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Covid-19 Pandemic:
Vaccine Development
Rachel Mackelprang, Ph.D.
California State University Northridge
Department of Biology
rachel.mackelprang@csun.edu
@rmackelprang
How we develop immunity
Virus is ingested by
specialized immune
system cells called
‘antigen presenting
cells’
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
How we develop immunity
Virus is ingested by
specialized immune
system cells called
‘antigen presenting
cells’
T-helper cell
Antigen presenting cells
display pieces of the virus to
activate T-helper cells
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
How we develop immunity
Virus is ingested by
specialized immune
system cells called
‘antigen presenting
cells’
T-helper cell
Antigen presenting cells
display pieces of the virus to
activate T-helper cells
T-cells activate other
immune responses
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
How we develop immunity
Virus is ingested by
specialized immune
system cells called
‘antigen presenting
cells’
T-helper cell
Antigen presenting cells
display pieces of the virus to
activate T-helper cells
Cytotoxic
T-cell
Cytotoxic T-cells identify
and destroy virus-
infected cells
T-cells activate other
immune responses
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
How we develop immunity
Virus is ingested by
specialized immune
system cells called
‘antigen presenting
cells’
T-helper cell
Antigen presenting cells
display pieces of the virus to
activate T-helper cells
Cytotoxic
T-cell
Cytotoxic T-cells identify
and destroy virus-
infected cells
B-cell
B-cells make antibodies that block the virus from
infecting more cells and mark it for destruction
T-cells activate other
immune responses
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
How we develop immunity
Virus is ingested by
specialized immune
system cells called
‘antigen presenting
cells’
T-helper cell
Antigen presenting cells
display pieces of the virus to
activate T-helper cells
Cytotoxic
T-cell
Cytotoxic T-cells identify
and destroy virus-
infected cells
Long-lived ‘memory’ B and T cells that
recognize the virus patrol the body for
months or years, providing immunity
B-cell
B-cells make antibodies that block the virus from
infecting more cells and mark it for destruction
T-cells activate other
immune responses
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
How vaccines work*
Weakened virus, dead virus, or parts of the virus are introduced into the patient.
Because it is inactive or in pieces, the patient doesn’t develop the disease.
Image credits: https://www.bbc.com/news/world-48186856
The Amoeba Sisters: https://www.amoebasisters.com/
*simplified
How vaccines work*
Image credit: The Amoeba Sisters: https://
www.amoebasisters.com/
Immune system cells mount a response to fight the attenuated virus
*simplified
How vaccines work*
The immune system retains memory of the pathogen and can mount an attack
more quickly and efficiently.
Image credit: The Amoeba Sisters: https://
www.amoebasisters.com/
*simplified
Types of vaccines: whole virus vaccines
These vaccines use a weakened or inactivated virus to produce an immune
response
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: whole virus vaccines
These vaccines use a weakened or inactivated virus to produce an immune
response
The virus is weakened or
inactivated
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: whole virus vaccines
These vaccines use a weakened or inactivated virus to produce an immune
response
The virus is weakened or
inactivated
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: whole virus vaccines
These vaccines use a weakened or inactivated virus to produce an immune
response
Antigen presenting cells take up the virus, break it into pieces,
and ‘present’ those pieces to other immune system cells.
The virus is weakened or
inactivated
Immune
response
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: whole virus vaccines
These vaccines use a weakened or inactivated virus to produce an immune
response
Examples: MMR, smallpox, yellow
fever, chickenpox, flu
Antigen presenting cells take up the virus, break it into pieces,
and ‘present’ those pieces to other immune system cells.
The virus is weakened or
inactivated
Immune
response
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: protein-based vaccines
Instead of the entire virus, only certain components that best stimulate the
immune system (called antigens) are used
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: protein-based vaccines
Instead of the entire virus, only certain components that best stimulate the
immune system (called antigens) are used
Pieces of viral proteins (such as the virus
spike or shell proteins) are administered
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: protein-based vaccines
Instead of the entire virus, only certain components that best stimulate the
immune system (called antigens) are used
Pieces of viral proteins (such as the virus
spike or shell proteins) are administered
Immune
response
Antigen presenting cells take up the viral
proteins, break them into pieces, and ‘present’
those pieces to other immune system cells.
