Vaccine immunology m.fathy

Vaccine Immunology
By
Mohamed Fathy , B.V.Sc
Virology Pre-Master Student
E-mail : mohfathy.vet@hotmail.com

Active Immunity
• Antibody mediated
– B cells
• Cell mediated
– T cells
Cytotoxic (destroy infected cells and viruses)
Helper (stimulate and direct activity of B cells)

What is Antigen ?
A live or inactivated substance (e.g. protein or
polysaccharide) capable of producing an
immune response .

What are Antibodies ?
Produced by B cells to help eliminate an antigen
• Different types
• IgM, IgG, IgA, IgD, IgE
• Functions :
Neutralize toxins
Block adhesion/cell entry of the antigen
Neutralize and prevent viral replication
• Antigen specificity :
Cannot cross-protect different types of micro-
organism

Immune response following exposure
to antigen
Primary response
• rapid
• mainly IgM
Secondary response
• faster and more
powerful
• mainly IgG

-It aims to protect the host from disease upon exposure to
noxious microorganisms .
-It can be achieved successfully if the host generated
available immune effector elements such as :
Antibodies .
- Antibodies are able to immediately recognize and
neutralize this pathogen .
Avian Immunology , Fred Davison P 374
What is the Aim of Vaccination ?

How do vaccines mediate protection?
• Long-term immunity is conferred by the
maintenance of antigen-specific immune
effectors and/or by the induction of immune
memory cells that can rapidly reactivated into
immune effectors in case of next pathogen
exposure.

The main effectors of vaccine
responses
• The nature of the vaccine exerts a direct
influence on the type of immune effectors
that are predominantly elicited and mediate
protective efficacy .

Effector Mechanisms Triggered by Vaccines
Antibodies prevent or reduce infections by extra-
and intracellular agents and clear extracellular
pathogens through :
 Binding to the enzymatic active sites of toxins or
preventing their diffusion
 Neutralizing viral replication, e.g. preventing viral
binding and entry into cells
 Promoting opsonophagocytosis of extracellular
bacteria, i.e. enhancing clearance by
macrophages and neutrophils
 Activating the complement cascade

CD8+ T cells do not prevent but reduce, control
and clear intracellular pathogens by:
• Directly killing infected cells (release of
perforin, granzyme, etc.)
• Indirectly killing infected cells through
antimicrobial cytokine release

CD4+ T cells do not prevent but participate to
the reduction, control and clearance of extra-
and intracellular pathogens by :
• Producing IFN-γ, TNF-α/-β, IL-2 and IL-3 and
supporting activation and differentiation of B
cells, CD8+T cells and macrophages.(Th1 cells )
• Producing IL-4, IL-5, IL-13, IL-6 and IL-10 and
supporting B cell activation and differentiation
(Th2 cells)

Initiation of Vaccine Response
World Health Organization WHO , Vaccine Immunology ,
http://www.who.int/immunization/documents/Elsevier_Vaccine_immunology.pdf

Recognition of Vaccine Determinants by Pattern
Recognition Receptors
LigandsReceptors
Certain bacterial lipoproteinsTLR1
Peptidoglycan, lipoproteins, glycolipids, lipopolysaccharideTLR2
Viral double-stranded RNATLR3
Bacterial lipopolysaccharidesTLR4
TLR5
Bacterial flagellinsTLR6
Lipotechoic acid, lipopeptidesTLR7
Single-stranded RNATLR8
TLR9
Single-stranded RNATLR10
CpG olignucleotides Unknown PeptidoglycansNOD1 , NOD2

Determinants of Primary Vaccine Antibody Responses
in Healthy Individuals
MechanismDeterminant
Higher intensity of innate responses, higher antigen
content following replication and more prolonged antigen
persistence generally result into higher Ab responses to
live than inactivated vaccines.
Vaccine type
Live vs inactivated.
Recruitment of T cell help and induction of GCs results
into higher Ab responses to protein than to PS vaccines.
Protein vs polysaccharide
Modulation of antigen delivery and persistence (depot or
slow-release formulations) or enhancement of Th
responses (immunomodulator) may support or limit Ab
responses
Adjuvants

