Introduction to Vaccinology and Vaccines.pptx

INTRODUCTION TO VACCINOLOGY AND
VACCINES
ANDREW MUSYOKI
[MSc, PhD (Med) Virology]
Department of Microbiological Pathology, School of Medicine
South African Vaccination and Immunisation Centre (SAVIC)
Sefako Makgatho Health Sciences University (SMU)

2
Presentation outline
 The need for a defense system:
Microorganisms
 How the human immune system works
 Vaccination and how vaccines work
 Types of vaccines

MICROORGANISMS: Bacteria and Viruses

MICROORGANISMS …
 True pathogens overcome defenses
 Invade tissues
 Cause disease
 Clinical symptoms
 host versus invader
 damage directly caused by
pathogen
 Colonize / be carried without
causing illness

CHARACTERISTICS OF INFECTIOUS DISEASES

HOW THE
HUMAN
IMMUNE
SYSTEM WORKS
https://www.youtube.com/watch?v=zQGOcOUBi6s

SUMMARY OF SPECIFIC IMMUNE RESPONSE
8

SPECIFIC IMMUNE RESPONSE MEMORY
11

VACCINATION AND HOW VACCINES
WORK
12

VACCINES AND VACCINATION
13
• A vaccine is a preparation/suspension of live, weakened, killed, or fragmented
microorganisms, or toxin/proteins from a pathogenic microorganism, that is given to
stimulate the body's immune response against infection by the disease-causing
• Given by injection, by mouth or as a nasal spray.
• Vaccination is a simple, safe, and effective way of administering a vaccine for
protection against harmful diseases before anyone encounters the disease-causing
organism.
•When you get a vaccine, your immune system responds/should respond.
• Therefore, the two key reasons to get vaccinated are to protect ourselves and to
protect those around us.

IMMUNIZATION
14
 Immunization refers to the process of both getting the vaccine which then triggers
your immune system to respond and becoming immune to the disease following
vaccination. When one gets a vaccine, the following happens:
 Body’s immune system recognizes the active vaccine component (bacterial or
viral)
 Produces antibodies naturally to fight the virus/bacteria.
 Remembers the germ and how to fight it and if exposed to the germ in future,
the immune system can quickly destroy it before the host becomes unwell.
Adaptive immune systems are designed to remember.
 Rather than treating a disease after it occurs, vaccines protect us from getting sick
with the disease in the first instance.
 Vaccination/Immunization used interchangeably in common language.

• 20th century's most successful
and cost effective public health
‐
tool for preventing disease and
death
• For people of all ages
– Newborns to the elderly
• Timely immunisation is one of the
most important ways for people to
protect themselves and others from
serious diseases.
VACCINATION
15

16
IMPORTANCE OF VACCINATION
Prevention of morbidity and mortality
Personal immunity
• Reduced risk of infection and disease severity
Population immunity (herd immunity)
• Herd immunity = indirect protection when immunity develops in a population either
through vaccination or through previous infection
• Prevent ongoing transmission
• Protect those who cannot be vaccinated
 Too young to be vaccinated
 Health condition precluding vaccination

VACCINATION: MECHANISMS OF ACTION
17

• Highly immunogenic, inducing a rapid, strong and specific immune response
• Totally effective in a single dose ; Safe: no adverse reactions or side effects
• Induces life-long immunity in 100% of the population
• Stable under non-stringent storage conditions
• Genetically stable (re: live vaccines)
• Easily administered
• Affordable
THE “IDEAL” VACCINE
19

In reality, no vaccine is the “ideal” vaccine
• Most are highly immunogenic
• All vaccines have minimal side effects
• Most are only 80% ‐ 95% effective
• Oral vaccines / nasal spray vaccines are easy to administer; injected vaccines
need expertise
• Lifelong protection usually requires boosters
• Most require stringent storage conditions
• Live vaccines can revert to virulence (polio)
• Traditional vaccines are cheap; newer vaccines are very expensive
“REAL” VACCINES
20

