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 V R , profoundly increased immunogenicity of both antigen formats. RNAdjuvant V R 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 CD81 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.

Current state in the development of candidate therapeutic HPV vaccines

“…A novel adjuvant consisting of a synthetic RNA cross-linked with polymeric carrier has been shown to be capable of activating murine TLR-7 or human TLR-8 pathway [82]. TC-1 tumor bearing mice vaccinated with HPV-16 E7 peptide and RNA adjuvant generated a greater E7-specific CD8+ CTL responses and antitumor effects compared to mice vaccinated with E7 peptide only or E7 peptide with immune stimulant polyinosinic:polycytidylic acid (Poly I:C).…”

Induction of Broad-Based Immunity and Protective Efficacy by Self-amplifying mRNA Vaccines Encoding Influenza Virus Hemagglutinin

“…Furthermore, in the process of amplification of their genomes, RNA replicons engage pattern recognition receptors in the host cell, adjuvanting the responses to the encoded immunogen (45)(46)(47). Although both mRNA-and replicon RNA-based vaccines were shown to elicit antigen-specific antibody and cellular immune responses against several pathogens (44,(48)(49)(50)(51), the self-amplifying nature of replicon-based vaccines is likely to result in higher levels of antigen expression and in a more effective engagement of innate immune responses than mRNA-based vaccine candidates.…”

Developments in cancer vaccines for hepatocellular carcinoma

“…Both the "off-the-shelf" and the personalized vaccine will be combined with a novel and potent RNA-based immunomodulator (RNAdjuvant ® ) which is based on a noncoding, long-chain RNA molecule able to induce balanced, long-lasting immune responses resulting in a strong anti-tumor activity [53]. Each HCC tumors will be analyzed straight after surgery for expression of tumor-specific HLA ligands, and patient-specific peptides will be selected and synthesized de novo.…”