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

Kelesidis, Theodoros; Kendall, Michelle A; Danoff, Ann et al. (2018) Soluble levels of receptor for advanced glycation endproducts and dysfunctional high-density lipoprotein in persons infected with human immunodeficiency virus: ACTG NWCS332. Medicine (Baltimore) 97:e10955
Kearney, Mary F; Spindler, Jonathan; Wiegand, Ann et al. (2018) Lower pre-ART intra-participant HIV-1 pol diversity may not be associated with virologic failure in adults. PLoS One 13:e0190438
Hong, Feiyu; Jacobs, Jana L; Aga, Evgenia et al. (2018) Associations between HIV-1 DNA copy number, proviral transcriptional activity, and plasma viremia in individuals off or on suppressive antiretroviral therapy. Virology 521:51-57
Akpa, Onoja; Miyahara, Sachiko; Taiwo, Babafemi et al. (2018) Similar changes in neuropsychological functioning in english and spanish speaking HIV patients. Brain Behav 8:e01083
Wyles, David L; Kang, Minhee; Matining, Roy M et al. (2018) Similar Low Rates of HCV Recurrence in HCV/HIV- and HCV-Infected Participants who Achieved SVR After DAA Treatment: Interim Results From the ACTG A5320 Viral Hepatitis C Infection Long-term Cohort Study (V-HICS). Open Forum Infect Dis 5:ofy103
Wilkin, Timothy J; Chen, Huichao; Cespedes, Michelle S et al. (2018) A Randomized, Placebo-Controlled Trial of the Quadrivalent Human Papillomavirus Vaccine in Human Immunodeficiency Virus-Infected Adults Aged 27 Years or Older: AIDS Clinical Trials Group Protocol A5298. Clin Infect Dis 67:1339-1346
Cranston, Ross D; Cespedes, Michelle S; Paczuski, Pawel et al. (2018) High Baseline Anal Human Papillomavirus and Abnormal Anal Cytology in a Phase 3 Trial of the Quadrivalent Human Papillomavirus Vaccine in Human Immunodeficiency Virus-Infected Individuals Older Than 26 Years: ACTG 5298. Sex Transm Dis 45:266-271
Benson, Constance A; Andersen, Janet W; Macatangay, Bernard J C et al. (2018) Safety and Immunogenicity of Zoster Vaccine Live in Human Immunodeficiency Virus-Infected Adults With CD4+ Cell Counts >200 Cells/mL Virologically Suppressed on Antiretroviral Therapy. Clin Infect Dis 67:1712-1719
Dompreh, Albert; Tang, Xiaoli; Zhou, Jianlin et al. (2018) Effect of Genetic Variation of NAT2 on Isoniazid and SLCO1B1 and CES2 on Rifampin Pharmacokinetics in Ghanaian Children with Tuberculosis. Antimicrob Agents Chemother 62:
Stringer, Elizabeth M; Kendall, Michelle A; Lockman, Shahin et al. (2018) Pregnancy outcomes among HIV-infected women who conceived on antiretroviral therapy. PLoS One 13:e0199555

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