Self-replicating alphavirus RNA vaccines

Abstract

Recombinant nucleic acids are considered as promising next-generation vaccines. These vaccines express the native antigen upon delivery into tissue, thus mimicking live attenuated vaccines without having the risk of reversion to pathogenicity. They also stimulate the innate immune system, thus potentiating responses. Nucleic acid vaccines are easy to produce at reasonable cost and are stable. During the past years, focus has been on the use of plasmid DNA for vaccination. Now mRNA and replicon vaccines have come into focus as promising technology platforms for vaccine development. This review discusses self-replicating RNA vaccines developed from alphavirus expression vectors. These replicon vaccines can be delivered as RNA, DNA or as recombinant virus particles. All three platforms have been pre-clinically evaluated as vaccines against a number of infectious diseases and cancer. Results have been very encouraging and propelled the first human clinical trials, the results of which have been promising.

Keywords:

• adjuvant
• alphavirus
• electroporation
• prime-boost
• replicon
• RNA vaccine
• self-replicating RNA
• vaccine

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Recombinant self-replicating RNAs (replicons) can be used as vaccines and delivered as RNA, as lipid-formulated RNA, as DNA or as recombinant virus particles.

• Replicon vaccines will express the antigen of interest in tissue, thus mimicking live attenuated vaccines.

• Being derived from RNA viruses, replicons are seen by the immune system as a virus infection, which includes innate stimulatory signals enhancing the potency of these vaccines.

• Replicon vaccines are safe and easy to produce using generic production platforms.

• Numerous pre-clinical studies have underscored the potency of these vaccines against infectious diseases and cancer.

• Replicon vaccines have now entered human clinical trials with very encouraging results.