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

Author:

Mudrick Haley E.1ORCID,Massey Shane2ORCID,McGlinch Erin B.34ORCID,Parrett Brian J.34,Hemsath Jack R.35ORCID,Barry Mary E.5,Rubin Jeffrey D.4ORCID,Uzendu Chisom4,Hansen Michael J.6,Erskine Courtney L.6ORCID,Van Keulen Virginia P.6ORCID,Drelich Aleksandra7,Panos Joseph A.8ORCID,Fida Madiha5ORCID,Suh Gina A.5ORCID,Peikert Tobias6910,Block Matthew S.69ORCID,Tseng Chien-Te Kent2711ORCID,Olivier Gloria R.12ORCID,Barry Michael A.5613ORCID

Affiliation:

1. Molecular Pharmacology and Experimental Therapeutics (MPET) Graduate Program, Mayo Clinic, Rochester, MN, USA.

2. Center of Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, TX, USA.

3. Graduate Research Education Program (GREP), Mayo Clinic, Rochester, MN, USA.

4. Virology and Gene Therapy (VGT) Graduate Program, Mayo Clinic, Rochester, MN, USA.

5. Department of Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN, USA.

6. Department of Immunology, Mayo Clinic, Rochester, MN, USA.

7. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.

8. Rehabilitation Medicine Research Center, Musculoskeletal Gene Therapy Research Laboratory, Mayo Clinic Medical Scientist Training Program, Mayo Clinic, Rochester, MN, USA.

9. Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA.

10. Department of Medicine, Division of Pulmonary Care, Mayo Clinic, Rochester, MN, USA.

11. Institutional Office of Regulated Nonclinical Studies, University of Texas Medical Branch, Galveston, TX, USA.

12. Mayo Clinic Ventures, Mayo Clinic, Rochester, MN, USA.

13. Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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