npj Vaccines (Feb 2023)

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
https://doi.org/10.1038/s41541-023-00610-4
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 16

Abstract

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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.