Sustained exposure to multivalent antigen-decorated nanoparticles generates broad anti-coronavirus responses

Julie Baillet^{1

2

3}, John H Klich^{4

3}, Ben S Ou⁴, Emily L Meany⁴, Jerry Yan⁴, Theodora U J Bruun^{5

6}, Ashley Utz^{7

8}, Carolyn K Jons¹, Sebastien Lecommandoux², Eric A Appel^{1

4

5

9

10

11

12}

Affiliations

¹ Department of Material Science and Engineering, Stanford University, Stanford, CA, 94305, USA.
² Univ. Bordeaux, CNRS, Bordeaux INP, LCPO, UMR 5629, F-33600 Pessac, France.
³ These authors contributed equally.
⁴ Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
⁵ Sarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA.
⁶ Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, 94305, USA.
⁷ Stanford Biophysics Program, Stanford University School of Medicine, Stanford, CA, 94305, USA.
⁸ Stanford Medical Scientist Training Program, Stanford University School of Medicine, Stanford, CA, 94305, USA.
⁹ Institute for Immunity, Transplantation, & Infection, Stanford University School of Medicine, Stanford, CA, 94305, USA.
¹⁰ Department of Pediatrics-Endocrinology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
¹¹ Wood Institute for the Environment, Stanford University, Stanford CA, 94305, USA.
¹² Lead contact.

PMID: 40821443
PMCID: PMC12352413 (available on 2026-02-25)
DOI: 10.1016/j.matt.2025.102006

Sustained exposure to multivalent antigen-decorated nanoparticles generates broad anti-coronavirus responses

Julie Baillet et al. Matter. 2025.

. 2025 Apr 2;8(4):102006.

doi: 10.1016/j.matt.2025.102006. Epub 2025 Feb 25.

Authors

Affiliations

¹ Department of Material Science and Engineering, Stanford University, Stanford, CA, 94305, USA.
² Univ. Bordeaux, CNRS, Bordeaux INP, LCPO, UMR 5629, F-33600 Pessac, France.
³ These authors contributed equally.
⁴ Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
⁵ Sarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA.
⁶ Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, 94305, USA.
⁷ Stanford Biophysics Program, Stanford University School of Medicine, Stanford, CA, 94305, USA.
⁸ Stanford Medical Scientist Training Program, Stanford University School of Medicine, Stanford, CA, 94305, USA.
⁹ Institute for Immunity, Transplantation, & Infection, Stanford University School of Medicine, Stanford, CA, 94305, USA.
¹⁰ Department of Pediatrics-Endocrinology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
¹¹ Wood Institute for the Environment, Stanford University, Stanford CA, 94305, USA.
¹² Lead contact.

PMID: 40821443
PMCID: PMC12352413 (available on 2026-02-25)
DOI: 10.1016/j.matt.2025.102006

Abstract

The threat of future coronavirus pandemics requires developing effective vaccine technologies that provide broad and long-lasting protection against circulating and emerging strains. Here we report a multivalent liposomal hydrogel vaccine technology comprising the receptor binding domain (RBD) of up to four SARS and MERS coronavirus strains non-covalently displayed on the surface of the liposomes within the hydrogel structure. The multivalent presentation and sustained exposure of RBD antigens improved the potency, neutralizing activity, durability, and consistency of antibody responses across homologous and heterologous coronavirus strains in a naïve murine model. When administrated in animals pre-exposed to wild-type SARS-CoV-2 antigens, liposomal hydrogels elicited durable antibody responses against the homologous SARS and MERS strains for over six months and elicited neutralizing activity against the immune-evasive SARS-CoV-2 variant Omicron BA.4/BA.5. Overall, the tunable liposomal hydrogel platform we report here generates robust responses against diverse coronaviruses, supporting global efforts to respond to future viral outbreaks.

Keywords: Coronavirus; Drug Delivery; Hydrogels; Liposomes; Vaccines.

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Conflict of interest statement

Declaration of interest E.A.A. and J.H.K. are listed as inventors on a patent application describing the technology reported in this manuscript. E.A.A. is a co-founder, equity holder, and advisor of Appel Sauce Studios, which holds an exclusive license to the technology reported in this manuscript. All other authors have no interests to declare.

References

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Sustained exposure to multivalent antigen-decorated nanoparticles generates broad anti-coronavirus responses

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Sustained exposure to multivalent antigen-decorated nanoparticles generates broad anti-coronavirus responses

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