Saturday, September 5, 2020

The Washington Post Vaccine Tracker

New technologies

Advancements in science and technology have given researchers new tools to try against the coronavirus. Scientists can deliver genetic material into the body’s cells, turning them into vaccine factories and skipping time-consuming steps such as manufacturing viral proteins or growing the whole virus in chicken eggs.

Technology used:

Nucleic acid
Viral-vectored
Subunit
Virus
Other
Pre-clinical
Phase 1
Phase 2
Phase 3
Approved

The core of the coronavirus SARS-CoV-2 is a single strip of ribonucleic acid (RNA) surrounded by a protein shell. The virus is named for the iconic spikes that project from its center like a crown, or “corona” in Latin. These spike proteins aren’t just decoration. They are critical for the virus to get inside cells and make copies of itself.

Vaccines work by teaching the body’s immune system to recognize and block viruses, and each category of vaccine works under this basic principle. Vaccine technology aims to activate the immune system’s T-helper cells, which are responsible for detecting the presence of a virus. They instruct B-cells to create antibodies that block the virus from being able to replicate and T-killer cells to destroy infected cells. Some vaccines may activate only part of this immune response.

Coronavirus

SARS-CoV-2

Spike protein

M Protein

SARS-CoV-2

copies

RNA

ACE2

receptor

RNA

Proteins

SARS-CoV-2 uses 

its spike to bind to 

the ACE2 receptor, 

allowing access 

into the cell.

The virus’s RNA is 

released into the 

cell. The cell reads 

the RNA and 

makes proteins.

The viral 

proteins are 

then assembled 

into new copies 

of the virus.

The copies 

are released 

and go on to 

infect more 

cells.

Here is a look at how different vaccine technologies being developed around the world would ideally elicit an immune response to prevent SARS-CoV-2 in humans. Each vaccine may vary somewhat in how it works, but each would generally follow these steps.

Vaccines using nucleic acid (DNA and RNA)

DNA vaccines contain genetic material that carries the blueprint for the spike protein. To get the DNA into cells, researchers use an electrical pulse to disrupt the cell membrane. Once inside, the DNA is used as a template to create spike protein.

RNA vaccines contain a strip of genetic material within a fat bubble. Once inside the cell, the RNA generates a protein found on the surface of the virus. The immune system, presented with the protein, learns to recognize the virus.

These vaccines have the advantage of speed — they can be quickly designed and manufactured. But they have never been approved for use outside of medical research and will likely require two doses.

An electric pulse allows DNA into the cell’s nucleus where it forms mRNA, then creates spike proteins 

Antigen-presenting cells (APCs) consume the viral proteins and pass viral peptides to T-helper cells

Cytotoxic 

T cells may eliminate virus-infected cells

DNA vaccine

Spike gene

on DNA

Cytotoxic

T cell

Spike protein

Viral

peptide

Cell

T-helper

cell

APC

B-cell

A lipid shell delivers mRNA into the cell, where it is used to produce proteins

Antibodies from B-cells may block the virus 

mRNA in

lipid shell

RNA vaccine

Nucleic acid vaccines, developed by...

Moderna; National Institutes of Health
PC
P1
P2
P3
A
Pfizer; BioNTech; Fosun Pharma 
PC
P1
P2
P3
A
AnGes; Osaka University; Takara Bio
PC
P1
P2
P3
A
Arcturus Therapeutics; Duke-NUS
PC
P1
P2
P3
A
*Vaccine currently in distribution that has not been fully tested.

Viral-vectored vaccines

Some vaccines use a virus that has been engineered to be harmless to ferry a gene from the coronavirus into cells. The gene codes for a distinctive part of the coronavirus, and the immune system learns to recognize it.

Viral-vectored vaccines can be designed quickly. One concern is that people can develop immunity to the viral vector, making this approach potentially less useful if booster shots need to be given.

Replicating

viral vector

Replicating viral vector infects cell, produces SARS-CoV-2 antigen and additional vectors

SARS-CoV-2 gene

in a different virus

Cytotoxic

T cell

Vectors

Cell

Viral

peptide

Antigen

T-helper

cell

APC

B-cell

SARS-CoV-2 gene

in a different virus

Non-replicating viral vector infects cells, produces SARS-CoV-2 antigen

Non-replicating

viral vector

Viral-vectored vaccines, developed by...

