A scalable and highly immunogenic virus-like particle-based vaccine
against SARS-CoV-2
Abstract
SARS-CoV-2 caused one of the most devastating pandemics in the recent
history of mankind. Due to various countermeasures, including
lock-downs, wearing masks and increased hygiene, the virus has been
controlled in some parts of the world. More recently, the availability
of vaccines, based on RNA or Adenoviruses, have greatly added to our
ability to keep the virus at bay, again in some parts of the world only.
While available vaccines are effective, it would be desirable to also
have more classical vaccines at hand for the future. Key feature of
vaccines for long-term control of SARS-CoV-2 would be inexpensive
production at large scale, ability to make multiple booster injections
and long-term stability at +4 oC. Here we describe
such a vaccine candidate, consisting of the SARS-CoV-2 receptor binding
motif grafted genetically onto the surface of the immunologically
optimized cucumber mosaic virus, called CuMV TT-RBM.
Using bacterial fermenter production and continuous flow centrifugation,
the productivity of the production process is estimated to be
>2.5 million doses per 1000 liter fermenter run and the
vaccine candidate is stable for at least 14 months at 4°C. We further
demonstrate that the candidate vaccine is highly immunogenic in mice and
rabbits and induces more high avidity antibodies compared to
convalescent human sera and antibodies induced are more cross-reactive
to mutant RBDs for variants of concern (VoC). Furthermore, antibody
responses are neutralizing and long-lived. This, the here presented
VLP-based vaccine may be a good candidate for use as conventional
vaccine in the long-term.