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: protein-based vaccines
Instead of the entire virus, only certain components that best stimulate the
immune system (called antigens) are used
Pieces of viral proteins (such as the virus
spike or shell proteins) are administered
Immune
response
Antigen presenting cells take up the viral
proteins, break them into pieces, and ‘present’
those pieces to other immune system cells.
Examples: hepatitis B, HPV, whooping
cough, shingles
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: DNA vaccines
Vaccines that use genetic instructions (in the form of DNA) to make a viral protein
that prompts an immune response
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: DNA vaccines
Vaccines that use genetic instructions (in the form of DNA) to make a viral protein
that prompts an immune response
DNA encoding viral proteins (e.g.
the spike protein) is inserted into
a circular piece of DNA called a
plasmid
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: DNA vaccines
Vaccines that use genetic instructions (in the form of DNA) to make a viral protein
that prompts an immune response
DNA encoding viral proteins (e.g.
the spike protein) is inserted into
a circular piece of DNA called a
plasmid
mRNA
Our cells take up the
DNA and use it to make
viral proteins
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: DNA vaccines
Vaccines that use genetic instructions (in the form of DNA) to make a viral protein
that prompts an immune response
DNA encoding viral proteins (e.g.
the spike protein) is inserted into
a circular piece of DNA called a
plasmid
Immune
response
Antigen presenting cells take up the
viral proteins, break them into pieces,
and ‘present’ those pieces to other
immune system cells.
mRNA
Our cells take up the
DNA and use it to make
viral proteins
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: DNA vaccines
Vaccines that use genetic instructions (in the form of DNA) to make a viral protein
that prompts an immune response
Examples: West Nile virus in horses
None yet for human use
DNA encoding viral proteins (e.g.
the spike protein) is inserted into
a circular piece of DNA called a
plasmid
Immune
response
Antigen presenting cells take up the
viral proteins, break them into pieces,
and ‘present’ those pieces to other
immune system cells.
mRNA
Our cells take up the
DNA and use it to make
viral proteins
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: RNA vaccines
Vaccines that use genetic instructions (in the form of RNA) to make a viral protein
that prompts an immune response
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: RNA vaccines
Vaccines that use genetic instructions (in the form of RNA) to make a viral protein
that prompts an immune response
RNA encoding viral proteins (e.g.
the spike protein) is encased in a
lipid coat so it can enter cells
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: RNA vaccines
Vaccines that use genetic instructions (in the form of RNA) to make a viral protein
that prompts an immune response
RNA encoding viral proteins (e.g.
the spike protein) is encased in a
lipid coat so it can enter cells
Our cells take up the
RNA and use it to make
viral proteins
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: RNA vaccines
Vaccines that use genetic instructions (in the form of RNA) to make a viral protein
that prompts an immune response
Immune
response
Antigen presenting cells take up the
viral proteins, break them into pieces,
and ‘present’ those pieces to other
immune system cells.
RNA encoding viral proteins (e.g.
the spike protein) is encased in a
lipid coat so it can enter cells
Our cells take up the
RNA and use it to make
viral proteins
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: RNA vaccines
Vaccines that use genetic instructions (in the form of RNA) to make a viral protein
that prompts an immune response
RNA vaccines are still under development and none have yet been approved for use in humans
Immune
response
Antigen presenting cells take up the
viral proteins, break them into pieces,
and ‘present’ those pieces to other
immune system cells.
RNA encoding viral proteins (e.g.
the spike protein) is encased in a
lipid coat so it can enter cells
Our cells take up the
RNA and use it to make
viral proteins
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: viral vectors
These vaccines use a different virus (that doesn’t cause disease) to deliver
coronavirus genes into the cell and provoke an immune response
Genes encoding viral proteins
(e.g. the spike protein) are placed
into a non-disease causing virus
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Types of vaccines: viral vectors
These vaccines use a different virus (that doesn’t cause disease) to deliver
coronavirus genes into the cell and provoke an immune response
Genes encoding viral proteins
(e.g. the spike protein) are placed
into a non-disease causing virus
The non-disease
causing virus replicates
within our cells
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Immune
response
Antigen presenting cells take up the
virus, break it into pieces (which
include pieces of coronavirus
proteins), and ‘present’ those pieces
to other immune system cells.
