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A Lymph Node Targeted Amphiphile Vaccine Induces Potent Cellular and Humoral Immunity to SARS-CoV-2

Martin P. Steinbuck, Lochana M. Seenappa, Aniela Jakubowski, Lisa K. McNeil, Christopher M. Haqq, Peter C. DeMuth
doi: https://doi.org/10.1101/2020.08.17.251728
Martin P. Steinbuck
Elicio Therapeutics, One Kendall Square, Suite 14303, Cambridge, MA 02139
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Lochana M. Seenappa
Elicio Therapeutics, One Kendall Square, Suite 14303, Cambridge, MA 02139
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Aniela Jakubowski
Elicio Therapeutics, One Kendall Square, Suite 14303, Cambridge, MA 02139
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Lisa K. McNeil
Elicio Therapeutics, One Kendall Square, Suite 14303, Cambridge, MA 02139
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Christopher M. Haqq
Elicio Therapeutics, One Kendall Square, Suite 14303, Cambridge, MA 02139
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  • For correspondence: chris.haqq@elicio.com
Peter C. DeMuth
Elicio Therapeutics, One Kendall Square, Suite 14303, Cambridge, MA 02139
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Abstract

The SARS-CoV-2 pandemic has led to public health, economic, and social consequences that mandate urgent development of effective vaccines to contain or eradicate infection. To that end, we evaluated a novel amphiphile (AMP) vaccine adjuvant, AMP-CpG, composed of diacyl lipid-modified CpG, admixed with the SARS-CoV-2 Spike-2 receptor binding domain protein as a candidate vaccine (ELI-005) in mice. AMP immunogens are efficiently delivered to lymph nodes, where innate and adaptive immune responses are generated. Compared to alum, AMP immunization induced >25-fold higher antigen-specific T cells which produced multiple Th1 cytokines and trafficked into lung parenchyma and respiratory secretions. Antibody responses favored Th1 isotypes (IgG2bc, IgG3) and potently neutralized Spike-2-ACE2 receptor binding, with titers 265-fold higher than the natural immune response from convalescent COVID-19 patients; responses were maintained despite 10-fold dose-reduction in Spike antigen. Both cellular and humoral immune responses were preserved in aged mice. These advantages merit clinical translation to SARS-CoV-2 and other protein subunit vaccines.

Competing Interest Statement

All authors are employees of Elicio Therapeutics, and as such receive salary and benefits, including ownership of stock and stock options from the company. P.C.D., M.P.S., L.M.S., and C.M.H have an amphiphile SARS-CoV-2 vaccine patent pending to Elicio.

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-ND 4.0 International license.
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Posted August 18, 2020.
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A Lymph Node Targeted Amphiphile Vaccine Induces Potent Cellular and Humoral Immunity to SARS-CoV-2
Martin P. Steinbuck, Lochana M. Seenappa, Aniela Jakubowski, Lisa K. McNeil, Christopher M. Haqq, Peter C. DeMuth
bioRxiv 2020.08.17.251728; doi: https://doi.org/10.1101/2020.08.17.251728
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A Lymph Node Targeted Amphiphile Vaccine Induces Potent Cellular and Humoral Immunity to SARS-CoV-2
Martin P. Steinbuck, Lochana M. Seenappa, Aniela Jakubowski, Lisa K. McNeil, Christopher M. Haqq, Peter C. DeMuth
bioRxiv 2020.08.17.251728; doi: https://doi.org/10.1101/2020.08.17.251728

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