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A single subcutaneous or intranasal immunization with adenovirus-based SARS-CoV-2 vaccine induces robust humoral and cellular immune responses in mice |
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| Authors: | Eun Kim Florian J. Weisel Stephen C. Balmert Muhammad S. Khan Shaohua Huang Geza Erdos Thomas W. Kenniston Cara Donahue Carey Stephen M. Joachim Laura J. Conter Nadine M. Weisel Nisreen M. A. Okba Bart L. Haagmans Elena Percivalle Irene Cassaniti Fausto Baldanti Emrullah Korkmaz Mark J. Shlomchik Louis D. Falo Jr Andrea Gambotto |
| Affiliation: | 1. Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Mark J. Shlomchik, Louis D. Falo Jr, and Andrea Gambotto are cosenior authors.;2. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Mark J. Shlomchik, Louis D. Falo Jr, and Andrea Gambotto are cosenior authors.;3. Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;4. Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA;5. Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;6. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;7. Department of Viroscience, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands;8. Molecular Virology Unit, Microbiology and Virology Department, IRCCS Policlinico San Matteo, Pavia, Italy;9. Molecular Virology Unit, Microbiology and Virology Department, IRCCS Policlinico San Matteo, Pavia, Italy Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy;10. Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, PA, USA;11. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Eun Kim and Florian J. Weisel equally contributed to this work.;12. Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, PA, USA Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA The McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA UPMC Hillman Cancer Center, Pittsburgh, PA, USA Eun Kim and Florian J. Weisel equally contributed to this work. |
| Abstract: | Optimal vaccines are needed for sustained suppression of SARS-CoV-2 and other novel coronaviruses. Here, we developed a recombinant type 5 adenovirus vector encoding the gene for the SARS-CoV-2 S1 subunit antigen (Ad5.SARS-CoV-2-S1) for COVID-19 immunization and evaluated its immunogenicity in mice. A single immunization with Ad5.SARS-CoV-2-S1 via S.C. injection or I.N delivery induced robust antibody and cellular immune responses. Vaccination elicited significant S1-specific IgG, IgG1, and IgG2a endpoint titers as early as 2 weeks, and the induced antibodies were long lasting. I.N. and S.C. administration of Ad5.SARS-CoV-2-S1 produced S1-specific GC B cells in cervical and axillary LNs, respectively. Moreover, I.N. and S.C. immunization evoked significantly greater antigen-specific T-cell responses compared to unimmunized control groups with indications that S.C. injection was more effective than I.N. delivery in eliciting cellular immune responses. Mice vaccinated by either route demonstrated significantly increased virus-specific neutralization antibodies on weeks 8 and 12 compared to control groups, as well as BM antibody forming cells (AFC), indicative of long-term immunity. Thus, this Ad5-vectored SARS-CoV-2 vaccine candidate showed promising immunogenicity following delivery to mice by S.C. and I.N. routes of administration, supporting the further development of Ad-based vaccines against COVID-19 and other infectious diseases for sustainable global immunization programs. |
| Keywords: | Adenovirus COVID-19 Infectious diseases Recombinant DNA vaccines SARS-CoV-2 |