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Directing an mRNA-LNP vaccine toward lymph nodes improves humoral and cellular immunity against SARS-CoV-2

David M. Francis, Runqiang Chen, Sahba Khorsandzadeh, Qidong Hu, Xiaoxuan Lyu, Hua Wang, Wan-lin Lim, Haotian Sun, Hui Xie, Namir Shaabani, Russell Ross, Brian Cooley, Henry Ji
doi: https://doi.org/10.1101/2021.08.25.457699
David M. Francis
1Sorrento Therapeutics, Inc., San Diego, CA 92121
2Sofusa, a Division of Sorrento Therapeutics, Atlanta, GA 30350
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  • For correspondence: dfrancis@sorrentotherapeutics.com
Runqiang Chen
1Sorrento Therapeutics, Inc., San Diego, CA 92121
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Sahba Khorsandzadeh
1Sorrento Therapeutics, Inc., San Diego, CA 92121
2Sofusa, a Division of Sorrento Therapeutics, Atlanta, GA 30350
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Qidong Hu
1Sorrento Therapeutics, Inc., San Diego, CA 92121
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Xiaoxuan Lyu
1Sorrento Therapeutics, Inc., San Diego, CA 92121
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Hua Wang
1Sorrento Therapeutics, Inc., San Diego, CA 92121
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Wan-lin Lim
1Sorrento Therapeutics, Inc., San Diego, CA 92121
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Haotian Sun
1Sorrento Therapeutics, Inc., San Diego, CA 92121
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Hui Xie
1Sorrento Therapeutics, Inc., San Diego, CA 92121
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Namir Shaabani
1Sorrento Therapeutics, Inc., San Diego, CA 92121
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Russell Ross
1Sorrento Therapeutics, Inc., San Diego, CA 92121
2Sofusa, a Division of Sorrento Therapeutics, Atlanta, GA 30350
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Brian Cooley
1Sorrento Therapeutics, Inc., San Diego, CA 92121
2Sofusa, a Division of Sorrento Therapeutics, Atlanta, GA 30350
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Henry Ji
1Sorrento Therapeutics, Inc., San Diego, CA 92121
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Abstract

The exploration and identification of safe and effective vaccines for the SARS-CoV-2 pandemic has captured the world’s attention and remains an ongoing issue in order to protect against emerging variants of concern (VoCs) while generating long lasting immunity. Here, we report the synthesis of a novel messenger ribonucleic acid (mRNA) encoding the spike protein in a lipid nanoparticle formulation (LNP) (STI-7264) that generates robust humoral and cellular immunity following immunization of C57Bl6 mice. In efforts to continually improve immunity, a lymphatic drug delivery device (MuVaxx) was engineered and tested to modulate immune cells at the injection site (epidermis and dermis) and draining lymph node (LN) to elicit adaptive immunity. Using MuVaxx, immune responses were elicited and maintained at a 10-fold dose reduction compared to traditional intramuscular (IM) administration as measured by anti-spike antibodies, cytokine producing CD8 T cells, and neutralizing antibodies against the Washington (Wild Type, WT) and South African (beta) variants. Remarkably, a 4-fold elevated T cell response was observed in MuVaxx administered vaccination as compared to that of IM administered vaccination. Thus, these data support further investigation into STI-7264 and lymphatic mediated delivery using MuVaxx for SARS-CoV-2 and VoCs vaccines.

Competing Interest Statement

Sorrento authors own options and/or stock of the company. This work has been described in one or more provisional patent applications. HJ is an officer at Sorrento Therapeutics, Inc..

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted August 25, 2021.
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Directing an mRNA-LNP vaccine toward lymph nodes improves humoral and cellular immunity against SARS-CoV-2
David M. Francis, Runqiang Chen, Sahba Khorsandzadeh, Qidong Hu, Xiaoxuan Lyu, Hua Wang, Wan-lin Lim, Haotian Sun, Hui Xie, Namir Shaabani, Russell Ross, Brian Cooley, Henry Ji
bioRxiv 2021.08.25.457699; doi: https://doi.org/10.1101/2021.08.25.457699
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Directing an mRNA-LNP vaccine toward lymph nodes improves humoral and cellular immunity against SARS-CoV-2
David M. Francis, Runqiang Chen, Sahba Khorsandzadeh, Qidong Hu, Xiaoxuan Lyu, Hua Wang, Wan-lin Lim, Haotian Sun, Hui Xie, Namir Shaabani, Russell Ross, Brian Cooley, Henry Ji
bioRxiv 2021.08.25.457699; doi: https://doi.org/10.1101/2021.08.25.457699

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