An aluminum hydroxide:CpG adjuvant enhances protection elicited by a SARS-CoV-2 receptor binding domain vaccine in aged mice.
O'Meara, Timothy R
McGrath, Marisa E
Haupt, Robert E
van Haren, Simon D
Cavazzoni, Cecilia B
De Leon, Maria
Xu, Andrew Z
Caradonna, Timothy M
Hauser, Blake M
Schmidt, Aaron G
Sherman, Amy C
Baden, Lindsey R
Ernst, Robert K
Weston, Stuart M
Johnson, Robert M
Hammond, Holly L
Bottazzi, Maria E
Hotez, Peter J
Sage, Peter T
Barouch, Dan H
Frieman, Matthew B
Dowling, David J
JournalScience Translational Medicine
PublisherAmerican Association for the Advancement of Science
MetadataShow full item record
AbstractGlobal 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 itemhttp://hdl.handle.net/10713/17909
- Alum:CpG adjuvant enables SARS-CoV-2 RBD-induced protection in aged mice and synergistic activation of human elder type 1 immunity.
- Authors: Nanishi E, Borriello F, O'Meara TR, McGrath ME, Saito Y, Haupt RE, Seo HS, van Haren SD, Brook B, Chen J, Diray-Arce J, Doss-Gollin S, Leon M, Chew K, Menon M, Song K, Xu AZ, Caradonna TM, Feldman J, Hauser BM, Schmidt AG, Sherman AC, Baden LR, Ernst RK, Dillen C, Weston SM, Johnson RM, Hammond HL, Mayer R, Burke A, Bottazzi ME, Hotez PJ, Strych U, Chang A, Yu J, Barouch DH, Dhe-Paganon S, Zanoni I, Ozonoff A, Frieman MB, Levy O, Dowling DJ
- Issue date: 2021 May 21
- Adjuvanted SARS-CoV-2 spike protein elicits neutralizing antibodies and CD4 T cell responses after a single immunization in mice.
- Authors: Wørzner K, Sheward DJ, Schmidt ST, Hanke L, Zimmermann J, McInerney G, Karlsson Hedestam GB, Murrell B, Christensen D, Pedersen GK
- Issue date: 2021 Jan
- Hydrogel-Based Slow Release of a Receptor-Binding Domain Subunit Vaccine Elicits Neutralizing Antibody Responses Against SARS-CoV-2.
- Authors: Gale EC, Powell AE, Roth GA, Meany EL, Yan J, Ou BS, Grosskopf AK, Adamska J, Picece VCTM, d'Aquino AI, Pulendran B, Kim PS, Appel EA
- Issue date: 2021 Dec
- High-Resolution Linear Epitope Mapping of the Receptor Binding Domain of SARS-CoV-2 Spike Protein in COVID-19 mRNA Vaccine Recipients.
- Authors: Nitahara Y, Nakagama Y, Kaku N, Candray K, Michimuko Y, Tshibangu-Kabamba E, Kaneko A, Yamamoto H, Mizobata Y, Kakeya H, Yasugi M, Kido Y
- Issue date: 2021 Dec 22
- Yeast-expressed SARS-CoV recombinant receptor-binding domain (RBD219-N1) formulated with aluminum hydroxide induces protective immunity and reduces immune enhancement.
- Authors: Chen WH, Tao X, Agrawal AS, Algaissi A, Peng BH, Pollet J, Strych U, Bottazzi ME, Hotez PJ, Lustigman S, Du L, Jiang S, Tseng CK
- Issue date: 2020 Nov 3