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    An aluminum hydroxide:CpG adjuvant enhances protection elicited by a SARS-CoV-2 receptor binding domain vaccine in aged mice.

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    Author
    Nanishi, Etsuro
    Borriello, Francesco
    O'Meara, Timothy R
    McGrath, Marisa E
    Saito, Yoshine
    Haupt, Robert E
    Seo, Hyuk-Soo
    van Haren, Simon D
    Cavazzoni, Cecilia B
    Brook, Byron
    Barman, Soumik
    Chen, Jing
    Diray-Arce, Joann
    Doss-Gollin, Simon
    De Leon, Maria
    Prevost-Reilly, Alejandra
    Chew, Katherine
    Menon, Manisha
    Song, Kijun
    Xu, Andrew Z
    Caradonna, Timothy M
    Feldman, Jared
    Hauser, Blake M
    Schmidt, Aaron G
    Sherman, Amy C
    Baden, Lindsey R
    Ernst, Robert K
    Dillen, Carly
    Weston, Stuart M
    Johnson, Robert M
    Hammond, Holly L
    Mayer, Romana
    Burke, Allen
    Bottazzi, Maria E
    Hotez, Peter J
    Strych, Ulrich
    Chang, Aiquan
    Yu, Jingyou
    Sage, Peter T
    Barouch, Dan H
    Dhe-Paganon, Sirano
    Zanoni, Ivan
    Ozonoff, Al
    Frieman, Matthew B
    Levy, Ofer
    Dowling, David J
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    Date
    2022-01-26
    Journal
    Science Translational Medicine
    Publisher
    American Association for the Advancement of Science
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1126/scitranslmed.abj5305
    Abstract
    Global deployment of vaccines that can provide protection across several age groups is still urgently needed to end the COVID-19 pandemic, especially in low- and middle-income countries. Although vaccines against SARS-CoV-2 based on mRNA and adenoviral vector technologies have been rapidly developed, additional practical and scalable SARS-CoV-2 vaccines are required to meet global demand. Protein subunit vaccines formulated with appropriate adjuvants represent an approach to address this urgent need. The receptor binding domain (RBD) is a key target of SARS-CoV-2 neutralizing antibodies but is poorly immunogenic. We therefore compared pattern recognition receptor (PRR) agonists alone or formulated with aluminum hydroxide (AH) and benchmarked them against AS01B and AS03-like emulsion-based adjuvants for their potential to enhance RBD immunogenicity in young and aged mice. We found that an AH and CpG adjuvant formulation (AH:CpG) produced an 80-fold increase in anti-RBD neutralizing antibody titers in both age groups relative to AH alone and protected aged mice from the SARS-CoV-2 challenge. The AH:CpG-adjuvanted RBD vaccine elicited neutralizing antibodies against both wild-type SARS-CoV-2 and the B.1.351 (beta) variant at serum concentrations comparable to those induced by the licensed Pfizer-BioNTech BNT162b2 mRNA vaccine. AH:CpG induced similar cytokine and chemokine gene enrichment patterns in the draining lymph nodes of both young adult and aged mice and enhanced cytokine and chemokine production in human mononuclear cells of younger and older adults. These data support further development of AH:CpG-adjuvanted RBD as an affordable vaccine that may be effective across multiple age groups.
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/17909
    ae974a485f413a2113503eed53cd6c53
    10.1126/scitranslmed.abj5305
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    UMB Coronavirus Publications
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