CanSino Biologics; Beijing Institute of Biotechnology*
PC
P1
P2
P3
A
University of Oxford, Oxford Biomedica, Vaccines Manufacturing and Innovation Centre, Pall Life Sciences, Cobra Biologics, HalixBV, Advent s.r.l., Merck KGaA, the Serum Institute, Vaccitech, Catalent, and AstraZeneca; IQVIA
PC
P1
P2
P3
A
Gamaleya Research Institute*
PC
P1
P2
P3
A
Janssen Pharmaceutical
PC
P1
P2
P3
A
*Vaccine currently in distribution that has not been fully tested.

Subunit vaccines

Some traditional vaccines work by delivering viral proteins to cells. The technologies to manufacture those protein fragments vary, but companies are using insect cells and yeast. The hepatitis B vaccine relies on a viral protein created by genetically engineered yeast.

Empty viral shells look like the virus but are not harmful because they have no genetic material

Virus-like

particles

Empty viral shell

Cytotoxic

T cell

Viral

peptide

T-helper

cell

APC

B-cell

SARS-CoV-2 proteins

Specific protein subunits, such as the spike protein, enter the body

Protein

subunits

Subunit vaccines, developed by...

Anhui Zhifei Longcom; Chinese Academy of Sciences
PC
P1
P2
P3
A
Federal Budgetary Research Institution (FBRI) State Research Center of Virology and Biotechnology "VECTOR"
PC
P1
P2
P3
A
Instituto Finlay de Vacunas
PC
P1
P2
P3
A
Novavax; Emergent BioSolutions; Praha Vaccines; Serum Institute of India; AGC Biologics; Fujifilm Diosynth Biotechnologies; SK bioscience
PC
P1
P2
P3
A
*Vaccine currently in distribution that has not been fully tested.

Weakened or inactivated virus vaccines

In a more old-fashioned approach, the virus is weakened so that it does not cause disease, but still triggers the immune system’s defenses. The vaccine for measles, mumps and rubella uses this approach.

Inactivated virus vaccines contain dead virus, incapable of infecting people but still able to instruct the immune system how to mount a defensive reaction against an infection. The polio vaccine invented by Jonas Salk used this approach, and flu vaccines use this technology.

These vaccines typically take longer to manufacture.

Weakened

virus

Weakened virus replicates in human cells.

Weakened virus

Replicated

virus

Cytotoxic

T cell

Viral

peptide

Cell

T-helper

cell

APC

B-cell

Dead virus from the vaccine enters the body

Dead virus

Inactivated

virus

Weakened and inactivated virus vaccines, developed by...

Beijing Institute of Biological Products; Sinopharm
PC
P1
P2
P3
A
Sinopharm
PC
P1
P2
P3
A
Sinovac
PC
P1
P2
P3
A
Bharat Biotech
PC
P1
P2
P3
A
*Vaccine currently in distribution that has not been fully tested.

Other vaccines

Information on the technology platform being used was not available for all the experimental vaccines. Some vaccines being tested do not specifically target the coronavirus, but aim to increase the body’s first line of immune defenses.

CORRECTION

An earlier version of this article erroneously listed a vaccine developed by Novavax to be in Phase 3 (Aug. 13, 2020). An earlier version of the graphic illustrating how subunit vaccines work was mislabeled (Aug. 14, 2020).

About this story

Data for vaccine developments comes from FasterCures, a center for the Milken Institute, and Post reporting. FasterCures tracks publicly available information on covid-19 vaccine development from a variety of sources, such as preprints from medRxiv and bioRxiv; clinical trial registries from the United States, European Union and the World Health Organization's International Clinical Trials Registry Platform, which includes clinical trial information from China; WHO documents on covid-19; and news reports.

Other sources: Dr. Angela Rasmussen, Columbia University, Center for Infection and Immunity; National Institutes of Health; Centers for Disease Control and Prevention; Nature Research.

Have we missed something? Please email us with updates and questions.

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Aaron Steckelberg is a senior graphics editor who creates maps, charts and diagrams that provide greater depth and context to stories over a wide range of topics. He has worked at the Post since 2016. 
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