Types of vaccines: viral vectors
These vaccines use a different virus (that doesn’t cause disease) to deliver
coronavirus genes into the cell and provoke an immune response
Genes encoding viral proteins
(e.g. the spike protein) are placed
into a non-disease causing virus
The non-disease
causing virus replicates
within our cells
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Immune
response
Antigen presenting cells take up the
virus, break it into pieces (which
include pieces of coronavirus
proteins), and ‘present’ those pieces
to other immune system cells.
Types of vaccines: viral vectors
These vaccines use a different virus (that doesn’t cause disease) to deliver
coronavirus genes into the cell and provoke an immune response
Example: Newly approved
Ebola vaccine
Genes encoding viral proteins
(e.g. the spike protein) are placed
into a non-disease causing virus
The non-disease
causing virus replicates
within our cells
Content: https://www.nature.com/articles/d41586-020-01221-y
Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Stages of vaccine development
Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance
Safety &
dosage
testing
Expanded
safety trials
Large-scale
efficacy
tests
Approved
for limited
use
Animal trials
Usually it takes years to develop a vaccine, but scientists are racing to produce a
safe and effective vaccine by next year
1-10 years 2-3 years 2-4 years > 1 year
https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1
https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Stages of vaccine development*
Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance
Safety &
dosage
testing
Expanded
safety trials
Large-scale
efficacy
tests
Approved
for limited
use
Animal trials
Usually it takes years to develop a vaccine, but scientists are racing to produce a
safe and effective vaccine by next year
135+ 21 13 8 2 0
1-10 years 2-3 years 2-4 years > 1 year
*August 23rd 2020
https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1
https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Stages of vaccine development*
Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance
Safety &
dosage
testing
Expanded
safety trials
Large-scale
efficacy
tests
Approved
for limited
use
Animal trials
Usually it takes years to develop a vaccine, but scientists are racing to produce a
safe and effective vaccine by next year
135+ 21 13 8 2 0
Preclinical testing: scientists give the vaccine to animals such as mice or monkeys to see
if it produces an immune response
*August 23rd 2020
https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1
https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Stages of vaccine development*
Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance
Safety &
dosage
testing
Expanded
safety trials
Large-scale
efficacy
tests
Approved
for limited
use
Animal trials
Usually it takes years to develop a vaccine, but scientists are racing to produce a
safe and effective vaccine by next year
135+ 21 13 8 2 0
Phase I safety trials: scientists give the vaccine to a small number of people to test safety
and dosage and to confirm that it stimulates the immune system
*August 23rd 2020
https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1
https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Stages of vaccine development*
Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance
Safety &
dosage
testing
Expanded
safety trials
Large-scale
efficacy
tests
Approved
for limited
use
Animal trials
Usually it takes years to develop a vaccine, but scientists are racing to produce a
safe and effective vaccine by next year
135+ 21 13 8 2 0
Phase II expanded trials: scientists give the vaccine to hundreds of people split into
groups, such as children and the elderly, to see if the vaccine acts differently in them. These
trials further test the vaccine’s safety and ability to stimulate the immune system.
*August 23rd 2020
https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1
https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Stages of vaccine development*
Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance
Safety &
dosage
testing
Expanded
safety trials
Large-scale
efficacy
tests
Approved
for limited
use
Animal trials
Usually it takes years to develop a vaccine, but scientists are racing to produce a
safe and effective vaccine by next year
135+ 21 13 8 2 0
Phase II expanded trials: To accelerate the vaccine development timeline, there are
several vaccines combining Phase I and II trials
*August 23rd 2020
https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1
https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Stages of vaccine development*
Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance
Safety &
dosage
testing
Expanded
safety trials
Large-scale
efficacy
tests
Approved
for limited
use
Animal trials
Usually it takes years to develop a vaccine, but scientists are racing to produce a
safe and effective vaccine by next year
135+ 21 13 8 2 0
Phase III efficacy trials: scientists give the vaccine to thousands of people and wait to see
how many become infected compared with volunteers who received a placebo. These trials
can determine if the vaccine protects against the coronavirus
*August 23rd 2020
https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1
https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Stages of vaccine development*
Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance
Safety &
dosage
testing
Expanded
safety trials
Large-scale
efficacy
tests
Approved
for limited
use
Animal trials
Usually it takes years to develop a vaccine, but scientists are racing to produce a
safe and effective vaccine by next year
135+ 21 13 8 2 0
Approval: Regulators in each country review the trial results and decide whether to approve
the vaccine or not. During a pandemic, a vaccine may receive emergency use authorization
before getting formal approval.
