Melamed Lab

COVID-19 Vaccines

Written by: Hector Fernandez
Edited by: Jina Zhou and Esther Melamed
9/3/2020

Currently there is a large number of vaccine candidates in the R&D landscape for coronavirus prevention. As of July 20, 2020, there are more than a hundred candidates seeking to reach the market with twenty-three of them approved for clinical trials (with other developers making plans to start trials later this year), according to the World Health Organization.  The majority of vaccine platforms intend to stimulate the production of antibodies against the viral spike (S) protein which is essential for uptake of the virus by epithelial cells via the human ACE2 receptor. The following article will provide an overview of the different types of vaccines currently in development as well as a brief summary of the more prominent vaccine candidates undergoing clinical trials. 

Types of COVID-19 Vaccine Candidates

The ongoing pandemic has spurred an explosion of candidate vaccines attempting to reach the market and gain approval for the first official COVID-19 vaccine. These range from more traditional vaccines, such as whole-pathogen vaccines, to more modern “new generation” technologies which incorporate a specific antigen or antigens from the virus. Table 1 gives an overview of the different vaccine types currently being considered for development.

Table 1 – Vaccine type overview.

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Vaccine Delivery Systems in the Era of COVID-19

One of the noteworthy aspects of this race is the wide variety of technologies being developed to deliver the viral particle mimic (i.e. either the full S protein or the receptor binding domain (RBD) of the S protein) used to produce an effective immune response in the host. These range from previously used technologies, such as viral vector vaccines formerly developed for SARS-CoV, as well as more recently studied systems like the mRNA vaccines. Table 2 gives a brief overview of the current COVID-19 vaccine delivery system landscape.

Table 2 – Overview of COVID-19 vaccine delivery systems.

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Vaccine Clinical Trials 

The following table provides an overview of some of the top contender vaccine candidates under clinical development (for a comprehensive list please visit: https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines ). 

Table 3 – Summary of vaccine candidates currently in clinical trials.

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mRNA-1273

  • mRNA vaccine that encodes for a prefusion stabilized form of the Spike (S) protein (allows virus into cells)
  • Phase I, open-label, trial enrolling 45 healthy adult volunteers ages 18 to 55 years over approximately 6 weeks.
    • Start Date: March 16, 2020.
    • Estimated study completion date: Pending
  • Developed by Moderna, Inc.
  • Moderna published Phase I results on July 14, 2020.  

INO-4800

  • DNA vaccine (optimized DNA plasmid) which utilizes the CELLECTRA® electroporation platform to deliver the plasmid into cells.  
  • Phase I, open-label, trial enrolling 40 healthy participants ages 18 to 50 years.
    • Start date- April 3, 2020
    • Estimated study completion date – November 2020
  • Developed by Inovio Pharmaceuticals 

Ad5-nCoV

  • First vaccine for COVID-19 in a Phase 1 Clinical Trial in China
  • Uses CanSinoBIO’s adenovirus-based viral vector vaccine technology platform to express SARS-CoV-2 spike protein
  • Phase I, open-label, trial enrolling 180 healthy participants ages 18 to 60 years.
    • Start date: March 16, 2020
    • Estimated study completion date: December 20, 2022
  • Developed by CanSino Biologics Inc. 

LV-SMENP-DC

  • Vaccine exploits COVID-19 engineered minigenes, which are delivered via a lentiviral vector system (NHP/TYF), to express viral proteins and immune modulatory genes. This technology hopes to modify dendritic cells (DCs) and therefore activate T cells to fight the virus.
  • Phase I, open-label, trial enrolling 100 Laboratory (RT-PCR) confirmed Covid-19 infection participants ages 6 months to 80 years.
    • Start date: March 24, 2020
    • Estimated study completion date: December 31, 2024
  • Developed by Shenzhen Geno-Immune Medical Institute 