Failure to induce GCs limit immunogenicity.Antigen nature
Polysaccharide antigens
Inclusion of epitopes readily recognized by B cells,
inclusion of epitopes readily recognized
by follicular helper T cells, elicitation of efficient follicular
T cell help and the capacity of antigen to associate/
persist in association to FDCs result into higher Ab
responses.
Protein antigens
higher Ag doses increase the availability of Ag for B / T
cell binding and activation, as well as for
association with FDCs
Antigen dose

A 3 week minimal interval between primary doses avoids
competition between successive waves of primary
responses.
Vaccine schedule
Interval between doses.
.
Gene polymorphisms in molecules
critical for B and T cell activation/differentiation are
likely to affect Ab responses
Genetic determinants
Mostly yet identifiedEnvironmental factors
Early life immune immaturity .Age at immunization

Types of viral Vaccines
1- Live attenuated vaccine (MLV).
2- Inactivated vaccines (Killed).
3- Molecular-Based Vaccines

Live attenuated vaccine (MLV).
A-Naturally occurring virus used as vaccines
(e.g. Lentogenic strain of NDV).
B- Immunologically related virus from different
species “Heterotypic vaccines” (e.g. Turkey
herpes virus against Marek’s disease virus,
Sheep pox against LSD in cattle).
C- Attenuated vaccines: Attenuation is usually
achieved by passage of the virus in foreign
host such as ECE or tissue culture cells.
Reference : Prof.Dr.M.Shalaby Lecture2005

Advantages of Live Vaccines
1- Activates all phases of immune system can get
humoral IgG and local IgA.
2- Raises immune response to all protective antigens,
inactivation by formaldhyde may alter antigenicity.
3- Induction of interferons.
4- Low cost.
5- Quick immunity in majority of vaccines.
6- Easily administrated by all routes.
7- Easy transport in field.
8- Can lead to elimination of wild type virus from the
community.

Disadvantaged of live vaccines
1- Mutation, reversion to virulence (Major disadvantage).
2- Spread to contacts of vaccines who have not
vaccinated.
3- Spread vaccine not standardized-may be mutated.
4- Poor uptake in tropical areas.
Reference : Prof.Dr.M.Shalaby Lecture 2005

Inactivated vaccines (Killed).
• Made from virulent virus by eliminating its infectivity
and retaining its immunogenicity.
• Inactivating agents :
most commonly used are :
1- B-propiolactone
2- Formaldehyde
3- Ethylenimine and azuridine

Advantages of Killed Vaccines
1- Gives sufficient humoral immunity if boosters
given.
2- No mutation of reversion ( A big advantage).
3- Safe for pregnant animals.
4- Better to be applied in tropical countries.
Ref : Prof.Dr.M.Shalaby Lecture 2005

Disadvantages of killed vaccines
1- Booster doses are needed (Short immunity).
2- No local immunity.
3- Administration only by injection.
4- Adjuvants is essential to provoke cell
mediated immunity.

Live attenuated Vs Killed Vaccine
Inactivated vaccinesLiving vaccines
1-Stable on storage
2-Unlikely to cause disease
through residual
virulence.
3-Unlikely to contain live
contaminating organisms.
1-Few inoculating doses
required.
2-Adjuvants unnecessary
3-Less chance of
hypersensitivity.
4-Induction of interferon.
5-Relatively cheap.

Molecualr Based Vaccines
• Acc .to USDA classification of Genetically Engineered
Veterinary Biologics:
Category I: Vaccines that contain inactivated
recombinant organisms or purified antigens derived
from recombinant organisms.
Category II: Vaccines containing live organisms that
contain gene deletion or heterologous marker genes.
Category III: Vaccines that contain live expression
vectors containing heterologous genes for immunizing
antigens or other immune stimulants.