HOW DO VACCINES WORK?
21
https://www.nature.com/articles/s41577-020-00479-7

A BRIEF HISTORY OF VACCINES
Not to scale
smallpox
Smallpox vaccine
(Jenner)
1796
Diphtheria
antitoxin (Roux &
Yersin)
1890
Polio vaccine
(Salk)
1952
Measles (Enders
& co)
1963
Influenza (Salk &
Francis)
1983
Varicella
(Takahashi)
1988
Human
papillomavirus
(Frazer & Zhou)
2006
1721 1885 1921 1956 1977 1985 2003 2020-2021
Variolation Rabies Tuberculosis, Polio vaccine Haemophilus Hepatitis B Ebola rVSV- SARS-CoV-2
introduced in (Pasteur) BCG (Calmette (Sabin) influenzae type (Blumberg) ZEBOV (Various)
England to & Guérin) b (Smith &
prevent Anderson)
Live attenuated, inactivated, toxoid, conjugate, recombinant, viral vector, mRNA

Types
of
vaccin
es
7
Whole-cell
inactivated
• Killed form of
pathogen
Live
attenuated
• Weakened but
live form of
pathogen
Viral
vector
• Harmless virus to
deliver genetic
material
• Piece of the
pathogen
Subunit
• Small piece of
the virus's
genetic material
RNA
Toxoid
• Modified form of
bacterial toxin
Recombinant
• Genetically
engineered
antigen /
proteins

LIVE, ATTENUATED VACCINES
• Virus or bacteria 'weakened'
• Culturing microorganisms and passaging it through non-human cells,
eggs or animals
• Small dose administered, organism replicates and stimulates immune
response
• Usually do not cause disease, or only mild disease
• Immune response very similar to natural infection
• Could be dangerous in immune compromised individuals
• Could revert to original form (e.g. oral polio vaccine)
• Examples: measles, mumps, rubella (MMR), varicella, rotavirus, and
influenza (intranasal), typhoid vaccine (Ty21a), and Bacille Calmette-Guerin
(BCG) 8
Image credit: WHO

INACTIVATED VACCINES
• Not alive, cannot replicate or cause disease
• Need more doses over time and protection does not last as long
• First dose usually only a primer for immune system
• Mostly produces antibody response and not cellular – requires boosters
• Includes whole-cell inactivated vaccines, subunit vaccines, and recombinant
vaccines
9

WHOLE-CELL INACTIVATED VACCINES
• Bacteria or viruses that have been killed or inactivated
• Uses heat, chemicals or radiation
• Cannot replicate or cause disease
• Examples: polio, hepatitis A, rabies, pertussis whole cell vaccine
10
Image credit: WHO

TOXOID VACCINES
• Some bacteria (e.g., tetanus, diphtheria) cause disease by producing toxins
• The ability of the immune system to recognize and eliminate these toxins
provides protection from the disease
• Toxoid vaccines uses inactivated toxins produced by bacteria
• Toxins inactivated using heat or chemicals (e.g. formaldehyde)
• Toxin rendered harmless, but can still stimulate immune system
11

SUBUNIT VACCINES
• Contain a portion of the bacteria or virus needed to produce a protective immune response
• Can be protein, polysaccharide, or a combination of polysaccharide and protein
molecule (i.e., conjugate vaccine)
• The immune response to a pure polysaccharide vaccine is typically T-cell-independent, which
means these vaccines can stimulate B-cells without the assistance of T-helper cells
• T-cell-independent antigens, including polysaccharide vaccines, are not consistently
immunogenic in children younger than age 2 years, probably because of immaturity of the
immune system
• Attaching (conjugating) the polysaccharide antigen to a protein makes it possible to
prevent bacterial infections in populations where a polysaccharide vaccine is not
effective or provides only temporary protection
• Conjugate subunit vaccines produced by chemically attaching a polysaccharide from the
surface of bacteria to a protein molecule (conjugation)
• Example Haemophilus influenzae type b and pneumococcal conjugate vaccines
• Produces long-lasting protective immunity to the polysaccharide antigen
12
Image credit: WHO