Covid-19 aAPC Vaccine

  • This vaccine works by applying a lentiviral vector system (NHP/TYF), which contains immune modulatory genes and viral minigenes, to artificial antigen presenting cells (aAPCs). The Covid-19/aAPCs are then inactivated for proliferation and subcutaneous injected at 0, 14 and 28 days (each injection approximately containing 5×106 cells).
  • Phase I, open-label, trial enrolling 100 healthy and Covid-19-positive participants ages 6 months to 80 years.
    • Start date: February 15, 2020
    • Estimated study completion date: December 31, 2024
  • Developed by Shenzhen Geno-Immune Medical Institute 

ChAdOx1

  • Originally developed to target MERS, ChAdOx1 uses an attenuated adenovirus viral vector (which commonly causes infections in chimpanzees) that is engineered to produce the spike (S) protein of SARS-CoV-2
  • Phase I/II single-blinded, randomized study enrolling 1112 healthy participants aged 18-55 years. 
    • Start date: April 23, 2020
    • Estimated study completion date: May 2021
  • Developed by the University of Oxford. 

BNT162

  • mRNA-based coronavirus vaccine encapsulated in Lipid Nanoparticles (LNPs).
  • Phase I/II multi-site, 2-part, dose-escalation trial enrolling 196 healthy adult participants aged 18-55
    • Start date: April 20, 2020
    • Trials started in US on May 4, 2020
  • Developed by BioNTech and Pfizer

CoronaVac

  • Purified, inactivated, SARS-CoV-2 virus vaccine. This candidate showed a robust production of SARS-CoV-2-specific neutralizing antibodies in animal studies. 
  • Phase I/II randomized, double-blinded, single-center, placebo-controlled clinical trial enrolling 744 (44 at phase I, 600 at phase II) healthy adults aged 18-59 years
    • Start date: April 16, 2020
    • Estimated study completion date: December 13, 2020
  • Developed by Sinovac Research & Development Co., Ltd.
  • The Sinovac, in conjunction with the Brazilian biotech company Butantan, were granted approval for a Phase III trial in July 3, 2020.
References
  1. The COVID-19 vaccine development landscape. (2020, April 9). Nature. https://www.nature.com/articles/d41573-020-00073-5
  2. Wang J, Peng Y, Xu H, Cui Z, Williams RO 3rd. The COVID-19 Vaccine Race: Challenges and Opportunities in Vaccine Formulation. AAPS PharmSciTech. 2020;21(6):225. Published 2020 Aug 5. doi:10.1208/s12249-020-01744-7
  3. Safety and immunogenicity study of 2019-nCoV vaccine (mrna-1273) for prophylaxis SARS Cov-2 infection. (n.d.). Home – ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04283461
  4. A phase I clinical trial in 18-60 adults – Full text view – ClinicalTrials.gov. (n.d.). Home – ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04313127
  5. Safety, tolerability and immunogenicity of INO-4800 for COVID-19 in healthy volunteers. (n.d.). Home – ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/record/NCT04336410
  6. Immunity and safety of COVID-19 synthetic Minigene vaccine. (n.d.). Home – ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04276896
  7. Safety and immunity of COVID-19 aAPC vaccine. (n.d.). Home – ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04299724
  8. A study of a candidate COVID-19 vaccine (COV001) – Full text view – ClinicalTrials.gov. (n.d.). Home – ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04324606?term=vaccine&cond=covid-19&draw=2
  9. Clinical trials register. (n.d.). EU Clinical Trials Register – Update. https://www.clinicaltrialsregister.eu/ctr-search/search?query=BNT162-01
  10. Safety and immunogenicity study of inactivated vaccine for prophylaxis of SARS Cov-2 infection (COVID-19). (n.d.). Home – ClinicalTrials.gov.https://clinicaltrials.gov/ct2/show/NCT04352608?term=Sinovac&cntry=CN&draw=2
  11. Draft landscape of COVID 19 candidate vaccines. (n.d.). WHO | World Health Organization. https://www.who.int/who-documents-detail/draft-landscape-of-covid-19-candidate-vaccines