type of Article: Article
  6. Article Number: ARTN 772864
  7. ISSN: 1664-3224
  1. Abstract:

    Nipah virus (NiV) represents a significant pandemic threat with zoonotic transmission from bats-to-humans with almost annual regional outbreaks characterized by documented human-to-human transmission and high fatality rates. Currently, no vaccine against NiV has been approved. Structure-based design and protein engineering principles were applied to stabilize the fusion (F) protein in its prefusion trimeric conformation (pre-F) to improve expression and increase immunogenicity. We covalently linked the stabilized pre-F through trimerization domains at the C-terminus to three attachment protein (G) monomers, forming a chimeric design. These studies detailed here focus on mRNA delivery of NiV immunogens in mice, assessment of mRNA immunogen-specific design elements and their effects on humoral and cellular immunogenicity. The pre-F/G chimera elicited a strong neutralizing antibody response and a superior NiV-specific Tfh and other effector T cell response compared to G alone across both the mRNA and protein platforms. These findings enabled final candidate selection of pre-F/G Fd for clinical development.

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External Sources

  1. View Full Text
  2. DOI: 10.3389/fimmu.2021.772864
  3. PMID: 34956199
  4. PMCID: PMC8692728
  5. View record in Web of Science®
  6. WOS: 000732727500001

Library Notes

  1. Fiscal Year: FY2021-2022
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