title: Immunogenicity and protective efficacy induced by self-amplifying mRNA vaccines encoding bacterial antigens.
abstract: 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.
authors.affiliation: GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy. Electronic address: giulietta.x.maruggi@gsk.com.
authors.forename: Giulietta
authors.initials: G
authors.lastname: Maruggi
authors.affiliation: GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Chiarot
authors.affiliation: GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Giovani
authors.affiliation: GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Scilla
authors.initials: S
authors.lastname: Buccato
authors.affiliation: GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonacci
authors.affiliation: GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Frigimelica
authors.affiliation: GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Immaculada
authors.initials: I
authors.lastname: Margarit
authors.affiliation: GSK Vaccines, 350 Massachusetts Avenue, Mail Stop 45SS, Cambridge, MA 02139, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Geall
authors.affiliation: GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Bensi
authors.affiliation: GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy. Electronic address: domenico.x.maione@gsk.com.
authors.forename: Domenico
authors.initials: D
authors.lastname: Maione
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D013290:Streptococcal Infections / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013292:Streptococcus agalactiae / Q000235:genetics / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000235:genetics / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D012333:RNA, Messenger; D022541:Streptococcal Vaccines
keywords: GAS; Protective immunity; SAM GBS; Self-amplifying mRNA; Vaccine