New Kids on the Block: RNA-Based Influenza Virus Vaccines

Abstract

RNA-based immunization strategies have emerged as promising alternatives to conventional vaccine approaches. A substantial body of published work demonstrates that RNA vaccines can elicit potent, protective immune responses against various pathogens. Consonant with its huge impact on public health, influenza virus is one of the best studied targets of RNA vaccine research. Currently licensed influenza vaccines show variable levels of protection against seasonal influenza virus strains but are inadequate against drifted and pandemic viruses. In recent years, several types of RNA vaccines demonstrated efficacy against influenza virus infections in preclinical models. Additionally, comparative studies demonstrated the superiority of some RNA vaccines over the currently used inactivated influenza virus vaccines in animal models. Based on these promising preclinical results, clinical trials have been initiated and should provide valuable information about the translatability of the impressive preclinical data to humans. This review briefly describes RNA-based vaccination strategies, summarizes published preclinical and clinical data, highlights the roadblocks that need to be overcome for clinical applications, discusses the landscape of industrial development, and shares the authors’ personal perspectives about the future of RNA-based influenza virus vaccines.

Influenza vaccine: Where are we and where do we go?

“…The capability of RNA vaccines to trigger strong, protective immune responses against a wide spectrum of pathogens has led to a large number of studies focusing on the use of these vaccines against influenza virus. As recently approved influenza vaccines demonstrated variable and inadequate protection, a promising efficacy has been shown for several more recently RNA vaccines types in preclinical models …”

“…Single‐stranded oligoribonucleotides and the products of their degradation are recognized by the endosomal sensors Toll‐like receptor 7 (TLR7) and TLR8, leading to type I interferon production . In addition, trivalent saRNA (small activating RNAs) vaccination could result in anti‐H1N1 and H3N2 IgG responses …”

“…96 In addition, trivalent saRNA (small activating RNAs) vaccination could result in anti-H1N1 and H3N2 IgG responses. 97 A number of delivery formulation platforms have been explained to enhance the RNA vaccination, including PEI-based delivery vehicles. 95 protective immunity against various infectious agents in preclinical models.…”

mRNA Vaccines Encoding the HA Protein of Influenza A H1N1 Virus Delivered by Cationic Lipid Nanoparticles Induce Protective Immune Responses in Mice

“…The two main types of RNA vaccines used against influenza viruses are self-amplified mRNA (SAM) vaccine and nonreplicating mRNA vaccine. A pioneering work showed that intramuscular injection of SAM encoding the HA gene in A/California/07/2009, combined with oil-in-water nanoemulsions, could protect mice and ferrets from homologous and heterogeneous influenza viruses [4,14]. Barr and colleagues provided evidence that a single intradermal immunization with a 10-µg mRNA vaccine encoding the nucleoside-modified HA gene of H10N8 or H7N9 led to the production of HA antibodies in mice for more than a year.…”

“…Barr and colleagues provided evidence that a single intradermal immunization with a 10-µg mRNA vaccine encoding the nucleoside-modified HA gene of H10N8 or H7N9 led to the production of HA antibodies in mice for more than a year. Phase I clinical trials (NCT03076385) using this platform were launched due to promising preclinical results [14,15].…”