Immunogenicity and protective efficacy induced by self-amplifying mRNA vaccines encoding bacterial antigens
Open accessAbstract
Nucleic acid vaccines represent an attractive approach to vaccination, combining the positive attributes of both viral vectors and live-attenuated vaccines, without the inherent limitations of each technology. We have developed a novel technology, the Self-Amplifying mRNA (SAM) platform, which is based on the synthesis of self-amplifying mRNA formulated and delivered as a vaccine. SAM vaccines have been shown to stimulate robust innate and adaptive immune responses in small animals and non-human primates against a variety of viral antigens, thus representing a safe and versatile tool against viral infections. To assess whether the SAM technology could be used for a broader range of targets, we investigated the immunogenicity and efficacy of SAM vaccines expressing antigens from Group A (GAS) and Group B (GBS) Streptococci, as models of bacterial pathogens. Two prototype bacterial antigens (the double-mutated GAS Streptolysin-O (SLOdm) and the GBS pilus 2a backbone protein (BP-2a)) were successfully expressed by SAM vectors. Mice immunized with both vaccines produced significant amounts of fully functional serum antibodies. The antibody responses generated by SAM vaccines were capable of conferring consistent protection in murine models of GAS and GBS infections. Inclusion of a eukaryotic secretion signal or boosting with the recombinant protein resulted in higher specific-antibody levels and protection. Our results support the concept of using SAM vaccines as potential solution for a wide range of both viral and bacterial pathogens, due to the versatility of the manufacturing processes and the broad spectrum of elicited protective immune response.
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In several studies, maternal vaccination with mRNA-loaded LNPs protected mouse neonates from group A and group B streptococci.
“In several studies, maternal vaccination with mRNA-loaded LNPs prevented fetal Zika virus transmission in pregnant mice225,226 and protected mouse neonates from herpesvirus227 and group A and group B streptococci228.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [228]
Lipid nanoparticle-mRNA vaccines have been reported to induce immune protection against parasitical and bacterial infections.
“Apart from viral infections, lipid nanoparticle–mRNA vaccines have been reported to induce immune protection against parasitical31 and bacterial30,198 infections.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [30]
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- Authors
- Maruggi, G., Chiarot, E., Giovani, C., Buccato, S., Bonacci, S., Frigimelica, E., Margarit, I., Geall, A., Bensi, G., & Maione, D.
- Affiliations
- GlaxoSmithKline (United States) (US)
- Corresponding author
- Maruggi, Giulietta
- Maione, Domenico
- ORCID
- Venue
- Vaccine
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 35
- Issue
- 2
- Pages
- 361-368
- ISSN
- 0264-410X (ISSN-L)
- OpenAlex
- W2560416222
- Cited by
- 149
- References
- 48
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 27 · 2023: 21 · 2022: 21 · 2021: 29 · 2020: 9 · 2019: 10 · 2018: 9 · 2017: 2
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Vaccine (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Streptococcal Infections and Treatments
- Keywords
- self-amplifying mRNA vaccine, bacterial antigens, Streptococcus agalactiae, Streptococcus pyogenes, streptolysin O, antibody response, protective immunity, nucleic acid vaccines
- MeSH terms
- Animals, Antibodies, Bacterial, Antigens, Bacterial, Disease Models, Animal, Female, RNA, Messenger, Streptococcal Infections, Streptococcus agalactiae, Streptococcus pyogenes, Streptococcal Vaccines, Mice
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