Abstract

The novel SARS-CoV-2 is the cause of the coronavirus (CoV) disease (COVID-19) outbreak that currently pose a serious pandemic threat to public health. A safe vaccine that rapidly induces long-lasting virus-specific immune responses is urgently needed. The CoV spike (S) protein, a characteristic structural component of the viral envelope, is considered a key target for vaccines against CoV infection, as we and others have previously demonstrated for severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS) CoV infections. The safety profile of non-infectious recombinant protein subunit vaccines makes them suitable for SARS-CoV-2 vaccine candidates for preclinical testing. To develop a SARS-CoV-2 vaccine, we constructed SARS-CoV-2-S1 subunit constructs and established an intracutaneous delivery platform using a novel, dissolving microneedle array (MNA) that enhances the immunogenicity of these subunit vaccines in mice, as determined by S1 specific viral titers in serum. Here, we propose to evaluate this PittCoVacc vaccine in a phase I clinical trial through a single specific aim designed to complete ongoing IND enabling studies, any additional parallel studies recommended by the FDA, and then to conduct a Phase 1 clinical trial in healthy volunteers.

Public Health Relevance

The novel coronavirus, previously dubbed 2019-nCoV, and now officially named SARS-CoV-2 which caused the corona virus disease (COVID-19) pandemic outbreak and was first detected in Wuhan, China in December 2019. Safe vaccines that rapidly induce long-lasting virus-specific immune responses are urgently needed. We have recently established that intracutaneous delivery using a novel, dissolving microneedle array the SARS-CoV-2 Spike 1 subunit vaccine (PittCoVacc) is immunogenic in a murine mouse model. Here, we propose to evaluate the PittCoVacc vaccine in an investigator-initiated phase I clinical trial. This research project will provide critically important information on the safety and immunogenicity of the PittCoVacc.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
3UM1AI106701-07S2
Application #
10147381
Study Section
Program Officer
Livnat, Daniella
Project Start
2020-07-15
Project End
2020-11-30
Budget Start
2020-07-15
Budget End
2020-11-30
Support Year
7
Fiscal Year
2020
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Pediatrics
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Strongin, Zachary; Sharaf, Radwa; VanBelzen, D Jake et al. (2018) Effect of Short-Term Antiretroviral Therapy Interruption on Levels of Integrated HIV DNA. J Virol 92:
Gandhi, Monica; Ofokotun, Igho; Bacchetti, Peter et al. (2018) Antiretroviral concentrations in hair strongly predict virologic response in a large HIV treatment-naive clinical trial. Clin Infect Dis :
Shivakoti, Rupak; Gupte, Nikhil; Tripathy, Srikanth et al. (2018) Inflammation and micronutrient biomarkers predict clinical HIV treatment failure and incident active TB in HIV-infected adults: a case-control study. BMC Med 16:161
Moro, Ruth N; Scott, Nigel A; Vernon, Andrew et al. (2018) Exposure to Latent Tuberculosis Treatment during Pregnancy. The PREVENT TB and the iAdhere Trials. Ann Am Thorac Soc 15:570-580
Horita, Yasuhiro; Alsultan, Abdullah; Kwara, Awewura et al. (2018) Evaluation of the Adequacy of WHO Revised Dosages of the First-Line Antituberculosis Drugs in Children with Tuberculosis Using Population Pharmacokinetic Modeling and Simulations. Antimicrob Agents Chemother 62:
Bares, Sara H; Smeaton, Laura M; Xu, Ai et al. (2018) HIV-Infected Women Gain More Weight than HIV-Infected Men Following the Initiation of Antiretroviral Therapy. J Womens Health (Larchmt) 27:1162-1169
Koay, Wei Li A; Lindsey, Jane C; Uprety, Priyanka et al. (2018) Intestinal Integrity Biomarkers in Early Antiretroviral-Treated Perinatally HIV-1-Infected Infants. J Infect Dis 218:1085-1089
Swindells, S; Gupta, A; Kim, S et al. (2018) Resource utilization for multidrug-resistant tuberculosis household contact investigations (A5300/I2003). Int J Tuberc Lung Dis 22:1016-1022
Tracy, LaRee A; Struble, Kimberly; Firnhaber, Cynthia et al. (2018) Age Differences by Sex in Antiretroviral-Naïve Participants: Pooled Analysis from Randomized Clinical Trials. J Assoc Nurses AIDS Care 29:371-382
Stone, Mars; Bainbridge, John; Sanchez, Ana M et al. (2018) Comparison of Detection Limits of Fourth- and Fifth-Generation Combination HIV Antigen-Antibody, p24 Antigen, and Viral Load Assays on Diverse HIV Isolates. J Clin Microbiol 56:

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