A single subcutaneous or intranasal immunization with adenovirus-based SARS-CoV-2 vaccine induces robust humoral and cellular immune responses in mice

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, Andrea Gambotto*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

24 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1774-1784
Number of pages11
JournalEuropean Journal of Immunology
Issue number7
Publication statusPublished - Jul 2021

Bibliographical note

Funding Information:
AG is funded by NIH Grants (UM1‐AI106701, R21‐AI130180, U01‐CA233085) and UPMC Enterprises IPA 25565. LDF is funded by NIH Grants (UM1‐AI106701, R01‐AR074285, R01‐AR071277) and UPMC Enterprises IPA 25565. MJS is funded by NIH Grants (R01‐AI137132 and R01‐AI43603). AG, LDF, and MJS acknowledge the support from the University of Pittsburgh Clinical and Translational Science Institute (CTSI) and the DSF Charitable Foundation. These funding institutions had no role in the study design, data collection, data analysis, and interpretation of this publication. The authors acknowledge BioRender for the preparation of the Graphical Abstract.

Publisher Copyright:
© 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH


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