*August 23rd 2020
https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1
https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Stages of vaccine development*
Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance
Safety &
dosage
testing
Expanded
safety trials
Large-scale
efficacy
tests
Approved
for limited
use
Animal trials
Usually it takes years to develop a vaccine, but scientists are racing to produce a
safe and effective vaccine by next year
135+ 21 13 8 2 0
There is 1 vaccine that is currently in Phase III trials and has limited approval for use in
the Chinese military as a “specially needed drug.”
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31605-6/fulltext
*August 23rd 2020
https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1
https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Stages of vaccine development*
Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance
Safety &
dosage
testing
Expanded
safety trials
Large-scale
efficacy
tests
Approved
for limited
use
Animal trials
Usually it takes years to develop a vaccine, but scientists are racing to produce a
safe and effective vaccine by next year
135+ 21 13 8 2 0
Russia approved a vaccine that has completed Phase II trials (but hasn’t begun Phase III). However, trial
data have not been published and vaccine experts worry about about safety and efficacy.
https://edition.cnn.com/2020/08/11/europe/russia-coronavirus-vaccine-putin-intl/index.html
https://www.bbc.com/news/world-europe-53751017
*August 23rd 2020
https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1
https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
Example of a promising candidate
mRNA vaccine. Teaches human cells to build the spike proteins, which
triggers an immune response.
Results from phase I trial: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022483?articleTools=true
Example of a promising candidate
mRNA vaccine. Teaches human cells to build the spike proteins, which
triggers an immune response.
Phase I trial results published on July 14th 2020
Safety &
dosage
testing
Results from phase I trial: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022483?articleTools=true
Example of a promising candidate
mRNA vaccine. Teaches human cells to build the spike proteins, which
triggers an immune response.
Phase I trial results published on July 14th 2020
Safety &
dosage
testing
Generally safe and well-tolerated, but ~1/2 had some mild/moderate side effects (e.g.,
fatigue, headache, chills). High dose that caused the strongest side effects won’t be
used in subsequent trials.
Results from phase I trial: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022483?articleTools=true
Example of a promising candidate
mRNA vaccine. Teaches human cells to build the spike proteins, which
triggers an immune response.
Phase I trial results published on July 14th 2020
Safety &
dosage
testing
Generally safe and well-tolerated, but ~1/2 had some mild/moderate side effects (e.g.,
fatigue, headache, chills). High dose that caused the strongest side effects won’t be
used in subsequent trials.
Phase II is ongoing. Phase III trials started July 27th, 2020 with a target of
30,000 individuals.
Large-scale
efficacy
tests
Results from phase I trial: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022483?articleTools=true
Moderna vaccine: phase I experiment
Results from phase I trial: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022483?articleTools=true
45 healthy adults
18-55 years of age
25 µg dose
100 µg dose
250 µg dose
15 individuals
15 individuals
15 individuals
Day1
Z
25 µg dose
100 µg dose
250 µg dose
Day29
Moderna vaccine: phase I results*
Key result: the vaccine provoked a strong immune response
Antibodiesproduced
Less
More
Pre-injection
Recovered
patient
All results from phase I trial: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022483?articleTools=true
*Simplified. See linked
paper for full results
Moderna vaccine: phase I results*
Key result: the vaccine provoked a strong immune response
Antibodiesproduced
Less
More
Pre-injection
Recovered
patient
After 1st dose
All results from phase I trial: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022483?articleTools=true
*Simplified. See linked
paper for full results
Moderna vaccine: phase I results*
Key result: the vaccine provoked a strong immune response
Antibodiesproduced
Less
More
Pre-injection
Recovered
patient
After 1st dose
After 2nd
dose
All results from phase I trial: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022483?articleTools=true
*Simplified. See linked
paper for full results
Moderna vaccine: phase I results*
Key result: the vaccine provoked a strong immune response
Antibodiesproduced
Less
More
Pre-injection
Recovered
patient
After 1st dose
After 2nd
dose
All results from phase I trial: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022483?articleTools=true
*Simplified. See linked
paper for full results
Note that Phase I trials do not evaluate efficacy. Producing an immune
response does not guarantee immunity if exposed to the virus. Phase III
trials are designed for efficacy testing.