RECOMBINANT VACCINES
• Produced by recombinant DNA technology
• Enables the combination of DNA from two or more sources
• Hepatitis B, human papillomavirus (HPV), and influenza (Flublok brand)
vaccines are produced by inserting a segment of the respective viral gene into
the gene of a yeast cell or virus
• The modified yeast cell or virus produces pure hepatitis B surface
antigen, HPV capsid protein, or influenza hemagglutinin when it grows,
which stimulates the immune system
• Serogroup B meningococcal vaccines are proteins and outer membrane
vesicles generated by recombinant technology
13
Image credit: WHO (adapted)

VIRAL VECTOR
• A 'hollowed' out virus is used to package genetic material
from the pathogen into the body
• The viral vector infects cells, delivers genetic material
• Genetic material is translated to the pathogen protein, which
stimulates an immune response
• Examples:
• rVSV-ZEBOV Ebola vaccine is a recombinant vesicular stomatitis
virus including a gene from the Ebola virus
• SARS-CoV-2 adenovirus vaccine is an adenovirus containing
the mRNA for coding a coronavirus spike protein
3
2
Image credit: WHO

mRNA VACCINES
• mRNA enveloped in a lipid (fat) sphere
• The body’s immune cells take up the vaccine particles and reveal the mRNA
• The mRNA gives the cell code to create a protein similar to a protein on
the pathogen's surface
• The immune cell then releases that protein to other immune cells, triggering
an immune response that includes antibody production and activation of
specialized cells to find and kill the pathogen bearing that protein and any
host cells infected
• Example: SARS-CoV-2 mRNA vaccine carries the code to create a protein
similar to the spike protein on the coronavirus’ surface
3
3
Image credit: WHO

Live vaccines Non-live vaccines
BCG DTap and Tdap
Oral polio Haemophilus influenza type b
Rotavirus Inactivated polio
Measles (or MMR) Hepatitis B
Varicella Pneumococcal (conjugate and polysaccharide)
Zoster Hepatitis A
Yellow fever Influenzas
Intranasal influenza Typhoid VI
Oral typhoid Ty21a
34

EPI-SA vaccines
36
+ Birth dose
HepB in HBsAg+
Tdap
MR
PCV10

Vaccine preventable diseases and Herd protection threshold
37

WHY ARE THERE DIFFERENT TYPES?
• Type of pathogen, structure, replication cycle, immune response after natural
infection
• Vaccine safety
• Immunogenicity
• Manufacturing (ease and cost)
• Regulatory approval
3
8

WHICH
PATHOGENS TO
TARGET FOR
VACCINE
DEVELOPMENT
• Disease burden
• Transmission and risk factors
• Feasibility of control measures
• Scientific and technical feasibility
• Economic and market
considerations 3
9

Vaccine
components
• Antigen
• Adjuvants
• Preservatives
• Stabilizers
• Antibiotic
4
0

Vaccine components
• Antigen
• The part of the vaccine that triggers an immune response
• Specific to type of vaccine
• Adjuvants
• Substances added to some vaccines to enhance the body's immune response
to the antigen
• Preservatives
• Certain vaccines, particularly those stored in multi-dose vials, contain
preservatives to prevent the growth of bacteria or other contaminants
• Examples thiomersal, formaldehyde, phenol derivatives
4
1

Vaccine components
• Stabilizers
• Substances that help to maintain the stability and potency of the vaccine
during storage and transportation e.g. maintain pH, prevent hydrolysis or
aggregation
• Examples: magnesium chloride, magnesium sulphate, lactose-sorbitiol,
sorbitol-gelatin, human serum albumin, potassium phosphate
• Antibiotic
• Trace amounts used during manufacturing process to prevent
contamination
• Example neomycin (no penicillins, cephalosporins or sulfonamides)
4
2

Vaccine components: Adjuvants
• Aluminum salts
• Cause local reaction at the injection site, resulting in the release of cytokines,
which are signaling molecules that help to activate the immune system, leads
to an increase in the production of immune cells, such as T cells and B cells,
which are essential for generating an immune response
• Example aluminum hydroxide and aluminum phosphate
• Liposomes
• Tiny spheres made of lipid molecules that can be filled with vaccine antigens
• Deliver antigens, stimulate immune cells (composed of lipid molecules that
are similar to those found in the membranes of some pathogens), activate
immune signaling pathways
4
3

