1. An aluminum hydroxide:CpG adjuvant enhances protection elicited by a SARS-CoV-2 receptor binding domain vaccine in aged mice.
- Author
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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, and Xu, Andrew Z.
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MONONUCLEAR leukocytes ,PATTERN perception receptors ,COVID-19 vaccines ,SARS-CoV-2 ,IMMUNOGLOBULINS ,YOUNG adults ,VACCINES - 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. A vaccine for the ages: Vaccines against SARS-CoV-2 are especially important for protecting older adults who are at the highest risk of developing severe COVID-19. To address this, Nanishi et al. tested a receptor binding domain (RBD) protein subunit vaccine with a variety of adjuvants to find which combination best protected aged mice. The authors found that combining RBD with aluminum hydroxide (AH) and CpG resulted in a highly immunogenic vaccine that was protective in young and aged mice. The authors also showed that AH:CpG induced robust innate immune responses in peripheral blood mononuclear cells isolated from older adults. This vaccine is also scalable and could be deployed to low- and middle-income countries. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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