Manganese-doped silica-based nanoparticles promote the efficacy of antigen-specific immunotherapy

Janin Chandra, Siok Min Teoh, Paula Kuo, Lynn Tolley, Abate Assefa Bashaw, Zewen Kelvin Tuong, Yang Liu, Zibin Chen, James W. Wells, Chengzhong Yu, Ian H. Frazer, Meihua Yu

Research output: Journal article publicationJournal articleAcademic researchpeer-review

2 Citations (Scopus)

Abstract

Prophylactic human papillomavirus (HPV) vaccines are commercially available for prevention of infection with cancerogenic HPV genotypes but are not able to combat pre-existing HPV-associated disease. In this study, we designed a nanomaterial-based therapeutic HPV vaccine, comprising manganese (Mn4+)-doped silica nanoparticles (Mn4+-SNPs) and the viral neoantigen peptide GF001 derived from the HPV16 E7 oncoprotein. We show in mice that Mn4+-SNPs act as self-adjuvants by activating the inflammatory signaling pathway via generation of reactive oxygen species, resulting in immune cell recruitment to the immunization site and dendritic cell maturation. Mn4+-SNPs further serve as Ag carriers by facilitating endo/lysosomal escape via depletion of protons in acidic endocytic compartments and subsequent Ag delivery to the cytosol for cross-presentation. The Mn4+-SNPs+GF001 nanovaccine induced strong E7-specific CD8+ T cell responses, leading to remission of established murine HPV16 E7-expressing solid TC-1 tumors and E7-expressing transgenic skin grafts. This vaccine construct offers a simple and general strategy for therapeutic HPV and potentially other cancer vaccines.

Original languageEnglish
Pages (from-to)987-998
Number of pages12
JournalJournal of Immunology
Volume206
Issue number5
DOIs
Publication statusPublished - 1 Mar 2021
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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