Speeding up vaccine development
Vaccine platform technology
BunyaVax develops versatile vaccine platform technologies for generating safe and efficacious vaccines against infectious diseases.
The BunyaVax RNA platform is based on a nonspreading bunyavirus that can be tailor-made to express a protein from a heterologous pathogen. Vaccination results in infection of single cells that triggers strong innate and adaptive immune reponses.
The Bunya LIVE technology is used to develop next-generation live-attenuated vaccines against emerging and re-emerging bunyaviruses, such as Rift Valley fever virus.
The proprietary Bunya RNA platform is based on bunyavirus-based RNA particles. These particles are highly infectious for many cell types and are potent stimulators of innate and adaptive immune responses. (Kortekaas et al J Virol 2011). The particles resemble authentic viruses, but are incapable of autonomous spreading, rendering their application inherently safe. This combination makes them suitable for the development of a much-needed new generation of vaccines that optimally combines safety with efficacy.
A unique characteristic of the platform is that it allows for ‘plug and play’ application. Any gene can be plugged into the RNA particle genome in a straightforward process to rapidly generate vaccines against newly emerging viruses. The principle is as follows (see also schematic representation below). Firstly, a gene encoding an immunogenic protein is selected from the pathogen of interest (for example the hemagglutinin gene of influenza virus). Secondly, the selected gene is used to develop customized replicon cells, stably maintaining the selected gene in Bunyavirus RNA segments. After introducing a single packaging plasmid via either transfection or electroporation, the RNA particles will be produced. This process can be completed in a timeframe of several weeks.
The technology underlying the Bunya RNA platform has been developed by the group of Jeroen Kortekaas and has been described in multiple peer reviewed scientific journals. These studies demonstrated vaccine efficacy and safety in three separate settings:
A single intramuscular vaccination protected sheep from virulent RVFV (Oreshkova et al., PLoS ONE, 2013).
Mice that received a single vaccination of RNA particles expressing influenza virus hemagglutinin were protected from a lethal challenge dose (Oreshkova et al., Vaccine 2014).
RNA particles expressing a single tumor-associated peptide protected mice from tumor outgrowth both prophylactically and therapeutically. (Oreshkova et al., Journal of Virology 2015).
BunyaVax applies its Bunya LIVE platform technology to create safe live-attenuated vaccines against bunyaviruses such as Rift Valley Fever. Live-attenuated vaccines hold great promise, as these vaccines can be produced cost-effectively and generally provide long-lasting protection after a single vaccination.
The Bunya LIVE technology is based on an avirulent Rift Valley fever virus (RVFV). This avirulent RVFV was developed previously by splitting the M genome segment of the virus into two separate segments. This resulted in a four-segmented RVFV (RVFV-4s). RVFV-4s was shown to be completely avirulent in the most susceptible target animals. To optimize vaccine safety, the NSs protein, which is the major virulence factor of the virus, was removed from the genome. The resulting live-attenuated virus can be designed to express a gene of interest.
Excellent efficacy and safety of Bunya LIVE vaccines was demonstrated by:
Induction of sterile immunity after a single vaccination of lambs.
Safety after administration of an overdose to ewes during the first trimester of gestation.
Creation of a nonspreading Rift Valley fever virus. Kortekaas J, Oreshkova N, Cobos-Jiménez V, Vloet RP, Potgieter CA, Moormann RJM. J Virol. 2011 Dec;85(23):12622-30.
Efficacy of three candidate Rift Valley fever vaccines in sheep. Kortekaas J, Antonis AF, Kant J, Vloet RP, Vogel A, Oreshkova N, de Boer SM, Bosch BJ, Moormann RJM. Vaccine. 2012 30:3423-3429.
A single vaccination with an improved nonspreading Rift Valley fever virus vaccine provides sterile immunity in lambs. Oreshkova N, van Keulen L, Kant J, Moormann RJ, Kortekaas J. PLoS One. 2013 Oct 22;8(10):e77461.
Creation of Rift Valley fever viruses with four-segmented genomes reveals flexibility in bunyavirus genome packaging. Wichgers Schreur PJ, Oreshkova N, Moormann RJ, Kortekaas J. J Virol. 2014;88(18):10883-93.
Comparative efficacy of two next-generation Rift Valley fever vaccines. Kortekaas J, Oreshkova N, van Keulen L, Kant J, Bosch BJ, Bouloy M, Moulin V, Goovaerts D, Moormann RJ. Vaccine. 2014 Sep 3;32(39):4901-8.
Evaluation of nonspreading Rift Valley fever virus as a vaccine vector using influenza virus hemagglutinin as a model antigen. Oreshkova N, Cornelissen LA, de Haan CA, Moormann RJ, Kortekaas J. Vaccine. 2014;32(41):5323-9.
Four-segmented Rift Valley fever virus induces sterile immunity in sheep after a single vaccination. Wichgers Schreur PJ, Kant J, van Keulen L, Moormann RJ, Kortekaas J. Vaccine. 2015 Mar 17;33(12):1459-64.
Preliminary Evaluation of a Bunyavirus Vector for Cancer Immunotherapy. Oreshkova N, Spel L, Vloet RP, Schreur PJ, Moormann RJ, Boes M, Kortekaas J. J Virol. 2015 Jun 17. pii: JVI.01105-15.
Four-segmented Rift Valley fever virus-based vaccines can be applied safely in ewes during pregnancy. Wichgers Schreur PJ, van Keulen L, Kant J, Kortekaas J. Vaccine. 2017;35:3123-3128.
A novel highly sensitive, rapid and safe Rift Valley fever virus neutralization test. Wichgers Schreur PJ, Paweska JT, Kant J, Kortekaas J. J Virol Methods. 2017 Oct;248:26-30.