Chemistry for Allied Health Professionals

MLS1-5 / LECTURE / CONTENTS ARE PPT AND LECTURE BASED

VACCINES HOW ARE VACCINES MADE?
I. Attenuated vaccines
TOPIC OUTLINE II. Inactivated vaccines
1 The Beginning of Vaccines III. Subunit vaccines
2 What is a vaccine? How are vaccines made? IV. Vector vaccines
3 Types of vaccines V. DNA and mRNA vaccines
4 Requirements for Vaccine Development
5 Stages of Vaccine Development
6 How do vaccines work? HOW ARE VACCINES MADE?
ATTENUATED → live bacterium or virus is used,
THE BEGINNING OF VACCINES VACCINES but in a weakened state.
→ replicating
EDWARD JENNER → unable to cause disease.
→ “Father of Immunization” → long lasting immunity with one
→ discovered the principles of immunization. dose
→ smallpox vaccine (first world’s vaccine)
FOR: Measles/Mumps/Rubella
(MMR); chickenpox; BCG; Yellow
LOUIS PASTEUR fever
→ the first vaccine against rabies.
→ treated 350 with his rabies vaccine, IMMUNE RESPONSE:
of whom only one developed rabies by the end of ✓ live microorganisms provide continual
1885. antigenic stimulation, giving sufficient time for
memory cell production
✓ attenuated pathogens – capable of
TIMELINE OF OTHER VACCINES replicating within host cells
✓ excellent immune response
1932 Yellow fever
SAFETY AND STABILITY:
1945 Influenza
→ attenuated pathogens: can revert to original
1952 Polio form and cause disease
1954 Japanese Encephalitis → potential harm to individuals with
1957 Adenovirus 4 and 7 compromised immune systems (e.g. HIV)
1962 Oral polio → sustained infection (BCG – local
1964 Measles lymphadenitis)
1967 Mumps → contamination of tissue culture
1970 Rubella → immunization errors (reconstitution, cold
1974 Chicken pox chain)
1977 Pneumonia → not given during pregnancy
1978 Meningitis
1981 Hepatitis B **less safe compared to inactivated vaccines
1992 Hepatitis A
1998 Rotavirus VACCINES RECOMMENDED BY WHO THAT USES
LAV TECHNOLOGY
WHAT IS A VACCINE? - Tuberculosis (BCG)
- Oral Polio Vaccine
VACCINE - Measles
→ suspension of killed or attenuated infectious - Rotavirus
agents administered to establish resistance to - Yellow fever
the disease. INACTIVATED → killed by heat or chemicals
→ method of administering vaccines: VACCINES → nonreplicating
- by injection → less efficacious than live
- by mouth vaccines
- by nasal spray → multiple doses or periodic
booster shots
→ short-lasting immunity
FOR: Flu shot, polio, rabies, pertussis

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MLS1-5 / LECTURE / CONTENTS ARE PPT AND LECTURE BASED

IMMUNE RESPONSE: → work slightly different

✓ May not always induce an immune response compared to traditional
at first dose vaccines.
✓ May not be long-lived, requiring several doses → uses part of the virus’ own
of vaccine genes to stimulate an immune
✓ Less strong immune response compared to response.
live vaccines → carry the genetic instructions
for the host’s cells to make
SAFETY AND STABILITY: antigens.
→ no live components, no risk of inducing
disease DNA VACCINES
→ safer and more stable than LAVs ❑ still experimental.
→ excellent stability profile ❑ developed less than ten years ago.
❑ uses genetically engineered DNA to induce an
SUBUNIT → aka “conjugate vaccines” immunologic response against bacteria, viruses,
VACCINES → biosynthetic vaccines parasites, and potentially cancer.
containing only cellular
fragments of the pathogen ❑ uses a DNA plasmid that encodes for a protein
that originated from the pathogen in which the
FOR: Human papilloma virus (HPV), vaccine will be targeted.
pneumococcal, meningococcal
❑ Administration:
**may be generated by breaking - intramuscular injection (target the myocytes);
open viruses or expressing specific - subcutaneous/intradermal (target the
proteins keratinocytes)

IMMUNE RESPONSE: mRNA VACCINES

✓ must determine which combination of
antigenic properties will produce an effective
immune response with the correct pathway.
✓ Response may be elicited, but with no
guarantee that memory will form (for future
responses)
❑ uses man-made copy of a natural chemical
called messenger RNA (mRNA) to instruct the
body to produce an immune response.
❑ Do NOT ALTER our DNA in any way; never enters
the nucleus of the cell.
❑ the basis of Pfizer, Moderna COVID-19 vaccines

**less strong immune response compared to LAVs

TYPES OF VACCINES
SAFETY AND STABILITY:
→ no live components, no risk of inducing DNA AND RNA
disease HOW IT WORKS - uses DNA or RNA molecules
→ safer and more stable than LAVs to teach the immune system
→ excellent stability profile to target key viral proteins

