Elimination of Human Papillomavirus 16-Positive Tumors by a Mucosal rAd5 Therapeutic Vaccination in a Pre-Clinical Murine Study

Sep 21, 2026

Uploaded by Miles

Therapeutic vaccination leverages the body’s cellular immune system to target and destroy cancerous cells. Several therapies exist to eliminate HPV-driven lesions, yet durable cures remain challenging. The study develops mucosally delivered, recombinant non-replicating adenovirus type 5 (rAd5) vaccines encoding HPV16 E6 and E7 plus a dsRNA adjuvant, evaluating antigen-specific T-cell induction and therapeutic efficacy in a murine HPV tumor model.

LanguageEnglish

CategoryResearch & Report

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Abstract

Introduction

Article Elimination of Human Papillomavirus 16-Positive Tumors by a Mucosal rAd5 Therapeutic Vaccination in a Pre-Clinical Murine Study Molly R. Braun 1, *, Anne C. Moore 1,2,3, Jonathan D. Lindbloom 1, Katherine A. Hodgson 1, Emery G. Dora 1 and Sean N. Tucker 1 Citation: Braun, M.R.; Moore, A.C.; Lindbloom, J.D.; Hodgson, K.A.; Dora, E.G.; Tucker, S.N. Elimination of Human Papillomavirus 16-Positive Tumors by a Mucosal rAd5 Therapeutic Vaccination in a Pre-Clinical Murine Study. Vaccines 2024, 12, 955. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/vaccines12090955](10.3390/vaccines12090955) Academic Editors: Yufeng Yao and Li Shi Received: 2 July 2024 Revised: 7 August 2024 Accepted: 13 August 2024 Published: 23 August 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Vaxart Inc., 170 Harbor Way Suite 300, South San Francisco, CA 94080, USA; [anne.moore@ucc.ie](anne.moore@ucc.ie) (A.C.M.); [edora@vaxart.com](edora@vaxart.com) (E.G.D.); [stucker@vaxart.com](stucker@vaxart.com) (S.N.T.) 2 School of Biochemistry and Cell Biology, University College Cork, T12 XF62 Cork, Ireland 3 National Institute of Bioprocessing Research and Training, A94 X099 Dublin, Ireland * [Correspondence: mbraun@vaxart.com](Correspondence: mbraun@vaxart.com) Abstract: Therapeutic vaccination can harness the body’s cellular immune system to target and destroy cancerous cells. Several treatment options are available to eliminate pre-cancerous and cancerous lesions caused by human papillomaviruses (HPV), but may not result in a long-term cure. Therapeutic vaccination may offer an effective, durable, and minimally intrusive alternative. We developed mucosally delivered, recombinant, non-replicating human adenovirus type 5 (rAd5)-vectored vaccines that encode HPV16′ s oncogenic proteins E6 and E7 alongside a molecular dsRNA adjuvant. The induction of antigen-specific T cells and the therapeutic efficacy of rAd5 were evaluated in a mouse model of HPV tumorigenesis where E6E7-transformed cells, TC-1, were implanted subcutaneously in C57BL/6 mice. After tumor growth, mice were treated intranasally with rAd5 vaccines expressing the wildtype form of E6E7 (rAd5-16/E6E7Wt ) in combination with an anti-PD-1 antibody or isotype control. Animals treated with rAd5-16/E6E7Wt with and without anti-PD-1 had significant reductions in tumor volume and increased survival compared to controls. Further, animals treated with rAd5-16/E6E7Wt had increased CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) and produced a cytotoxic tumor microenvironment. In a second study, the immunogenicity of anon-transformative form of E6E7 (rAd5-16/E6E7Mu ) and a vaccine encoding predicted T cell epitopesof E6E7 (rAd5-16/E6E7epi) were evaluated. These vaccines elicited significant reductions in TC-1 tumor volume and increased survival of animals. Antigen-specific CD8+ T effector memory cells were observed in the animals treated with E6E7-encoding rAd5, but not in the rAd5-empty group. The work described here demonstrates that this mucosal vaccination can be used therapeutically toelicit specific cellular immunity and further identifies a clinical candidate with great potential for the treatment and prevention of human cervical cancer. Keywords: human papillomavirus; therapeutic vaccination; mucosal immunity; CD8+ T cell responses 1. Introduction Most cervical cancers, as well as oropharyngeal and anogenital cancers, are caused by persistent infection with human papillomavirus (HPV) [1] . There are over 200 types of HPV, with HPV16 and HPV18 being responsible for 71% of cervical cancers [2] . Prophylactic vaccines against the vir

FAQs

How do the rAd5 therapeutic vaccines work in this study?

They deliver mucosally a recombinant, non-replicating rAd5 vector encoding HPV16 E6 and E7 proteins with a molecular dsRNA adjuvant to induce antigen-specific cellular immunity.

What tumor model and treatment route were used?

The authors implanted E6E7-transformed TC-1 cells in C57BL/6 mice and treated animals intranasally with rAd5 vaccines, then assessed tumor growth and survival.

What outcomes were observed with rAd5-16/E6E7Wt?

Mice receiving rAd5-16/E6E7Wt, with or without anti-PD-1, showed significant reductions in tumor volume and increased survival versus controls, along with increased CD4+ and CD8+ tumor-infiltrating lymphocytes.

Sep 21, 2026

Uploaded by Miles