Vaccine components: Adjuvants
• Oil-in-water emulsions
• Can help to stimulate both the innate and adaptive immune responses to the
vaccine
• Pathogen-associated molecular patterns (PAMPs)
• Are naturally present in certain microorganisms and can stimulate the
immune system
• Some adjuvants, such as monophosphoryl lipid A (MPL), are derived
from
PAMPs and can enhance the immune response to the vaccine
4
4

45
SUMMARY: AIM OF VACCINATION

46
TRADITIONAL VACCINES
 Vaccines traditionally made from:
• whole killed or weakened organisms
• antigens that elicit an immune
response
 Antigens are produced in a
laboratory, i.e. outside of the host
 Purified and packaged during the
manufacturing process
 Antigens administered as a vaccine
https://microbenotes.com/vaccines-introduction-and-types/

NEWER VACCINE PLATFORMS
47
https://www.bloomberg.com/news/articles/2021-07-15/mrna-
vaccine-access-carves-up-world-into-haves-and-have-nots
mRNA vaccines Vector based vaccines

Foundation for rapid COVID-19 vaccine development
Coronavirus virology DNA/RNA transfection biology RSV immunology (VAERD)
HIV-driven technology; clinical and research infrastructure development
RSV structure-based vaccine design
Prototype pathogen pandemic preparedness concepts
Nucleic acid vaccine development
CoV spike structure and stabilization Paramyxovirus vaccine antigen design
Public-private partnerships for pandemic response
Advances in human mAb discovery
Advances in HIV Env structure
Advances in platform manufacturing
Advances in protein engineering
Repeated inadequate responses to pandemic threats
Development of prototype mRNA vaccines for MERS-CoV and Nipah
Vaccine development for SARS-CoV-2
40
15
20
3
8
Year(s)
1

CONCLUSIONS
• Vaccines have saved millions of lives
• Vaccinators must know:
• the different types of vaccines
• how vaccines are made
• how they prevent disease in the human body
• how to administer them to patients: each vaccine is
unique
• % population vaccinated for herd immunity
• value of herd immunity for population protection
42
DO
NOT HESITATE,
VACCINATE

Thank you
Visit: http://www.savic.ac.za/
Twitter: @SAVICinfo
Facebook: SAVICinfo

References
• Bonani P, Santos JI (2011). Vaccine evolution. In: Understanding modern vaccines: perspectives in vaccinology.
Elsevier.
• Centers for Disease Prevention and Control (2015). Vaccines and immunizations: Epidemiology and Prevention of
Vaccine-Preventable Diseases. The Pink Book – 13th Edition. Available at
http://www.cdc.gov/vaccines/pubs/pinkbook/index.html
• Plotkin S. History of vaccination. Proc Natl Acad Sci U S A. 2014;111(34):12283-7.
• United States Agency for International Development (2009). Immunization Essentials: A practical field guide.
Available at: http://pdf.usaid.gov/pdf_docs/PNACU960.pdf
• De Cock KM, Simone PM, Davison V, Slutsker L (2013). The new global health. Emerg Infect Dis. 19(8):1192-7.
• Gundling K (2011). Your Immune system 101: Introduction to clinical immunology. University of California
Television. 2011. Available at: https://www.youtube.com/watch?v=_oI0jVN4TTI
• Leo O, Cunningham A, Stern PL. Vaccine immunology. In: Understanding modern vaccines: perspectives in
vaccinology. 2011; Elsevier.
• Kumar V, Abbas AK, Fausto N, Mitchell RN. Chapter 5: Diseases of the immune system. In: Robbins Basic
Pathology, 8th edition. Saunders Elsevier; 2007. p107-172
• NIAID (2014). Overview of the immune system. Available at
https://www.niaid.nih.gov/research/immune- system-overview
• NIAID (2014). Features of an immune response. Available at
https://www.niaid.nih.gov/research/immune-response-features
• NIAID (2014). Immune cells. Available at https://www.niaid.nih.gov/research/immune-cells
• NIAID (2014). Immune tolerance. Available at https://www.niaid.nih.gov/research/immune-tolerance

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