A self-amplifying RNA vaccine against COVID-19 with long-term room-temperature stability

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Abstract

mRNA vaccines were the first to be authorized for use against SARS-CoV-2 and have since demonstrated high efficacy against serious illness and death. However, limitations in these vaccines have been recognized due to their requirement for cold storage, short durability of protection, and lack of access in low-resource regions. We have developed an easily-manufactured, potent self-amplifying RNA (saRNA) vaccine against SARS-CoV-2 that is stable at room temperature. This saRNA vaccine is formulated with a nanostructured lipid carrier (NLC), providing stability, ease of manufacturing, and protection against degradation. In preclinical studies, this saRNA/NLC vaccine induced strong humoral immunity, as demonstrated by high pseudovirus neutralization titers to the Alpha, Beta, and Delta variants of concern and induction of bone marrow-resident antibody-secreting cells. Robust Th1-biased T-cell responses were also observed after prime or homologous prime-boost in mice. Notably, the saRNA/NLC platform demonstrated thermostability when stored lyophilized at room temperature for at least 6 months and at refrigerated temperatures for at least 10 months. Taken together, this saRNA delivered by NLC represents a potential improvement in RNA technology that could allow wider access to RNA vaccines for the current COVID-19 and future pandemics.

Article activity feed

  1. Cristian Smerdou

    Review 4: "A self-amplifying RNA vaccine against COVID-19 with long-term room-temperature stability"

    This preprint provides a proof-of-concept demonstration for a new COVID-19 vaccine that can be stored at room temperature. Reviewers noted that though the evidence generally justifies the main claim, more work is needed to use this as an alternative to existing licensed vaccines.

  2. Rushit N. Lodaya, Derek T. O'Hagan

    Review 3: "A self-amplifying RNA vaccine against COVID-19 with long-term room-temperature stability"

    This preprint provides a proof-of-concept demonstration for a new COVID-19 vaccine that can be stored at room temperature. Reviewers noted that though the evidence generally justifies the main claim, more work is needed to use this as an alternative to existing licensed vaccines.

  3. Hamid Mahmoudzadeh Niknam, Nastaran Sadat Savar

    Review 2: "A self-amplifying RNA vaccine against COVID-19 with long-term room-temperature stability"

    This preprint provides a proof-of-concept demonstration for a new COVID-19 vaccine that can be stored at room temperature. Reviewers noted that though the evidence generally justifies the main claim, more work is needed to use this as an alternative to existing licensed vaccines.

  4. Thomas Demoulins

    Review 1: "A self-amplifying RNA vaccine against COVID-19 with long-term room-temperature stability"

    This preprint provides a proof-of-concept demonstration for a new COVID-19 vaccine that can be stored at room temperature. Reviewers noted that though the evidence generally justifies the main claim, more work is needed to use this as an alternative to existing licensed vaccines.

  5. Strength of evidence

    Reviewers: Thomas Demoulins (University of Bern) | ๐Ÿ“˜๐Ÿ“˜๐Ÿ“˜๐Ÿ“˜๐Ÿ“˜
    Hamid Niknam, Nastaran Savar (Pasteur Institute of Iran) | ๐Ÿ“’๐Ÿ“’๐Ÿ“’โ—ป๏ธโ—ป๏ธ
    Rushit N. Lodaya, Derek T. O'Hagan (Rockville Center for Vaccines) | ๐Ÿ“’๐Ÿ“’๐Ÿ“’โ—ป๏ธโ—ป๏ธ
    Cristian Smerdou (Cima Universidad de Navarra) | ๐Ÿ“˜๐Ÿ“˜๐Ÿ“˜๐Ÿ“˜๐Ÿ“˜

  6. SciScore for 10.1101/2022.03.22.485230: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIACUC: Mouse studies: All animal work was done under the oversight of the Bloodworks Northwest Research Instituteโ€™s Institutional Animal Care and Use Committee (Seattle, WA).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serum IgG, IgG1, and IgG2a titers by ELISA: SARS CoV-2 spike protein-binding IgG antibodies in mouse serum were measured by ELISA.
    IgG1
    suggested: None
    IgG
    suggested: None
    Plates were then washed, and spike protein-bound antibodies were detected using an Anti-Mouse IgG (Fc Specific)-Alkaline Phosphatase antibody (Sigma-Aldrich, โ€ฆ