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do the rAd5 therapeutic vaccines work in this study?","Question",{"text":63,"@type":64},"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.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What tumor model and treatment route were used?",{"text":68,"@type":64},"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.",{"name":70,"@type":61,"acceptedAnswer":71},"What outcomes were observed with rAd5-16/E6E7Wt?",{"text":72,"@type":64},"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 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Vaccination in a Pre-Clinical Murine Study  \nMolly 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  \nCitation: 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  \nPre-Clinical Murine Study. Vaccines 2024, 12, 955. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/vaccines12090955](10.3390/vaccines12090955)  \nAcademic Editors: Yufeng Yao and Li Shi  \nReceived: 2 July 2024  \nRevised: 7 August 2024  \nAccepted: 13 August 2024  \nPublished: 23 August 2024  \nCopyright: © 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/)) .  \n1 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.)  \n2 School of Biochemistry and Cell Biology, University College Cork, T12 XF62 Cork, Ireland  \n3 National Institute of Bioprocessing Research and Training, A94 X099 Dublin, Ireland  \n* [Correspondence: mbraun@vaxart.com](Correspondence: mbraun@vaxart.com)  \nAbstract: 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.  \nKeywords: human papillomavirus; therapeutic vaccination; mucosal immunity; CD8+ T cell responses  \n1. Introduction  \nMost 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","cbCaibcg5AK0Wql1","https://ap.wps.com/l/cbCaibcg5AK0Wql1","pdf",1673118,15,"English","# Abstract\n# Introduction","[{\"question\":\"How do the rAd5 therapeutic vaccines work in this study?\",\"answer\":\"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.\"},{\"question\":\"What tumor model and treatment route were used?\",\"answer\":\"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.\"},{\"question\":\"What outcomes were observed with rAd5-16/E6E7Wt?\",\"answer\":\"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.\"}]","Elimination of Human Papillomavirus 16-Positive Tumors by a Mucosal rAd5 Therapeutic Vaccination in a Pre-Clinical Murine Study | PDF",1789998571,38]