Carbohydrate fatty acid monosulphate: oil-in-water adjuvant enhances SARS-CoV-2 RBD nanoparticle-induced immunogenicity and protection in mice

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; Ofer Levy

doi:10.1038/s41541-023-00610-4

Carbohydrate fatty acid monosulphate: oil-in-water adjuvant enhances SARS-CoV-2 RBD nanoparticle-induced immunogenicity and protection in mice

NPJ Vaccines. 2023 Feb 14;8(1):18. doi: 10.1038/s41541-023-00610-4.

Authors

Etsuro Nanishi^#^{1

2}, Francesco Borriello^#^{1

2

3

4}, Hyuk-Soo Seo^{5

6}, Timothy R O'Meara¹, Marisa E McGrath⁷, Yoshine Saito¹, Jing Chen⁸, Joann Diray-Arce^{1

2}, Kijun Song⁵, Andrew Z Xu⁵, Soumik Barman^{1

2}, Manisha Menon¹, Danica Dong¹, Timothy M Caradonna⁹, Jared Feldman⁹, Blake M Hauser⁹, Aaron G Schmidt^{9

10}, Lindsey R Baden¹¹, Robert K Ernst¹², Carly Dillen⁷, Jingyou Yu¹³, Aiquan Chang¹³, Luuk Hilgers¹⁴, Peter Paul Platenburg¹⁴, Sirano Dhe-Paganon^{5

6}, Dan H Barouch¹³, Al Ozonoff^{1

2

15}, Ivan Zanoni^{2

3}, Matthew B Frieman⁷, David J Dowling^{1

2}, Ofer Levy^{16

17

18}

Affiliations

¹ Precision Vaccines Program, Boston Children's Hospital, Boston, MA, USA.
² Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
³ Division of Immunology, Boston Children's Hospital, Boston, MA, USA.
⁴ Generate Biomedicines, Cambridge, MA, USA.
⁵ Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁶ Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
⁷ Department of Microbiology and Immunology, Center for Pathogen Research, University of Maryland School of Medicine, Baltimore, MD, USA.
⁸ Research Computing Group, Boston Children's Hospital, Boston, MA, USA.
⁹ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
¹⁰ Department of Microbiology, Harvard Medical School, Boston, MA, USA.
¹¹ Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹² Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD, USA.
¹³ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
¹⁴ LiteVax B.V, Oss, The Netherlands.
¹⁵ Broad Institute of MIT & Harvard, Cambridge, MA, USA.
¹⁶ Precision Vaccines Program, Boston Children's Hospital, Boston, MA, USA. ofer.levy@childrens.harvard.edu.
¹⁷ Department of Pediatrics, Harvard Medical School, Boston, MA, USA. ofer.levy@childrens.harvard.edu.
¹⁸ Broad Institute of MIT & Harvard, Cambridge, MA, USA. ofer.levy@childrens.harvard.edu.

^# Contributed equally.

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.

Abstract

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