COVID-19, Prevention

by Editorial Board last updated 2020-12-02 08:19:34.138996-05:00
Vaccine Development Pipeline

Introduction

  • Genetic structure of SARS-CoV-2 released on 11 Jan 2020
  • Several vaccine candidates (anti-spike; "S" protein) created within 2 days of release of the structure
  • At least 115 vaccine candidates have been developed; 78 are confirmed and active.
  • Types of vaccine products include:  
    • RNA
    • DNA
    • Virus-like particles (VLPs)
    • Peptides
    • Viral vectors (replicating and non-replicating)
    • Recombinant Proteins
    • Live attenuated viruses
    • Inactivated viruses
  • RNA and DNA vaccines have the greatest ability for rapid, large-scale manufacturing (scale-up) and greater flexibility for antigen manipulation.  Viral vectors have a large level of protein expression, stability, and strong immune responses. Recombinant protein technology is widely used for many existing diseases, so lots of experience and existing production capacity.
  • Both Pfizer/ BioNTech and Moderna mRNA vaccines demonstrate 95% efficacy in Phase III trials (Nov 2020); both companies filing for Early Use Authorization approval by US FDA.  Vaccines should begin to be available by Jan 2021, peak distribution by 2nd Q 2021

Vaccine Development Pipeline

  • Currently in Clinical Trials
Class / Platform / Type of Candidate

Development
Phase

Maker Comments

LIPID NANOPARTICLE (LNP) - encapsulated mRNA

    Encodes for the "S" Protein. Preliminary report of two-dose regimens in a dose-escalation study of 45 adults age 18-55; high titers of specific neutralizing antibodies in a dose response with CD4 T-cell response also present; acceptable safety profile

Moderna

mRNA-1273

Phase 3 enrollment announced 27 Jul 2020 (30,000 participants at 89 U.S. sites)
NCT04470427
NCT04283461

Moderna / NIAID

 (N Engl J Med online 14 Jul 2020, DOI: 10.1056/NEJMoa2022483)

Announcement Phase III study demonstrates 95% efficacy

Company will file for EUA with FDA

Pfizer 

BNT162b1

Phase 3

NCT04368728

BioNTech

Expresses 'S' Protein Trimer

Strong neutralizing antibody responses in Phase I study

Announcement Phase III study demonstrates 95% efficacy

EUA granted in UK (2 Dec 2020). Company will file for EUA with FDA

AnGes; Osaka University

ARCoV

Phase 2/3

NCT04527081

 Takara Bio  Cell Volume 182, Issue 5, 3 September 2020, Pages 1271-1283.e16

Arcturus Therapeutics; Duke-NUS

ARCT-021

 Phase 2

NCT04480957

Arcturus Therapeutics  

VIRAL VECTOR VACCINE

     

Chimpanzee adenovirus vectored

ChAdOx1 nCov-19

Phase 3 ( clinical hold lifted on 14 Sept 2020)

Was placed due to a case of Transverse myelitis; 8 Sept 2020

NCT04516746 (USA)

NCT04444674 (S. Africa)

Oxford / Astra Zeneca Expresses "S" protein of SARS CoV-2. Single blind RCT (1077 participants) meningococcal vaccine as control; specific antibody and T-cell observed with prime-boost regimen; acceptable safety profile reported)(Lancet online 20 Jul 2020)

Adenovirus Type 5 

Ad5-nCoV

Phase 3

ChiCTR2000031781

NCT04526990

CanSino Biological Inc./Beijing Institute of Biotechnology

Replication deficient Viral Vector. Expresses "S" Protein. Phase 2 double blind, placebo controlled RCT (603 participants) of two  single dose regimens (1 × 1011 viral particles per mL or 5 × 1010 viral particles per mL) vs placebo reported safe with significant immune responses both anitbody and cell-mediated (Lancet online 20 Jul 2020)

Adenovirus

Ad26.COV2.S

Phase 3

NCT04436276

Janssen / J and J

U.S. Congressional Testimony

DNA plasmid vaccine Electroporation device

INO-4800

Phase 2
NCT04336410
Inovio Pharmaceuticals Same technology used for vaccine candidates against Lassa, Nipah, HIV, Filovirus, HPV, Zika

Hepatitis B

INACTIVATED SARS-CoV-2 VIRAL VECTOR    


ChiCTR2000031809 


 

Phase 3 

NCT04412538 

Beijing Institute of Biological Products/Wuhan Institute of Biological Products

 JAMA. Published online 13 Aug 2020. doi:10.1001/jama.2020.15543

SUB-UNIT VACCINE

     

 

NVX‑CoV2373

Phase 3

NCT04368988

Novavax Vaccine developed with and without novel adjuvant (Matrix-M)

 

RBDDimer

Phase 3

NCT04466085

Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd. Grown in CHO cells
  •  At least 70 other vaccine candidates in preclinical development listed on WHO website