Title

480 Preliminary evaluation of a novel coronavirus vaccine (CORVax) using electroporation of plasmid DNA encoding a stabilized prefusion SARS-CoV-2 spike protein alone or with transfection of plasmid IL-12

Authors

Shawn M. Jensen, Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Providence Cancer Center and Providence Portland Medical Center, Portland, OregonFollow
Christopher Twitty
Christopher Paustian
Madelein Laws
Glenna McDonnell
Keith W Wegman, Laboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Center, Earle A. Chiles Research Institute, Providence Cancer Institute, Providence Portland Medical Center, Portland, OR, USAFollow
Tarsem Moudgil, Earle A. Chiles Research Institute, Providence Cancer InstituteFollow
Michael E Afentoulis, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Cancer Institute, 2N56 North Pavilion, 4805 NE Glisan St., Portland, OR, 97213, USA.Follow
Mia Han
Kellie Malloy Foerter
David Canton
Jack Lee
Bianca Nguyen
John Rodriguez
Kim Jaffe
Brian D. Piening, Molecular Genomics Laboratory, Providence Portland Medical Center, Portland, OR; Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Cancer Center, Portland, OR.Follow
Carlo Bifulco, Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Medical Center, Portland, ORFollow
Daniel O'Connor
Walter Urba, Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, 97213, USA.Follow
Rom Leidner, Earle A. Chiles Research Institute, Providence Cancer InstituteFollow
Traci Hilton
Hong-Ming Hu, Laboratory of Cancer Immunobiology, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR, USA.Follow
Bernard A Fox, Chiles Research Institute Providence Portland Medical CenterFollow

Document Type

Article

Publication Date

11-9-2020

Publication Title

Journal of ImmunoTherapy of Cancer

Keywords

2019-nCoV

Abstract

Background SARS-CoV-2 (CoV2) has precipitated a global pandemic and the effectiveness of standard vaccine strategies to induce potent and persistent immunity to CoV2 is in question, particularly for the elderly. This problem is not dissimilar to what we have struggled with in our quest to induce immunity to cancer antigens, where vaccine-induced anti-cancer immune responses can be weak. Here, we describe a novel vaccine approach which leverages electroporation (EP) of a plasmid encoding a prefusion stabilized CoV2 spike protein (CORVax). As IL-12 has been shown to augment the efficacy of immunotherapy in aged mice,1 we have initiated studies to evaluate if plasmid IL-12 (TAVO™) can similarly augment anti-CoV2 immune responses in young mice and have planned studies in aged animals.

Methods A prefusion stabilized CoV2 spike plasmid expression vector was constructed, a master cell bank generated and clinical-grade plasmid manufactured. C57BL/6 and BALB/c were vaccinated via intramuscular (IM) and/or intradermal (ID) injection followed immediately by EP of plasmids encoding the CoV2 spike protein with or without plasmid-encoded murine IL-12 on days 1 and 14 or 21. Mice were followed for >120 days to assess safety. Splenocytes and serum were harvested at different time points to interrogate virus-specific cellular responses as well anti-spike IgG1/IgG2 antibody titers. A surrogate viral neutralization test (sVNT) assessed serum blockade of soluble hACE2R binding to immobilized CoV2 spike.

Results Preliminary data shows that EP of CORVax alone or combined with IL-12 was safe. EP of CORVax was able to elicit anti-Spike IgG antibodies (IC50 = 1/2112), as well as IgG antibodies targeting the receptor binding domain of the Spike protein (IC50 = 1/965) approximately 40 days after the booster vaccination. In 2 of 2 experiments, CORVax combined with IL-12 significantly (P<0.0001) increased the sVNT titers at 2 months, but this benefit was lost by 3 months.

Conclusions Early preclinical data shows that EP of CORVax can induce IgG responses to CoV2 Spike and the receptor binding domain (RBD) as well as apparent viral neutralizing activity. The addition of IL-12, at least transiently, increased sVNT titer. We plan to investigate alternate vaccine boosting strategies while extending these studies into aged animals and initiate a clinical trial in the near future.

http://dx.doi.org/10.1136/jitc-2020-SITC2020.0480

Clinical Institute

Cancer

Department

Earle A. Chiles Research Institute

Department

Infectious Diseases

Department

Oncology


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