title: A novel RNA-based adjuvant combines strong immunostimulatory capacities with a favorable safety profile.
abstract: Protein- and peptide-based tumor vaccines depend on strong adjuvants to induce potent immune responses. Here, we demonstrated that a recently developed novel adjuvant based on a non-coding, long-chain RNA molecule, termed RNAdjuvant(®) , profoundly increased immunogenicity of both antigen formats. RNAdjuvant(®) induced balanced, long-lasting immune responses that resulted in a strong anti-tumor activity. A direct comparison to Poly(I:C) showed superior efficacy of our adjuvant to enhance antigen-specific multifunctional CD8(+) T-cell responses and mediate anti-tumor responses induced by peptide derived from HPV-16 E7 protein in the syngeneic TC-1 tumor, a murine model of human HPV-induced cervical cancer. Moreover, the adjuvant was able to induce functional memory responses that mediated complete tumor remission. Despite its remarkable immunostimulatory activity, our RNA-based adjuvant exhibited an excellent pre-clinical safety profile. It acted only locally at the injection site where it elicited a transient but strong up-regulation of pro-inflammatory and anti-viral cytokines as well as cytoplasmic RNA sensors without systemic cytokine release. This was followed by the activation of immune cells in the draining lymph nodes. Our data indicate that our RNA-based adjuvant is a safe and potent immunostimulator that may profoundly improve the efficacy of a variety of cancer vaccines.
authors.affiliation: CureVac GmbH, Department of pre-clinical research, Paul-Ehrlich-Str. 15, Tübingen, 72076, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Heidenreich
authors.affiliation: CureVac GmbH, Department of pre-clinical research, Paul-Ehrlich-Str. 15, Tübingen, 72076, Germany.
authors.forename: Edith
authors.initials: E
authors.lastname: Jasny
authors.affiliation: CureVac GmbH, Department of pre-clinical research, Paul-Ehrlich-Str. 15, Tübingen, 72076, Germany.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Kowalczyk
authors.affiliation: CureVac GmbH, Department of pre-clinical research, Paul-Ehrlich-Str. 15, Tübingen, 72076, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Lutz
authors.affiliation: IDT Biologika GmbH, Quality Unit Vaccines, Dessau-Roßlau, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Probst
authors.affiliation: CureVac GmbH, Department of pre-clinical research, Paul-Ehrlich-Str. 15, Tübingen, 72076, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Baumhof
authors.affiliation: CureVac GmbH, Department of pre-clinical research, Paul-Ehrlich-Str. 15, Tübingen, 72076, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Scheel
authors.affiliation: CureVac GmbH, Department of pre-clinical research, Paul-Ehrlich-Str. 15, Tübingen, 72076, Germany.
authors.forename: Söhnke
authors.initials: S
authors.lastname: Voss
authors.affiliation: CureVac GmbH, Department of pre-clinical research, Paul-Ehrlich-Str. 15, Tübingen, 72076, Germany.
authors.forename: Karl-Josef
authors.initials: KJ
authors.lastname: Kallen
authors.affiliation: CureVac GmbH, Department of pre-clinical research, Paul-Ehrlich-Str. 15, Tübingen, 72076, Germany.
authors.forename: Mariola
authors.initials: M
authors.lastname: Fotin-Mleczek
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology* / Q000494:pharmacology; D002461:Cell Line, Transformed; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050725:Papillomavirus E7 Proteins / Q000276:immunology; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D062085:RNA, Long Noncoding / Q000235:genetics / Q000276:immunology*; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D016207:Cytokines; D050725:Papillomavirus E7 Proteins; D010455:Peptides; D062085:RNA, Long Noncoding; C059731:oncogene protein E7, Human papillomavirus type 16; D011070:Poly I-C
keywords: HPV-16; Key words: adjuvant; RNA; RNAdjuvant; TC-1; TLR; cancer immunotherapy; peptide vaccine; poly(I:C); protein vaccine