A self-amplifying RNA vaccine against COVID-19 with long-term room-temperature stability
Open accessPublished version of a preprint
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.
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The current understanding of the field is that incorporating modified NTPs into saRNA abrogates downstream efficacy.
“However, the current understanding of the field is that incorporating modified NTPs into saRNA abrogates downstream efficacy, as reported by multiple independent groups5,19–28.”
From Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency (2025) · cites this paper as [20]
The Results section (“Antigen optimization increases SARS-CoV-2 variant cross-neutralization”; page unavailable) reports that making this saRNA vaccine with modified nucleosides entirely abrogated its antibody and T-cell responses in mice. That supports the claim for this vaccine, but the paper’s brief mouse study does not establish that modified NTPs generally abrogate downstream efficacy across saRNA vaccines. (LLM, conf=0.84)
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References 78 · Cited by 89
Research works printed but not linked: 2
- [47]Walsh EE Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates N. Engl. J. Med. 2020 383 2439 2450 33053279 PMC7583697
- [60]Cele S Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization Nature 2022 602 654 656 35016196 PMC8866126
- Authors
- Voigt, E. A., Gerhardt, A., Hanson, D., Jennewein, M. F., Battisti, P., Reed, S., Singh, J., Mohamath, R., Bakken, J., Beaver, S., Press, C., Soon-Shiong, P., Paddon, C. J., Fox, C. B., & Casper, C.
- Affiliations
- Access to Advanced Health Institute (US)
- Amyris (United States) (US)
- University of Washington (US)
- Corresponding author
- Voigt, Emily A.
- ORCID
- Venue
- npj Vaccines
- Published
- 2022-11-02
- Volume
- 7
- Issue
- 1
- Pages
- 136-136
- ISSN
- 2059-0105 (ISSN-L)
- PMC
- PMC9628444
- OpenAlex
- W4307922305
- Cited by
- 89
- References
- 78
- Citations by year
- 2026: 16 · 2025: 30 · 2024: 23 · 2023: 15 · 2022: 5
- FWCI
- 8.92
- Type
- journal article
- Language
- en
- Update notices
- correction (2022-11-23)
- Open access
- gold
- doi.org
- Locations
- npj Vaccines (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Amyris, Inc., and ImmunityBio, Inc.
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Keywords
- self-amplifying RNA vaccine, COVID-19 pandemic, SARS-CoV-2, nanostructured lipid carriers, room-temperature stability, mRNA vaccines, thermal stability, humoral immunity, T cell response, homologous prime-boost, vaccine storage
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