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Covid-19 vaccine development

  • 1. Covid-19 Pandemic: Vaccine Development Rachel Mackelprang, Ph.D. California State University Northridge Department of Biology rachel.mackelprang@csun.edu @rmackelprang
  • 2. How we develop immunity Virus is ingested by specialized immune system cells called ‘antigen presenting cells’ Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 3. How we develop immunity Virus is ingested by specialized immune system cells called ‘antigen presenting cells’ T-helper cell Antigen presenting cells display pieces of the virus to activate T-helper cells Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 4. How we develop immunity Virus is ingested by specialized immune system cells called ‘antigen presenting cells’ T-helper cell Antigen presenting cells display pieces of the virus to activate T-helper cells T-cells activate other immune responses Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 5. How we develop immunity Virus is ingested by specialized immune system cells called ‘antigen presenting cells’ T-helper cell Antigen presenting cells display pieces of the virus to activate T-helper cells Cytotoxic T-cell Cytotoxic T-cells identify and destroy virus- infected cells T-cells activate other immune responses Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 6. How we develop immunity Virus is ingested by specialized immune system cells called ‘antigen presenting cells’ T-helper cell Antigen presenting cells display pieces of the virus to activate T-helper cells Cytotoxic T-cell Cytotoxic T-cells identify and destroy virus- infected cells B-cell B-cells make antibodies that block the virus from infecting more cells and mark it for destruction T-cells activate other immune responses Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 7. How we develop immunity Virus is ingested by specialized immune system cells called ‘antigen presenting cells’ T-helper cell Antigen presenting cells display pieces of the virus to activate T-helper cells Cytotoxic T-cell Cytotoxic T-cells identify and destroy virus- infected cells Long-lived ‘memory’ B and T cells that recognize the virus patrol the body for months or years, providing immunity B-cell B-cells make antibodies that block the virus from infecting more cells and mark it for destruction T-cells activate other immune responses Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 8. How vaccines work* Weakened virus, dead virus, or parts of the virus are introduced into the patient. Because it is inactive or in pieces, the patient doesn’t develop the disease. Image credits: https://www.bbc.com/news/world-48186856 The Amoeba Sisters: https://www.amoebasisters.com/ *simplified
  • 9. How vaccines work* Image credit: The Amoeba Sisters: https:// www.amoebasisters.com/ Immune system cells mount a response to fight the attenuated virus *simplified
  • 10. How vaccines work* The immune system retains memory of the pathogen and can mount an attack more quickly and efficiently. Image credit: The Amoeba Sisters: https:// www.amoebasisters.com/ *simplified
  • 11. Types of vaccines: whole virus vaccines These vaccines use a weakened or inactivated virus to produce an immune response Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 12. Types of vaccines: whole virus vaccines These vaccines use a weakened or inactivated virus to produce an immune response The virus is weakened or inactivated Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 13. Types of vaccines: whole virus vaccines These vaccines use a weakened or inactivated virus to produce an immune response The virus is weakened or inactivated Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 14. Types of vaccines: whole virus vaccines These vaccines use a weakened or inactivated virus to produce an immune response Antigen presenting cells take up the virus, break it into pieces, and ‘present’ those pieces to other immune system cells. The virus is weakened or inactivated Immune response Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 15. Types of vaccines: whole virus vaccines These vaccines use a weakened or inactivated virus to produce an immune response Examples: MMR, smallpox, yellow fever, chickenpox, flu Antigen presenting cells take up the virus, break it into pieces, and ‘present’ those pieces to other immune system cells. The virus is weakened or inactivated Immune response Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 16. Types of vaccines: protein-based vaccines Instead of the entire virus, only certain components that best stimulate the immune system (called antigens) are used Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 17. Types of vaccines: protein-based vaccines Instead of the entire virus, only certain components that best stimulate the immune system (called antigens) are used Pieces of viral proteins (such as the virus spike or shell proteins) are administered Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 18. Types of vaccines: protein-based vaccines Instead of the entire virus, only certain components that best stimulate the immune system (called antigens) are used Pieces of viral proteins (such as the virus spike or shell proteins) are administered Immune response Antigen presenting cells take up the viral proteins, break them into pieces, and ‘present’ those pieces to other immune system cells. Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 19. Types of vaccines: protein-based vaccines Instead of the entire virus, only certain components that best stimulate the immune system (called antigens) are used Pieces of viral proteins (such as the virus spike or shell proteins) are administered Immune response Antigen presenting cells take up the viral proteins, break them into pieces, and ‘present’ those pieces to other immune system cells. Examples: hepatitis B, HPV, whooping cough, shingles Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 20. Types of vaccines: DNA vaccines Vaccines that use genetic instructions (in the form of DNA) to make a viral protein that prompts an immune response Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 21. Types of vaccines: DNA vaccines Vaccines that use genetic instructions (in the form of DNA) to make a viral protein that prompts an immune response DNA encoding viral proteins (e.g. the spike protein) is inserted into a circular piece of DNA called a plasmid Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 22. Types of vaccines: DNA vaccines Vaccines that use genetic instructions (in the form of DNA) to make a viral protein that prompts an immune response DNA encoding viral proteins (e.g. the spike protein) is inserted into a circular piece of DNA called a plasmid mRNA Our cells take up the DNA and use it to make viral proteins Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 23. Types of vaccines: DNA vaccines Vaccines that use genetic instructions (in the form of DNA) to make a viral protein that prompts an immune response DNA encoding viral proteins (e.g. the spike protein) is inserted into a circular piece of DNA called a plasmid Immune response Antigen presenting cells take up the viral proteins, break them into pieces, and ‘present’ those pieces to other immune system cells. mRNA Our cells take up the DNA and use it to make viral proteins Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 24. Types of vaccines: DNA vaccines Vaccines that use genetic instructions (in the form of DNA) to make a viral protein that prompts an immune response Examples: West Nile virus in horses None yet for human use DNA encoding viral proteins (e.g. the spike protein) is inserted into a circular piece of DNA called a plasmid Immune response Antigen presenting cells take up the viral proteins, break them into pieces, and ‘present’ those pieces to other immune system cells. mRNA Our cells take up the DNA and use it to make viral proteins Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 25. Types of vaccines: RNA vaccines Vaccines that use genetic instructions (in the form of RNA) to make a viral protein that prompts an immune response Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 26. Types of vaccines: RNA vaccines Vaccines that use genetic instructions (in the form of RNA) to make a viral protein that prompts an immune response RNA encoding viral proteins (e.g. the spike protein) is encased in a lipid coat so it can enter cells Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 27. Types of vaccines: RNA vaccines Vaccines that use genetic instructions (in the form of RNA) to make a viral protein that prompts an immune response RNA encoding viral proteins (e.g. the spike protein) is encased in a lipid coat so it can enter cells Our cells take up the RNA and use it to make viral proteins Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 28. Types of vaccines: RNA vaccines Vaccines that use genetic instructions (in the form of RNA) to make a viral protein that prompts an immune response Immune response Antigen presenting cells take up the viral proteins, break them into pieces, and ‘present’ those pieces to other immune system cells. RNA encoding viral proteins (e.g. the spike protein) is encased in a lipid coat so it can enter cells Our cells take up the RNA and use it to make viral proteins Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 29. Types of vaccines: RNA vaccines Vaccines that use genetic instructions (in the form of RNA) to make a viral protein that prompts an immune response RNA vaccines are still under development and none have yet been approved for use in humans Immune response Antigen presenting cells take up the viral proteins, break them into pieces, and ‘present’ those pieces to other immune system cells. RNA encoding viral proteins (e.g. the spike protein) is encased in a lipid coat so it can enter cells Our cells take up the RNA and use it to make viral proteins Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 30. Types of vaccines: viral vectors These vaccines use a different virus (that doesn’t cause disease) to deliver coronavirus genes into the cell and provoke an immune response Genes encoding viral proteins (e.g. the spike protein) are placed into a non-disease causing virus Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 31. Types of vaccines: viral vectors These vaccines use a different virus (that doesn’t cause disease) to deliver coronavirus genes into the cell and provoke an immune response Genes encoding viral proteins (e.g. the spike protein) are placed into a non-disease causing virus The non-disease causing virus replicates within our cells Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 32. Immune response Antigen presenting cells take up the virus, break it into pieces (which include pieces of coronavirus proteins), and ‘present’ those pieces to other immune system cells. Types of vaccines: viral vectors These vaccines use a different virus (that doesn’t cause disease) to deliver coronavirus genes into the cell and