1. Carbohydrate fatty acid monosulphate: oil-in-water adjuvant enhances SARS-CoV-2 RBD nanoparticle-induced immunogenicity and protection in mice
- Author
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Etsuro Nanishi, Francesco Borriello, Hyuk-Soo Seo, Timothy R. O’Meara, Marisa E. McGrath, Yoshine Saito, Jing Chen, Joann Diray-Arce, Kijun Song, Andrew Z. Xu, Soumik Barman, Manisha Menon, Danica Dong, Timothy M. Caradonna, Jared Feldman, Blake M. Hauser, Aaron G. Schmidt, Lindsey R. Baden, Robert K. Ernst, Carly Dillen, Jingyou Yu, Aiquan Chang, Luuk Hilgers, Peter Paul Platenburg, Sirano Dhe-Paganon, Dan H. Barouch, Al Ozonoff, Ivan Zanoni, Matthew B. Frieman, David J. Dowling, and Ofer Levy
- Subjects
Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Development of SARS-CoV-2 vaccines that protect vulnerable populations is a public health priority. Here, we took a systematic and iterative approach by testing several adjuvants and SARS-CoV-2 antigens to identify a combination that elicits antibodies and protection in young and aged mice. While demonstrating superior immunogenicity to soluble receptor-binding domain (RBD), RBD displayed as a protein nanoparticle (RBD-NP) generated limited antibody responses. Comparison of multiple adjuvants including AddaVax, AddaS03, and AS01B in young and aged mice demonstrated that an oil-in-water emulsion containing carbohydrate fatty acid monosulphate derivative (CMS:O/W) most effectively enhanced RBD-NP-induced cross-neutralizing antibodies and protection across age groups. CMS:O/W enhanced antigen retention in the draining lymph node, induced injection site, and lymph node cytokines, with CMS inducing MyD88-dependent Th1 cytokine polarization. Furthermore, CMS and O/W synergistically induced chemokine production from human PBMCs. Overall, CMS:O/W adjuvant may enhance immunogenicity and protection of vulnerable populations against SARS-CoV-2 and other infectious pathogens.
- Published
- 2023
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