期刊
JOURNAL OF IMMUNOLOGY
卷 206, 期 5, 页码 987-998出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.2000355
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类别
资金
- National Health and Medical Research Council Early Career Fellowship [APP1124265]
- University of Queensland Early Career Research Grant
- Foundation Research Excellence Award
- Jinggang Medicine [2017003021]
This study demonstrates the development of a nanomaterial-based therapeutic HPV vaccine that activates the inflammatory signaling pathway and promotes immune cell recruitment and dendritic cell maturation, leading to strong E7-specific CD8(+) T cell responses in mice. The vaccine shows potential for remission of established HPV-associated tumors and showcases a simple and general strategy for therapeutic HPV and other cancer vaccines.
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.
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