Immunogenicity and protective efficacy induced by self-amplifying mRNA vaccines encoding bacterial antigens
| Autor: | Immaculada Margarit, Giuliano Bensi, Domenico Maione, Emiliano Chiarot, Stefano Bonacci, Andrew Geall, Scilla Buccato, Giulietta Maruggi, Elisabetta Frigimelica, Cinzia Giovani |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Streptococcus pyogenes Biology Pilus Streptococcus agalactiae Viral vector Microbiology Mice 03 medical and health sciences 0302 clinical medicine Immune system Antigen Streptococcal Vaccines Immunology and Microbiology(all) Streptococcal Infections Animals RNA Messenger Antigens Bacterial General Veterinary General Immunology and Microbiology Immunogenicity Public Health Environmental and Occupational Health veterinary(all) Antibodies Bacterial Virology Vaccination Disease Models Animal 030104 developmental biology Infectious Diseases 030220 oncology & carcinogenesis Molecular Medicine Female Bacterial antigen |
| Zdroj: | Vaccine. 35:361-368 |
| ISSN: | 0264-410X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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