Rise of the RNA machines – self-amplification in mRNA vaccine design
Open accessAbstract
mRNA vaccines have won the race for early COVID-19 vaccine approval, yet improvements are necessary to retain this leading role in combating infectious diseases. A next generation of self-amplifying mRNAs, also known as replicons, form an ideal vaccine platform. Replicons induce potent humoral and cellular responses with few adverse effects upon a minimal, single-dose immunization. Delivery of replicons is achieved with virus-like replicon particles (VRPs), or in nonviral vehicles such as liposomes or lipid nanoparticles. Here, we discuss innovative advances, including multivalent, mucosal, and therapeutic replicon vaccines, and highlight novelties in replicon design. As soon as essential safety evaluations have been resolved, this promising vaccine concept can transform into a widely applied clinical platform technology taking center stage in pandemic preparedness.
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GEMCOVAC-OM is a self-amplifying mRNA (samRNA) vaccine.
“First, GEMCOVAC-OM is a self-amplifying mRNA (samRNA) vaccine, which can lower the dose for administration6.”
From An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial (2024) · cites this paper as [6]
The mRNA vaccine landscape section says self-amplifying RNA vaccines can induce protection at a markedly lower initial dose than conventional mRNA vaccines. The Safety considerations section describes an approved human replicon vaccine in India, but our copy does not name GEMCOVAC-OM or establish that it is a self-amplifying mRNA vaccine (searched: GEMCOVAC-OM, GEMCOVAC). (LLM, conf=0.82)
Experimental — accuracy not yet measuredSelf-amplifying mRNA vaccines can lower the dose for administration.
“First, GEMCOVAC-OM is a self-amplifying mRNA (samRNA) vaccine, which can lower the dose for administration6.”
From An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial (2024) · cites this paper as [6]
samRNA vaccines can induce potent immune responses at lower doses due to their ability to amplify antigen production within the body, potentially reducing the risk of adverse reactions.
“samRNA vaccines can induce potent immune responses at lower doses due to their ability to amplify antigen production within the body, potentially reducing the risk of adverse reactions6,44.”
From An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial (2024) · cites this paper as [6]
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Comparative Function Analysis of Self‐Amplifying mRNA and Self‐Amplifying DNA
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Vaccination against H5 HP influenza virus leads to persistent immune response in wild king penguinsPreprint
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- Authors
- Comes, J. D. G., Pijlman, G. P., & Hick, T. A. H.
- Affiliations
- Wageningen University & Research (NL)
- Corresponding author
- Pijlman, Gorben P.
- Venue
- Trends in Biotechnology
- Publisher
- Elsevier BV
- Published
- 2023-11
- Volume
- 41
- Issue
- 11
- Pages
- 1417-1429
- ISSN
- 0167-7799 (ISSN-L)
- PMC
- PMC10266560
- OpenAlex
- W4380996827
- Cited by
- 87
- References
- 108
- Citations by year
- 2026: 22 · 2025: 33 · 2024: 26 · 2023: 5 · 2013: 1
- FWCI
- 2.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Trends in biotechnology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Socio-Environmental Systems Modeling (submittedVersion, cc-by)
- Funders
- Technology Foundation STW
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- self-amplifying mRNA, replicons, mRNA vaccines, lipid nanoparticles, liposomes, multivalent vaccine, mucosal vaccines, therapeutic vaccines, vaccine design, COVID-19 vaccines, single-dose vaccination, humoral and cellular immune response, vaccine safety
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, mRNA Vaccines, Humans, Replicon, RNA, Messenger, Vaccines, Synthetic
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