provoke an immune response Genes encoding viral proteins (e.g. the spike protein) are placed into a non-disease causing virus The non-disease causing virus replicates within our cells Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 33. Immune response Antigen presenting cells take up the virus, break it into pieces (which include pieces of coronavirus proteins), and ‘present’ those pieces to other immune system cells. Types of vaccines: viral vectors These vaccines use a different virus (that doesn’t cause disease) to deliver coronavirus genes into the cell and provoke an immune response Example: Newly approved Ebola vaccine Genes encoding viral proteins (e.g. the spike protein) are placed into a non-disease causing virus The non-disease causing virus replicates within our cells Content: https://www.nature.com/articles/d41586-020-01221-y Virus image: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 34. Stages of vaccine development Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance Safety & dosage testing Expanded safety trials Large-scale efficacy tests Approved for limited use Animal trials Usually it takes years to develop a vaccine, but scientists are racing to produce a safe and effective vaccine by next year 1-10 years 2-3 years 2-4 years > 1 year https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1 https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 35. Stages of vaccine development* Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance Safety & dosage testing Expanded safety trials Large-scale efficacy tests Approved for limited use Animal trials Usually it takes years to develop a vaccine, but scientists are racing to produce a safe and effective vaccine by next year 135+ 21 13 8 2 0 1-10 years 2-3 years 2-4 years > 1 year *August 23rd 2020 https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1 https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 36. Stages of vaccine development* Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance Safety & dosage testing Expanded safety trials Large-scale efficacy tests Approved for limited use Animal trials Usually it takes years to develop a vaccine, but scientists are racing to produce a safe and effective vaccine by next year 135+ 21 13 8 2 0 Preclinical testing: scientists give the vaccine to animals such as mice or monkeys to see if it produces an immune response *August 23rd 2020 https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1 https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 37. Stages of vaccine development* Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance Safety & dosage testing Expanded safety trials Large-scale efficacy tests Approved for limited use Animal trials Usually it takes years to develop a vaccine, but scientists are racing to produce a safe and effective vaccine by next year 135+ 21 13 8 2 0 Phase I safety trials: scientists give the vaccine to a small number of people to test safety and dosage and to confirm that it stimulates the immune system *August 23rd 2020 https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1 https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 38. Stages of vaccine development* Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance Safety & dosage testing Expanded safety trials Large-scale efficacy tests Approved for limited use Animal trials Usually it takes years to develop a vaccine, but scientists are racing to produce a safe and effective vaccine by next year 135+ 21 13 8 2 0 Phase II expanded trials: scientists give the vaccine to hundreds of people split into groups, such as children and the elderly, to see if the vaccine acts differently in them. These trials further test the vaccine’s safety and ability to stimulate the immune system. *August 23rd 2020 https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1 https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 39. Stages of vaccine development* Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance Safety & dosage testing Expanded safety trials Large-scale efficacy tests Approved for limited use Animal trials Usually it takes years to develop a vaccine, but scientists are racing to produce a safe and effective vaccine by next year 135+ 21 13 8 2 0 Phase II expanded trials: To accelerate the vaccine development timeline, there are several vaccines combining Phase I and II trials *August 23rd 2020 https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1 https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 40. Stages of vaccine development* Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance Safety & dosage testing Expanded safety trials Large-scale efficacy tests Approved for limited use Animal trials Usually it takes years to develop a vaccine, but scientists are racing to produce a safe and effective vaccine by next year 135+ 21 13 8 2 0 Phase III efficacy trials: scientists give the vaccine to thousands of people and wait to see how many become infected compared with volunteers who received a placebo. These trials can determine if the vaccine protects against the coronavirus *August 23rd 2020 https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1 https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 41. Stages of vaccine development* Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance Safety & dosage testing Expanded safety trials Large-scale efficacy tests Approved for limited use Animal trials Usually it takes years to develop a vaccine, but scientists