Single immunizations of self-amplifying or non-replicating mRNA-LNP vaccines control HPV-associated tumors in mice.

Autor:	Ramos da Silva J; Vaccine Development Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil.; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Bitencourt Rodrigues K; Vaccine Development Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil., Formoso Pelegrin G; Vaccine Development Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil., Silva Sales N; Vaccine Development Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil., Muramatsu H; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., de Oliveira Silva M; Vaccine Development Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil., Porchia BFMM; Vaccine Development Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil.; Laboratory of Tumor Immunology, Department of Immunology, Biomedical Sciences Institute, University of São Paulo, São Paulo, SP 05508-000, Brazil.; ImunoTera Soluções Terapêuticas Ltda., São Paulo, SP 05508-000, Brazil., Moreno ACR; Vaccine Development Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil., Aps LRMM; Vaccine Development Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil.; ImunoTera Soluções Terapêuticas Ltda., São Paulo, SP 05508-000, Brazil., Venceslau-Carvalho AA; Vaccine Development Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil., Tombácz I; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Fotoran WL; Department of Parasitology, Institute for Biomedical Sciences, University of São Paulo, SP 05508-000, Brazil., Karikó K; BioNTech SE, Mainz, 55131, Germany., Lin PJC; Acuitas Therapeutics, Vancouver, BC V6T1Z3, Canada., Tam YK; Acuitas Therapeutics, Vancouver, BC V6T1Z3, Canada., de Oliveira Diniz M; Vaccine Development Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil., Pardi N; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., de Souza Ferreira LC; Vaccine Development Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil.; Scientific Platform Pasteur USP, University of São Paulo, São Paulo, SP, 05508-020, Brazil.
Jazyk:	angličtina
Zdroj:	Science translational medicine [Sci Transl Med] 2023 Mar 08; Vol. 15 (686), pp. eabn3464. Date of Electronic Publication: 2023 Mar 08.
DOI:	10.1126/scitranslmed.abn3464
Abstrakt:	As mRNA vaccines have proved to be very successful in battling the coronavirus disease 2019 (COVID-19) pandemic, this new modality has attracted widespread interest for the development of potent vaccines against other infectious diseases and cancer. Cervical cancer caused by persistent human papillomavirus (HPV) infection is a major cause of cancer-related deaths in women, and the development of safe and effective therapeutic strategies is urgently needed. In the present study, we compared the performance of three different mRNA vaccine modalities to target tumors associated with HPV-16 infection in mice. We generated lipid nanoparticle (LNP)-encapsulated self-amplifying mRNA as well as unmodified and nucleoside-modified non-replicating mRNA vaccines encoding a chimeric protein derived from the fusion of the HPV-16 E7 oncoprotein and the herpes simplex virus type 1 glycoprotein D (gDE7). We demonstrated that single low-dose immunizations with any of the three gDE7 mRNA vaccines induced activation of E7-specific CD8 + T cells, generated memory T cell responses capable of preventing tumor relapses, and eradicated subcutaneous tumors at different growth stages. In addition, the gDE7 mRNA-LNP vaccines induced potent tumor protection in two different orthotopic mouse tumor models after administration of a single vaccine dose. Last, comparative studies demonstrated that all three gDE7 mRNA-LNP vaccines proved to be superior to gDE7 DNA and gDE7 recombinant protein vaccines. Collectively, we demonstrated the immunogenicity and therapeutic efficacy of three different mRNA vaccines in extensive comparative experiments. Our data support further evaluation of these mRNA vaccines in clinical trials.
Databáze:	MEDLINE
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