VECTOR → live microorganisms are ADVANTAGES - easy and quick to design

VACCINES attenuated and modified to
express entire genomes or a
portion of foreign DNA or RNA DISADVANTAGES - never been done before
sequences or proteins. - no licensed DNA or RNA
→ require a nonpathogenic vaccines currently in use
replicative competent vector EXISTING - None
as a recipient or a carrier into EXAMPLES
which the genetic sequence of GROUP TESTING - Moderna (RNA)
interest will be inserted. THIS APPROACH - Inovio (DNA)
FOR COVID-19
FOR: Hepatitis B, Ebola

DNA & MRNA → “Third generation vaccines”

VACCINES

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MLS1-5 / LECTURE / CONTENTS ARE PPT AND LECTURE BASED

EXISTING - Pertussis
LIVE ATTENUATED EXAMPLES - Hepatitis C
HOW IT WORKS - weakened version of the - Human Papillomavirus
actual virus GROUP TESTING - Novavax
THIS APPROACH - AdaptVac
ADVANTAGES - stimulates a robust immune FOR COVID-19
response without causing
serious disease VIRAL VECTOR
HOW IT WORKS - Takes a harmless virus and
DISADVANTAGES - not safe for compromised uses it to deliver viral genes
immune systems to build immunity
EXISTING - Measles
EXAMPLES - Mumps ADVANTAGES - live virus tend to elicit
- Rubella stronger immune response
- Chickenpox that dead viruses or subunit
GROUP TESTING - Codagenix vaccines
THIS APPROACH - Indian Immunologicals Ltd. DISADVANTAGES - important to pick a viral
FOR COVID-19 vector that is truly safe
- an immune response to the
INACTIVATED viral vector could make the
HOW IT WORKS - uses whole virus after it has vaccine less effective
been killed w/ heat or EXISTING - Ebola
chemicals EXAMPLES - Veterinary Medicine
GROUP TESTING - University of Oxford &
ADVANTAGES - safe because virus is already THIS APPROACH AstraZeneca
dead FOR COVID-19 - CanSino Biologics
- easy to make - Johnson & Johnson

DISADVANTAGES - not as effective as a live virus REQUIREMENTS FOR VACCINE DEVELOPMENT

- some have made the disease
worse
- safety for novel coronavirus ✓ Safety (only minimal side effects)
needs to be shown in clinical ✓ Be stable during its shelf life, with potency
trials remaining at proper level.
EXISTING - Polio ✓ Be immunogenic enough to produce a strong
EXAMPLES immune response.
GROUP TESTING - Sinovac ✓ Inexpensive to produce and deliver.
THIS APPROACH - Sinopharm.
FOR COVID-19 **Agency: FDA (Food and Drug Administration)
**researchers test vaccines with adult first
SUBUNIT
HOW IT WORKS - uses a piece of a virus’
surface to focus your STAGES OF VACCINE DEVELOPMENT
immune system on a single
target STAGES
PHASE 1 → 20-100 healthy volunteers
ADVANTAGES - focuses the immune ✓ Is this vaccine safe?
response on the most ✓ Does this vaccine seem to
important part of the virus work?
for protection ✓ Serious side effects?
- cannot cause infection ✓ How is the size of dose
related to side effects?
DISADVANTAGES - may not stimulate a strong
response, other chemicals PHASE 2 → Several hundred volunteers
may need to be added to
boost long-term immunity ✓ What are the most common
short-term side effects?

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MLS1-5 / LECTURE / CONTENTS ARE PPT AND LECTURE BASED

✓ How are the volunteers IMMUNE RESPONSES OF COVID-19 VACCINES

immune systems responding
to the vaccine?
PHASE 3 → hundreds/thousands of volunteers

✓ How do people who get the

vaccine and people who do
not get tha vaccine compre?
✓ Is the vaccine safe?
✓ Effective?
✓ Common side effects?
FDA LICENSES VACCINE ONLY IF:
1. Safe and ffective
2. Benefits outweigh risks

**made in batches called lots

**manufacturers must test all lots to make sure they
are safe, pure and potent.
**can only be released once FDA reviews their safety
and quality
**FDA inspects manufacturing facilities regularly to
ensure quality and safety

HOW VACCINES WORK?

HOW DO VACCINES WORK

✓ induce active immunity by imitating an infection,
it will cause the immune system to produce T-
lymphocytes and antibodies.

✓ induce immunologic memory response: T cells

remain as “memory cells”

vaccination -> adaptive immunity -> flu vaccine ->

memory t-cells & memory b-cells
IMMUNE RESPONSE TO VACCINATION

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MLS1-5 / LECTURE / CONTENTS ARE PPT AND LECTURE BASED

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