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Alum:CpG adjuvant enables SARS-CoV-2 RBD-induced protection in aged mice and synergistic activation of human elder type 1 immunity

Authors :
Etsuro Nanishi
Francesco Borriello
Timothy R. O’Meara
Marisa E. McGrath
Yoshine Saito
Robert E. Haupt
Hyuk-Soo Seo
Simon D. van Haren
Byron Brook
Jing Chen
Joann Diray-Arce
Simon Doss-Gollin
Maria De Leon
Katherine Chew
Manisha Menon
Kijun Song
Andrew Z. Xu
Timothy M. Caradonna
Jared Feldman
Blake M. Hauser
Aaron G. Schmidt
Amy C. Sherman
Lindsey R. Baden
Robert K. Ernst
Carly Dillen
Stuart M. Weston
Robert M. Johnson
Holly L. Hammond
Romana Mayer
Allen Burke
Maria E. Bottazzi
Peter J. Hotez
Ulrich Strych
Aiquan Chang
Jingyou Yu
Dan H. Barouch
Sirano Dhe-Paganon
Ivan Zanoni
Al Ozonoff
Matthew B. Frieman
Ofer Levy
David J. Dowling
Source :
bioRxiv
Publication Year :
2021
Publisher :
Cold Spring Harbor Laboratory, 2021.

Abstract

Global deployment of vaccines that can provide protection across several age groups is still urgently needed to end the COVID-19 pandemic especially for low- and middle-income countries. While 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 needed to meet global demand. In this context, protein subunit vaccines formulated with appropriate adjuvants represent a promising approach to address this urgent need. Receptor-binding domain (RBD) is a key target of neutralizing antibodies (Abs) but is poorly immunogenic. We therefore compared pattern recognition receptor (PRR) agonists, including those activating STING, TLR3, TLR4 and TLR9, alone or formulated with aluminum hydroxide (AH), and benchmarked them to AS01B and AS03-like emulsion-based adjuvants for their potential to enhance RBD immunogenicity in young and aged mice. We found that the AH and CpG adjuvant formulation (AH:CpG) demonstrated the highest enhancement of anti-RBD neutralizing Ab titers in both age groups (∼80-fold over AH), and protected aged mice from the SARS-CoV-2 challenge. Notably, AH:CpG-adjuvanted RBD vaccine elicited neutralizing Abs against both wild-type SARS-CoV-2 and B.1.351 variant at serum concentrations comparable to those induced by the authorized mRNA BNT162b2 vaccine. AH:CpG induced similar cytokine and chemokine gene enrichment patterns in the draining lymph nodes of both young adult and aged mice and synergistically enhanced cytokine and chemokine production in human young adult and elderly mononuclear cells. These data support further development of AH:CpG-adjuvanted RBD as an affordable vaccine that may be effective across multiple age groups.One Sentence SummaryAlum and CpG enhance SARS-CoV-2 RBD protective immunity, variant neutralization in aged mice and Th1-polarizing cytokine production by human elder leukocytes.

Details

Database :
OpenAIRE
Journal :
bioRxiv
Accession number :
edsair.doi.dedup.....793e7db59466c2860e1fcf3d8e466c19