RT Journal Article
SR Electronic
T1 Exosome based multivalent vaccine: achieving potent immunization, broadened reactivity, and strong T cell responses with nanograms of proteins
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.01.10.523356
DO 10.1101/2023.01.10.523356
A1 Mafalda Cacciottolo
A1 Justin B Nice
A1 Yujia Li
A1 Michael J. LeClaire
A1 Ryan Twaddle
A1 Ciana Mora
A1 Stephanie Y. Adachi
A1 Esther R. Chin
A1 Meredith Young
A1 Jenna Angeles
A1 Kristi Elliott
A1 Minghao Sun
YR 2023
UL http://biorxiv.org/content/early/2023/01/19/2023.01.10.523356.abstract
AB Current approved vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused solely on the spike protein to provide immunity. The first vaccines were developed rapidly using spike mRNA delivered by lipid nanoparticles but required ultra-low storage and have had limited immunity against variations in spike. Subsequently, protein-based vaccines were developed which offer broader immunity but require significant time for development and use of an adjuvant to boost immune response. Here, exosomes were used to deliver a bi-valent protein-based vaccine, in which two independent viral proteins were used. Exosomes were engineered to express either SARS-CoV-2 Delta spike (Stealth X-Spike, STX-S) or the more conserved nucleocapsid (Stealth X-Nucleocapsid, STX-N) protein on the surface. When administered as single product (STX-S or STX-N) or in combination (STX-S+N), both STX-S and STX-N induced a strong immunization with the production of a potent humoral and cellular immune response. Interestingly, these results were obtained with administration of only nanograms of protein and without adjuvant. In two independent animal models (mouse and rabbit), administration of nanograms of the STX-S+N vaccine resulted in increased antibody production, potent neutralizing antibodies with cross-reactivity to other variants of spike and strong T-cell responses. Importantly, no competition in immune response was observed, allowing for delivery of nucleocapsid with spike to offer improved SARS-CoV-2 immunity. These data show that the StealthXTM exosome platform has an enormous potential to revolutionize vaccinology by combining the advantages of mRNA and recombinant protein vaccines into a superior, rapidly generated, low dose vaccine resulting in potent, broader immunity.Competing Interest StatementThe authors are employees of Capricor Therapeutics.