An aluminum hydroxide:CpG adjuvant enhances protection elicited by a SARS-CoV-2 receptor binding domain vaccine in aged mice.
Author
Nanishi, EtsuroBorriello, 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
Date
2022-01-26Journal
Science Translational MedicinePublisher
American Association for the Advancement of ScienceType
Article
Metadata
Show full item recordAbstract
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/10713/17909ae974a485f413a2113503eed53cd6c53
10.1126/scitranslmed.abj5305
Scopus Count
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