are racing to produce a safe and effective vaccine by next year 135+ 21 13 8 2 0 Approval: Regulators in each country review the trial results and decide whether to approve the vaccine or not. During a pandemic, a vaccine may receive emergency use authorization before getting formal approval. *August 23rd 2020 https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1 https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 42. Stages of vaccine development* Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance Safety & dosage testing Expanded safety trials Large-scale efficacy tests Approved for limited use Animal trials Usually it takes years to develop a vaccine, but scientists are racing to produce a safe and effective vaccine by next year 135+ 21 13 8 2 0 There is 1 vaccine that is currently in Phase III trials and has limited approval for use in the Chinese military as a “specially needed drug.” https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31605-6/fulltext *August 23rd 2020 https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1 https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 43. Stages of vaccine development* Exploratory Preclinical Phase I Phase II Phase III Approval Surveillance Safety & dosage testing Expanded safety trials Large-scale efficacy tests Approved for limited use Animal trials Usually it takes years to develop a vaccine, but scientists are racing to produce a safe and effective vaccine by next year 135+ 21 13 8 2 0 Russia approved a vaccine that has completed Phase II trials (but hasn’t begun Phase III). However, trial data have not been published and vaccine experts worry about about safety and efficacy. https://edition.cnn.com/2020/08/11/europe/russia-coronavirus-vaccine-putin-intl/index.html https://www.bbc.com/news/world-europe-53751017 *August 23rd 2020 https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf?ua=1 https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  • 44. Example of a promising candidate mRNA vaccine. Teaches human cells to build the spike proteins, which triggers an immune response. Results from phase I trial: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022483?articleTools=true
  • 45. Example of a promising candidate mRNA vaccine. Teaches human cells to build the spike proteins, which triggers an immune response. Phase I trial results published on July 14th 2020 Safety & dosage testing Results from phase I trial: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022483?articleTools=true
  • 46. Example of a promising candidate mRNA vaccine. Teaches human cells to build the spike proteins, which triggers an immune response. Phase I trial results published on July 14th 2020 Safety & dosage testing Generally safe and well-tolerated, but ~1/2 had some mild/moderate side effects (e.g., fatigue, headache, chills). High dose that caused the strongest side effects won’t be used in subsequent trials. Results from phase I trial: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022483?articleTools=true
  • 47. Example of a promising candidate mRNA vaccine. Teaches human cells to build the spike proteins, which triggers an immune response. Phase I trial results published on July 14th 2020 Safety & dosage testing Generally safe and well-tolerated, but ~1/2 had some mild/moderate side effects (e.g., fatigue, headache, chills). High dose that caused the strongest side effects won’t be used in subsequent trials. Phase II is ongoing. Phase III trials started July 27th, 2020 with a target of 30,000 individuals. Large-scale efficacy tests Results from phase I trial: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022483?articleTools=true
  • 48. Moderna vaccine: phase I experiment Results from phase I trial: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022483?articleTools=true 45 healthy adults 18-55 years of age 25 µg dose 100 µg dose 250 µg dose 15 individuals 15 individuals 15 individuals Day1 Z 25 µg dose 100 µg dose 250 µg dose Day29
  • 49. Moderna vaccine: phase I results* Key result: the vaccine provoked a strong immune response Antibodiesproduced Less More Pre-injection Recovered patient All results from phase I trial: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022483?articleTools=true *Simplified. See linked paper for full results
  • 50. Moderna vaccine: phase I results* Key result: the vaccine provoked a strong immune response Antibodiesproduced Less More Pre-injection Recovered patient After 1st dose All results from phase I trial: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022483?articleTools=true *Simplified. See linked paper for full results
  • 51. Moderna vaccine: phase I results* Key result: the vaccine provoked a strong immune response Antibodiesproduced Less More Pre-injection Recovered patient After 1st dose After 2nd dose All results from phase I trial: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022483?articleTools=true *Simplified. See linked paper for full results
  • 52. Moderna vaccine: phase I results* Key result: the vaccine provoked a strong immune response Antibodiesproduced Less More Pre-injection Recovered patient After 1st dose After 2nd dose All results from phase I trial: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022483?articleTools=true *Simplified. See linked paper for full results Note that Phase I trials do not evaluate efficacy. Producing an immune response does not guarantee immunity if exposed to the virus. Phase III trials are designed for efficacy testing.