A dual-antigen self-amplifying RNA SARS-CoV-2 vaccine induces potent humoral and cellular immune responses and protects against SARS-CoV-2 variants through T cell-mediated immunity.

Autor:	McCafferty S; Ziphius Vaccines NV, B-9820 Merelbeke, Belgium; Laboratory of Gene Therapy, Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, B-9820 Merelbeke, Belgium. Electronic address: sean.mccafferty@ziphius.org., Haque AKMA; Ziphius Vaccines NV, B-9820 Merelbeke, Belgium., Vandierendonck A; Ziphius Vaccines NV, B-9820 Merelbeke, Belgium., Weidensee B; Ziphius Vaccines NV, B-9820 Merelbeke, Belgium., Plovyt M; Ziphius Vaccines NV, B-9820 Merelbeke, Belgium., Stuchlíková M; Ziphius Vaccines NV, B-9820 Merelbeke, Belgium., François N; Laboratory of Gene Therapy, Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, B-9820 Merelbeke, Belgium., Valembois S; Ziphius Vaccines NV, B-9820 Merelbeke, Belgium., Heyndrickx L; Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, B-2000 Antwerp, Belgium., Michiels J; Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, B-2000 Antwerp, Belgium., Ariën KK; Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, B-2000 Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, B-2000 Antwerp, Belgium., Vandekerckhove L; HIV Cure and Research Center, Faculty of Medicine and Health Sciences, Ghent University, B-9000 Ghent, Belgium., Abdelnabi R; University of Leuven, Department of Microbiology, Immunology, and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium., Foo CS; University of Leuven, Department of Microbiology, Immunology, and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium., Neyts J; University of Leuven, Department of Microbiology, Immunology, and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium; Global Virus Network (GVN), Baltimore, MD, USA., Sahu I; Ziphius Vaccines NV, B-9820 Merelbeke, Belgium. Electronic address: itishri.sahu@ziphius.org., Sanders NN; Laboratory of Gene Therapy, Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, B-9820 Merelbeke, Belgium; Cancer Research Institute (CRIG), Ghent University, B-9000 Ghent, Belgium.
Jazyk:	angličtina
Zdroj:	Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2022 Sep 07; Vol. 30 (9), pp. 2968-2983. Date of Electronic Publication: 2022 Apr 20.
DOI:	10.1016/j.ymthe.2022.04.014
Abstrakt:	Self-amplifying RNA vaccines may induce equivalent or more potent immune responses at lower doses compared to non-replicating mRNA vaccines via amplified antigen expression. In this paper, we demonstrate that 1 μg of an LNP-formulated dual-antigen self-amplifying RNA vaccine (ZIP1642), encoding both the S-RBD and N antigen, elicits considerably higher neutralizing antibody titers against Wuhan-like Beta B.1.351 and Delta B.1.617.2 SARS-CoV-2 variants compared to those of convalescent patients. In addition, ZIP1642 vaccination in mice expanded both S- and N-specific CD3 + CD4 + and CD3 + CD8 + T cells and caused a Th1 shifted cytokine response. We demonstrate that the induction of such dual antigen-targeted cell-mediated immune response may provide better protection against variants displaying highly mutated Spike proteins, as infectious viral loads of both Wuhan-like and Beta variants were decreased after challenge of ZIP1642 vaccinated hamsters. Supported by these results, we encourage redirecting focus toward the induction of multiple antigen-targeted cell-mediated immunity in addition to neutralizing antibody responses to bypass waning antibody responses and attenuate infectious breakthrough and disease severity of future SARS-CoV-2 variants. Competing Interests: Declaration of interest S.M., A.K.M.A.H., A.V., B.W., M.P., M.S., S.V., and I.S. are current employees of Ziphius Vaccines NV and may own Ziphius shares/warrants. S.M., A.K.M.A.H., S.V., I.S., and N.N.S. are inventors on a patent application claiming subject matter related to the SARS-CoV-2 saRNA vaccine candidates described herein. The Virology Unit of the Institute of Tropical Medicine, supervised by K.K.A., and the Department of Microbiology, Immunology, and Transplantation of Rega Institute for Medical Research (KUL), supervised by J.N., received compensation from Ziphius Vaccines NV to perform the neutralization assays and hamster studies, respectively. The authors declare no other competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu