Comparison of replicating and nonreplicating vaccines against SARS-CoV-2

Haley E. Mudrick, Shane Massey, Erin B. McGlinch, Brian J. Parrett, Jack R. Hemsath, Mary E. Barry, Jeffrey D. Rubin, Chisom Uzendu, Michael J. Hansen, Courtney L. Erskine, Virginia P. Van Keulen, Aleksandra Drelich, Joseph A. Panos, Madiha Fida, Gina A. Suh, Tobias Peikert, Matthew S. Block, Chien Te Kent Tseng, Gloria R. Olivier, Michael A. Barry

Research output: Contribution to journalArticlepeer-review


Most gene-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are nonreplicating vectors. They deliver the gene or messenger RNA to the cell to express the spike protein but do not replicate to amplify antigen production. This study tested the utility of replication in a vaccine by comparing replication-defective adenovirus (RD-Ad) and replicating single-cycle adenovirus (SC-Ad) vaccines that express the SARS-CoV-2 spike protein. SC-Ad produced 100 times more spike protein than RD-Ad and generated significantly higher antibodies against the spike protein than RD-Ad after single immunization of Ad-permissive hamsters. SC-Ad-generated antibodies climbed over 14 weeks after single immunization and persisted for more than 10 months. When the hamsters were challenged 10.5 months after single immunization, a single intranasal or intramuscular immunization with SC-Ad-Spike reduced SARS-CoV-2 viral loads and damage in the lungs and preserved body weight better than vaccination with RD-Ad-Spike. This demonstrates the utility of harnessing replication in vaccines to amplify protection against infectious diseases.

Original languageEnglish (US)
Article numbereabm8563
JournalScience Advances
Issue number34
StatePublished - Aug 2022

ASJC Scopus subject areas

  • General


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