Nanoparticles / Papillomavirus Infections / Disease Models, Animal · Journal article
Human Vaccines & Immunotherapeutics · June 16, 2026
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This preclinical murine study reports that HPV16 E7 mRNA/LNP vaccine achieved tumor regression, undetectable HPV16 E6/E7 DNA, and durable immune memory in both therapeutic (initiated 3 days post-implantation) and preventive (pre-implantation) settings using low tumor burden (5,000–10,000 TC-1 cells). E7 vaccination outperformed E6 across regimens. No human efficacy, clinical comparators, or long-term safety data are provided.
Preclinical murine tumor model study with preventive and therapeutic arms. Female mice (strain not specified) implanted with HPV16-positive TC-1 tumor cells at low inoculum (5,000–10,000 cells) to model early-intervention HPV disease. Intervention: HPV16 E7 mRNA/LNP vaccine, administered intramuscularly at 1 µg (low-dose, single), 10 µg (single therapeutic dose), or 10 µg + 5 µg (two-dose therapeutic regimen), or two 5 µg doses (preventive regimen). Compared with: HPV16 E6 mRNA/LNP vaccine; E7 versus E6 compared within study; NSS (normal saline solution) control mentioned in graphical abstract. Center of Excellence in Vaccine Research and Development, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
E7 mRNA/LNP induced stronger antigen-specific T cell responses than E6 at 1 µg intramuscular dose Therapeutic E7 vaccination (10 µg single or 10 µg + 5 µg two-dose) elicited robust T cell responses, significant tumor regression, and undetectable HPV16 E6/E7 DNA Preventive E7 vaccination (two 5 µg doses) prevented tumor establishment following TC-1 cell inoculation
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This preclinical finding supports further development of HPV16 E7 mRNA/LNP as a therapeutic vaccine candidate for HPV-associated disease, particularly in early-stage disease with low tumor burden. Clinical trials are needed to establish human efficacy, safety, and optimal dosing.
Preclinical murine tumor model study demonstrating HPV16 E7 mRNA/LNP vaccine efficacy in early-intervention setting, with no human data or comparator arm against standard therapy.
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This preclinical finding supports further development of HPV16 E7 mRNA/LNP as a therapeutic vaccine candidate for HPV-associated disease, particularly in early-stage disease with low tumor burden. Clinical trials are needed to establish human efficacy, safety, and optimal dosing.
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Persistent infection with high-risk human papillomavirus (HPV) drives the development of cervical and other anogenital cancers, with limited therapeutic options for early-stage disease and precancerous lesions. There is a critical unmet need for effective therapeutic vaccines capable of inducing durable immune responses to eliminate early tumor cells and prevent disease progression. In this study, we developed lipid nanoparticle (LNP)-formulated mRNA vaccines encoding HPV16 E6 and E7 oncoproteins and evaluated their efficacy in a murine model using a low tumor inoculum (5,000-10,000 TC-1 cells) to represent a low tumor burden, early-intervention setting. E7 mRNA/LNP induced stronger antigen-specific T cell responses than E6 when administered intramuscularly at a low dose (1 µg). In therapeutic settings, initiated 3 d after tumor implantation, either as a single 10 µg dose or a two-dose regimen (10 µg followed by 5 µg, 6 d apart), E7 vaccination elicited robust T cell responses, significant tumor regression, and undetectable HPV16 E6/E7 DNA, outperforming E6 across regimens. In the preventive setting, administration of two 5 µg doses of HPV16 E7 prevented tumor establishment following TC-1 cell inoculation. Importantly, E7 vaccination induced durable immune memory, as demonstrated by sustained tumor protection and undetectable HPV E6/E7 DNA upon rechallenge at 5 months. These findings highlight the potential of HPV16 E7 mRNA/LNP as a therapeutic vaccine targeting low tumor burden HPV-associated disease and support further clinical development. A multivalent mRNA vaccine targeting multiple high-risk HPV genotypes is currently under development.
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