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Protein Vaccine Induces a Durable, More Broadly Neutralizing Antibody Response in Macaques than Natural Infection with SARS-CoV-2 P.1

Albert To, Teri Ann S. Wong, Michael M. Lieberman, Karen Thompson, Laurent Pessaint, Jack Greenhouse, Nisrine Daham, Anthony Cook, Brandon Narvaez, Zack Flinchbaugh, Alex Van Ry, Jake Yalley-Ogunro, Hanne Andersen Elyard, Chih-Yun Lai, Oreola Donini, Axel T. Lehrer
doi: https://doi.org/10.1101/2021.09.24.461759
Albert To
1Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School of Medicine, University of Hawai‘i at Mānoa, Honolulu, HI, USA
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Teri Ann S. Wong
1Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School of Medicine, University of Hawai‘i at Mānoa, Honolulu, HI, USA
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Michael M. Lieberman
1Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School of Medicine, University of Hawai‘i at Mānoa, Honolulu, HI, USA
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Karen Thompson
2Department of Pathology, John A. Burns School of Medicine, University of Hawai‘i at Mānoa, Honolulu, HI, USA
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Laurent Pessaint
3Bioqual Inc., Rockville, MD, USA
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Jack Greenhouse
3Bioqual Inc., Rockville, MD, USA
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Nisrine Daham
3Bioqual Inc., Rockville, MD, USA
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Anthony Cook
3Bioqual Inc., Rockville, MD, USA
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Brandon Narvaez
3Bioqual Inc., Rockville, MD, USA
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Zack Flinchbaugh
3Bioqual Inc., Rockville, MD, USA
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Alex Van Ry
3Bioqual Inc., Rockville, MD, USA
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Jake Yalley-Ogunro
3Bioqual Inc., Rockville, MD, USA
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Hanne Andersen Elyard
3Bioqual Inc., Rockville, MD, USA
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Chih-Yun Lai
1Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School of Medicine, University of Hawai‘i at Mānoa, Honolulu, HI, USA
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Oreola Donini
4Soligenix, Inc, Princeton, NJ, USA
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Axel T. Lehrer
1Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School of Medicine, University of Hawai‘i at Mānoa, Honolulu, HI, USA
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  • For correspondence: lehrer@hawaii.edu
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Abstract

FDA-approved and Emergency Use Authorized (EUA) vaccines using new mRNA and viral-vector technology are highly effective in preventing moderate to severe disease, however, information on their long-term efficacy and protective breadth against SARS-CoV-2 Variants of Concern (VOCs) is currently scarce. Here we describe the durability and broad-spectrum VOC immunity of a prefusion-stabilized spike (S) protein adjuvanted with liquid or lyophilized CoVaccine HT™ in cynomolgus macaques. This recombinant subunit vaccine is highly immunogenic and induces robust spike-specific and broadly neutralizing antibody responses effective against circulating VOCs (B.1.351 [Beta], P.1 [Gamma], B.1.617 [Delta]) for at least 3 months after the final boost. Protective efficacy and post-exposure immunity were evaluated using a heterologous P.1 challenge nearly 3 months after the last immunization. Our results indicate that while immunization with both high and low S doses shorten and reduce viral loads in the upper and lower respiratory tract, a higher antigen dose is required to provide durable protection against disease as vaccine immunity wanes. Histologically, P.1 infection causes similar COVID-19-like lung pathology as seen with early pandemic isolates. Post-challenge IgG concentrations were restored to peak immunity levels and vaccine-matched and cross-variant neutralizing antibodies were significantly elevated in immunized macaques indicating an efficient anamnestic response. Only low levels of P.1-specific neutralizing antibodies with limited breadth were observed in control (non-vaccinated but challenged) macaques suggesting that natural infection may not prevent reinfection by other VOCs. Overall, these results demonstrate that a properly dosed and adjuvanted recombinant subunit vaccine can provide long-lasting and protective immunity against circulating VOCs.

One Sentence Summary A recombinant subunit protein formulated with CoVaccine HT™ adjuvant induces superior immunity than natural infection and reduces viral load while protecting cynomolgus macaques from COVID-19-like disease caused by late SARS-CoV-2 P.1 (Gamma) challenge.

Competing Interest Statement

ATL and OD are named inventors on a patent application covering a recombinant subunit vaccine for SARS-CoV-2. LP, JG, ND, AC, BN, ZF, AVR, JYO and HA are current employees of BIOQUAL, Inc. OD is a current employee of Soligenix Inc. All other authors declare no competing interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 25, 2021.
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Protein Vaccine Induces a Durable, More Broadly Neutralizing Antibody Response in Macaques than Natural Infection with SARS-CoV-2 P.1
Albert To, Teri Ann S. Wong, Michael M. Lieberman, Karen Thompson, Laurent Pessaint, Jack Greenhouse, Nisrine Daham, Anthony Cook, Brandon Narvaez, Zack Flinchbaugh, Alex Van Ry, Jake Yalley-Ogunro, Hanne Andersen Elyard, Chih-Yun Lai, Oreola Donini, Axel T. Lehrer
bioRxiv 2021.09.24.461759; doi: https://doi.org/10.1101/2021.09.24.461759
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Protein Vaccine Induces a Durable, More Broadly Neutralizing Antibody Response in Macaques than Natural Infection with SARS-CoV-2 P.1
Albert To, Teri Ann S. Wong, Michael M. Lieberman, Karen Thompson, Laurent Pessaint, Jack Greenhouse, Nisrine Daham, Anthony Cook, Brandon Narvaez, Zack Flinchbaugh, Alex Van Ry, Jake Yalley-Ogunro, Hanne Andersen Elyard, Chih-Yun Lai, Oreola Donini, Axel T. Lehrer
bioRxiv 2021.09.24.461759; doi: https://doi.org/10.1101/2021.09.24.461759

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