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 C. 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 -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.

Virus-Like Particles Are Efficient Tools for Boosting mRNA-Induced Antibodies

“…We have designed different heterologous vaccination regimens using mRNA-1273 vaccine (Moderna ® ) and our newly developed mosaic COVID-19 VLPs-based vaccine mCuMV TT -RBM ( 17 ) as illustrated in Figure 1A . For SARS-CoV-2 specific genetic vaccine, the mRNA provides expression of the spike protein of COVID-19 ( 20 ).…”

“…There are currently three VLP-based vaccines which have also been tested for COVID-19 in preclinical and clinical trials ( 15 ). The traditional vaccine platforms have shown lower incidence of adverse side effects ( 16 ); however they typically also showed inferior immunogenicity in comparison to the next-generation mRNA vaccines ( 17 – 19 ).…”

“…In the current study, we evaluated different prime and boost regimens combining mRNA-1273 with a VLP-based vaccine based, namely mCuMV TT -RBM. We have previously designed and developed the scalable and immunogenic VLP-based COVID-19 vaccine mCuMV TT -RBM, which has been shown to induce RBD-specific IgG and IgA antibodies with strong neutralizing capability ( 17 ). We show that priming and boosting with mRNA-1273 or mCuMV TT -RBM induced high levels of high avidity antibodies.…”

Increased receptor affinity and reduced recognition by specific antibodies contribute to immune escape of SARS-CoV-2 variant Omicron

“…Importantly, the Delta VOC does not exhibit a mutation at position E484, which is usually associated with strong reduction of recognition by antibodies (9)(10)(11).…”

“…Computational in silico modeling raised concerns about a possible ability of Omicron to dodge antibody-mediated immunity (15). Several reasons may account for the reduced ability of antibodies to neutralize emerging VOCs, including specificity alteration of antibody recognition (classical antibody specificity escape) as well as increased RBD-ACE2 affinity that partially outcompetes antibody binding (affinity escape) (10,11,16,17). So far it seems clear that alteration of antibody recognition of Omicron is related to its E484A mutation (11,(17)(18)(19).…”