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Peer-reviewedCC BY 4.0Advanced Science

Sustained Delivery of a Shingles Subunit Vaccine Overcomes Age‐Related Declines in Humoral and Cellular Immunity Relative to Shingrix

  • Ye Eun Song1
  • Jerry Yan2
  • Ben S. Ou2
  • Olivia M. Saouaf1
  • Noah Eckman3
  • E. A. Appel1,2,4,5,6
6 affiliations
  1. 1Department of Materials Science & Engineering Stanford University Stanford California USA
  2. 2Department of Bioengineering Stanford University Stanford California USA
  3. 3Department of Chemical Engineering Stanford University Stanford California USA
  4. 4ChEM‐H Institute Stanford University Stanford California USA
  5. 5Woods Institute For the Environment Stanford University Stanford California USA
  6. 6Department of Pediatrics – Endocrinology Stanford University School of Medicine Stanford California USA
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Abstract

The global aging population faces heightened vulnerability to infectious diseases due to immunosenescence, which diminishes the potency, durability, and breadth of vaccine‐induced immunity. While the leading shingles vaccine, Shingrix, provides protection against herpes zoster virus for adults aged 50 and older, it is often associated with severe local and systemic reactogenicity, which limits vaccine compliance. Here, we report an injectable polymer‐nanoparticle (PNP) hydrogel platform for the sustained delivery of a shingles subunit vaccine to enhance immune responses while mitigating reactogenicity in aged mice. Hydrogel‐based vaccination elicited significantly more potent and durable humoral immune responses than Shingrix, while inflammatory cytokine levels remained below the limit of detection. Moreover, aged mice vaccinated with the hydrogel‐based vaccine exhibited robust antigen‐specific cellular immune responses. These findings demonstrate that controlling the temporal presentation of vaccine components can overcome age‐associated declines in immune responsiveness without inducing excessive inflammatory signaling. By decoupling immunogenicity from reactogenicity, our hydrogel‐based delivery strategy offers a promising approach to improve both the efficacy and tolerability of subunit vaccines for the elderly and may be broadly applicable to other vaccines targeting aging populations.

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Cite

BibTeXRIS
BibTeX
@article{song2026sustained,
  title = {{Sustained Delivery of a Shingles Subunit Vaccine Overcomes Age‐Related Declines in Humoral and Cellular Immunity Relative to Shingrix}},
  author = {Ye Eun Song and Jerry Yan and Ben S. Ou and Olivia M. Saouaf and Noah Eckman and E. A. Appel},
  journal = {Advanced Science},
  year = {2026},
  month = jul,
  doi = {10.1002/advs.76481},
  url = {https://doi.org/10.1002/advs.76481},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Sustained Delivery of a Shingles Subunit Vaccine Overcomes Age‐Related Declines in Humoral and Cellular Immunity Relative to Shingrix
AU  - Ye Eun Song
AU  - Jerry Yan
AU  - Ben S. Ou
AU  - Olivia M. Saouaf
AU  - Noah Eckman
AU  - E. A. Appel
PY  - 2026
DA  - 2026/07/13
JO  - Advanced Science
DO  - 10.1002/advs.76481
UR  - https://doi.org/10.1002/advs.76481
AB  - The global aging population faces heightened vulnerability to infectious diseases due to immunosenescence, which diminishes the potency, durability, and breadth of vaccine‐induced immunity. While the leading shingles vaccine, Shingrix, provides protection against herpes zoster virus for adults aged 50 and older, it is often associated with severe local and systemic reactogenicity, which limits vaccine compliance. Here, we report an injectable polymer‐nanoparticle (PNP) hydrogel platform for the sustained delivery of a shingles subunit vaccine to enhance immune responses while mitigating reactogenicity in aged mice. Hydrogel‐based vaccination elicited significantly more potent and durable humoral immune responses than Shingrix, while inflammatory cytokine levels remained below the limit of detection. Moreover, aged mice vaccinated with the hydrogel‐based vaccine exhibited robust antigen‐specific cellular immune responses. These findings demonstrate that controlling the temporal presentation of vaccine components can overcome age‐associated declines in immune responsiveness without inducing excessive inflammatory signaling. By decoupling immunogenicity from reactogenicity, our hydrogel‐based delivery strategy offers a promising approach to improve both the efficacy and tolerability of subunit vaccines for the elderly and may be broadly applicable to other vaccines targeting aging populations.
SN  - 2198-3844
ER  -