DNA-launched RNA replicon vaccines induce potent anti-Ebolavirus immune responses that can be further improved by a recombinant MVA boost

Öhlund, Pontus; García-Arriaza, Juan; Žusinaite, Eva; Szurgot, Inga; Männik, Andres; Kraus, Annette; Ustav, Mart; Merits, Andres; Esteban, Mariano; Liljeström, Peter; Ljungberg, Karl

doi:10.1038/s41598-018-31003-6

Cited by 24 publications

(21 citation statements)

References 58 publications

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“…Antimycin A is a prominent broad-spectrum antiviral that inhibits the cellular mitochondrial electron transport chain and de novo pyrimidine synthesis [67]. Besides drug discovery, togavirus replicons have been modified and successfully used as platforms for the expression of heterologous recombinant proteins and as vaccine platforms [68][69][70][71].…”

Section: Togavirus Repliconsmentioning

confidence: 99%

Viral replicons as valuable tools for drug discovery

Hannemann¹

2020

Drug Discovery Today

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RNA viruses can cause severe diseases such as dengue, Lassa, chikungunya and Ebola. Many of these viruses can only be propagated under high containment levels, necessitating the development of low containment surrogate systems such as subgenomic replicons and minigenome systems. Replicons are self-amplifying recombinant RNA molecules expressing proteins sufficient for their own replication but which do not produce infectious virions. Replicons can persist in cells and are passed on during cell division, enabling quick, efficient and high-throughput testing of drug candidates that act on viral transcription, translation and replication. This review will explore the history and potential for drug discovery of hepatitis C virus, dengue virus, respiratory syncytial virus, Ebola virus and norovirus replicon and minigenome systems.

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Section: Togavirus Repliconsmentioning

confidence: 99%

Viral replicons as valuable tools for drug discovery

Hannemann¹

2020

Drug Discovery Today

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“…However, both mice and guinea pigs coimmunized with VEE-EBOV-GP and VEE-EBOV-NP were resistant to EBOV challenges. In another approach, coexpression of EBOV-GP and EBOV-VP40 from SFV DNA replicons elicited both binding and neutralizing antibodies of higher titers compared to a Modified Vaccinia virus Ankara (MVA) vaccine [60].…”

Section: Application Of Self-amplifying Rnas As Vaccines Against Infementioning

confidence: 99%

The Potential of Self-amplifying RNA Vaccines for Infectious Diseases and COVID-19

Lundström

2020

vacres

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In addition to conventional vaccine development for infectious diseases, nucleic acidbased vaccine approaches have recently been presented as serious alternatives to previously used strategies based on live attenuated virus particles and subunit vaccines. Particularly, RNA-based vaccines have proven attractive. In this context, immunization with messenger RNA (mRNA) has provided strong immune responses and protection against challenges with lethal doses of pathogenic viruses in vaccinated animals. Alternatively, the efficient RNA replication mechanism provided by self-amplifying RNA (saRNA) viruses has been utilized. Enhanced immune responses with reduced doses required for immunization has been obtained in comparison to conventional mRNA administration. The rapid spread and destruction caused by the COVID-19 pandemic has substantially accelerated the demand for the development of robust and efficient vaccines against SARS-CoV-2. Both mRNA-and saRNA-based COVID-19 vaccine candidates are currently in human clinical trials.

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“…A bivalent DREP vaccine expressing EBOV GP and SUDV GP elicited similar levels of anti-GP IgG in mice. 70 The protective efficacy of the DREP vectored vaccines remain to be tested.…”

Section: Replication Incompetent Vaccinesmentioning

confidence: 99%

Vaccines against Ebola virus and Marburg virus: recent advances and promising candidates

Suschak

Schmaljohn

2019

Human Vaccines & Immunotherapeutics

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The filoviruses Ebola virus and Marburg virus are among the most dangerous pathogens in the world. Both viruses cause viral hemorrhagic fever, with case fatality rates of up to 90%. Historically, filovirus outbreaks had been relatively small, with only a few hundred cases reported. However, the recent West African Ebola virus outbreak underscored the threat that filoviruses pose. The three year-long outbreak resulted in 28,646 Ebola virus infections and 11,323 deaths. The lack of Food and Drug Administration (FDA) licensed vaccines and antiviral drugs hindered early efforts to contain the outbreak. In response, the global scientific community has spurred the advanced development of many filovirus vaccine candidates. Novel vaccine platforms, such as viral vectors and DNA vaccines, have emerged, leading to the investigation of candidate vaccines that have demonstrated protective efficacy in small animal and nonhuman primate studies. Here, we will discuss several of these vaccine platforms with a particular focus on approaches that have advanced into clinical development.

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DNA-launched RNA replicon vaccines induce potent anti-Ebolavirus immune responses that can be further improved by a recombinant MVA boost

Cited by 24 publications

References 58 publications

Viral replicons as valuable tools for drug discovery

Viral replicons as valuable tools for drug discovery

The Potential of Self-amplifying RNA Vaccines for Infectious Diseases and COVID-19

Vaccines against Ebola virus and Marburg virus: recent advances and promising candidates

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