Multivalent Exosome based protein vaccine: a "mix and match" approach to epidemic viruses' challenges. (preprint)

Endemic viruses are becoming increasingly the norm, and the development of a rapid and effective vaccine is emergent. Here, we used our StealthX TM exosome platform to express either Influenza H3 (StealthTM X-Hemagglutinin, STX-H3) or SARS-CoV-2 Delta spike (StealthTM X-Spike, STX-S) protein on the surface and facilitate their trafficking to the exosomes. When administered as single product, both STX-H3 and STX-S induced a strong immunization with the production of a potent humoral and cellular immune response in mice. Interestingly, these effects were obtained with administration of nanograms of protein and without adjuvant. Therefore, we tested the possibility of a multivalent vaccine: STX-H3 and STX-S exosomes were formulated together in a "mix and match" approach and the immune response was further evaluated. We showed that our STX-H3+S cocktail vaccine is as effective as the single components administered separately, resulting in a strong antibody and T-cell response. Our data show that our exosome platform has an enormous potential to revolutionize vaccinology by rapidly facilitating antigen presentation, and for therapeutics by enabling cell and tissue specific targeting.

Nanograms of SARS-CoV-2 Spike Protein Delivered by Exosomes Induce Potent Neutralization of Both Delta and Omicron Variants. (preprint)

Exosomes are emerging as potent and safe delivery carriers for use in vaccinology and therapeutics. A better vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to provide improved, broader, longer lasting neutralization of SARS-CoV-2, a more robust T cell response, enable widespread global usage, and further enhance the safety profile of vaccines given the likelihood of repeated booster vaccinations. Here, we use Capricor's StealthXTM platform to engineer exosomes to express native SARS-CoV-2 spike Delta variant (STX-S) protein on the surface for the delivery of a protein-based vaccine for immunization against SARS-CoV-2 infection. The STX-S vaccine induced a strong immunization with the production of a potent humoral immune response as demonstrated by high levels of neutralizing antibody not only against the delta SARS-CoV-2 virus but also two Omicron variants (BA.1 and BA.5), providing broader protection than current mRNA vaccines. Additionally, both CD4+ and CD8+ T cell responses were increased significantly after treatment. Quantification of spike protein by ELISA showed that only nanograms of protein were needed to induce a potent immune response. This is a significantly lower dose than traditional recombinant protein vaccines with no adjuvant required, which makes the StealthXTM exosome platform ideal for the development of multivalent vaccines with a better safety profile. Importantly, our exosome platform allows novel proteins, or variants in the case of SARS-CoV-2, to be engineered onto the surface of exosomes in a matter of weeks, comparable with mRNA vaccine technology, but without the cold storage requirements. The ability to utilize exosomes for cellular delivery of proteins, as demonstrated by STX-S, has enormous potential to revolutionize vaccinology by rapidly facilitating antigen presentation at an extremely low dose resulting in a potent, broad antibody response.

Exosome based multivalent vaccine: achieving potent immunization, broaden reactivity and T cell response with nanograms of proteins without any adjuvant. (preprint)

Exosome based vaccines represent an interesting opportunity in the pandemic time we live. Compared to the available vaccines, an exosome-based vaccine may answer to the need of efficacy and increased safety. Here, we used exosomes to deliver a "cocktail" protein-based vaccine, in which two independent viral proteins are delivered using the exosome membrane as carrier. Cells were engineered to express either SARS-CoV-2 Delta spike (StealthTM X-Spike, STX-S) or nucleocapsid (StealthTM X-Nucleocapsid, STX-N) protein on the surface and facilitate their trafficking to the exosomes. When administered as single product, both STX-S and STX-N induced a strong immunization with the production of a potent humoral and cellular immune response. Interestingly, these effects are obtained with administration of nanograms of protein and without adjuvant. Therefore, we developed a multivalent low dose vaccine, namely STX-S+N, using a teeter-toother dose approach of STX-S and STX-N. In two independent animal models (mouse and rabbit), administration of STX-S+N resulted in increased antibody production, potent neutralizing antibodies with cross-reactivity to other VOC and strong T-cell response. Importantly, no competition in immune response was observed. Our data show that our exosome platform has an enormous potential to revolutionize vaccinology by rapidly facilitating antigen presentation, and for therapeutics by enabling cell and tissue specific targeting.