Preventive and therapeutic efficacy of mRNA/LNP vaccines encoding HPV16 E6 and E7 in an early-intervention HPV tumor mouse models.

Authors

Supichcha Saithong, Eakachai Prompetchara, Chutitorn Ketloy, Chirayus Khawsang, Kittipan Tharakhet, Papatsara Kaewpang, Nongnaphat Yostrerat, Pachara Wangsoontorn, Kunlanan Charsangbong, Kieu Lam, James Heyes, Drew Weissman, Kiat Ruxrungtham

Published in

Human vaccines & immunotherapeutics. Volume 22. Issue 1. Pages 2686510. Epub Jun 16, 2026.

Abstract

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.

PMID:
42301768
Bibliographic data and abstract were imported from PubMed on 17 Jun 2026.

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