Novel Molecular Based Vaccines
• Examples of Novel molecular based vaccines
in veterinary Field :
1- VP1 Protective antigen of FMDV
2- VP2 of IBDV
4- H5 Gene of Avian influenza virus
3- Thymidine Kinase TK Gene of Pseudorabies
virus in swine .

Vaccine Safety vs Efficacy
Safety
Efficacy

Recombinant HVT+ IBD Vaccine
MERIAL Scientific Data

Ideal Vaccine Characterstics
1- Produce effective resistance to infection in vaccinated
animal or bird.
2- Have long lasting resistance (stabilizers and/or heat
resistant mutants).
3- Safe for vaccinated animals ( no reversion to virulence).
4- Should be pure from other adventitious viruses (e.g.
BVD).
5- Sterile from bacteria, fungal and mycoplasma
contamination.
6- Stable.
7- Reasonably cheap to produce.

• Give life-long immunity
• Broadly protective
against all variants of
organism
• Prevent disease
transmission
• Rapidly induce
immunity
• Effective in all subjects
(the old & very young)

• Transmit maternal
protection to the foetus
• Require few
immunizations to induce
protection
• Not need to be
administered by
injection (oral,
intranasal,
transcutaneous)
• Stable, cheap & safe

Vaccine Assessment
• Efficacy of a vaccine is called preventable fraction.
% of controls dying - % of vaccinated dying
PF =
% of controls dying
• Good effective vaccines should have a PF of at
least 80%, Obviously less effective vaccines are
acceptable if no better is available.

Other Vaccine components
• Conjugating agents :
Carrier proteins which combine with antigens to
improve immunogenicity
• Suspension fluid :
Fluid (water, saline, tissue-culture mixture)
• Preservatives, stabilizers, antimicrobial agents
– Trace amounts used to stabilize vaccine
– May cause allergic reaction

• Adjuvants :
Aluminium salt used to increase
immunogenicity of vaccines containing
inactivated micro-organisms or their products.

Thiomersal
– Used in vaccine production since the 1930s
– Mercury containing compound used in some
vaccines to prevent bacterial and fungal
growth.
– Also used as inactivating agent in early stage
of production of some killed vaccines
– In 1999 EU and U.S. manufacturer’s decision
to decrease thiomersal levels in vaccines

Routes of Vaccination
• S/C and I/M Routes
• Intranasal ------ Mucosal immunity
• Eye drops , drinking water ( Poultry )

Vaccination Timing
1- Varies according to the species of animal and whether
a live or inactivated vaccine is used. It is most
important to bypass the maternal immunity
2- Activity of passive antibodies is determined by the
level of Abs in the dam, how much is transferred via
colostrum and its capacity to neutralize the vaccine.
Passive antibodies wanes because circulating IgG has a
half life of 10-20 days in domestic animals and 2-4 days
in poultry.
3- Action of passive immunity may be avoided by given
vaccines via the respiratory tract.
4- Increasing passive immunity may be a deliberate part
of the control program, thus neonatal diarrhea might
be reduced by vaccinating the dams.

Vaccination Failure
• Disease induced by strains of organisms or
antigens that differ from the strain in the
vaccine you used
• Faulty production of specific lot of vaccine
(not enough antigen; accidental inactivation
during manufacture)
• Unsatisfactory storage, exposure to heat
(keeping it in the cab of a truck during the
height of summer), freezing (esp. modified
live vaccines)
Reference : Prof.Dr.M.Shalaby Lecture 2005

Vaccination Failure
• Administration by unconventional routes (e.g.,
given intranasal vaccine intramuscularly, or
vice versa)
• Animals incubating disease at time of
vaccination
• Disease due to an agent other than the one in
the vaccine
• Blocking effects of maternal antibodies eg.,
IBD Vaccination.

Vaccination Failure
• Administration of antibiotics in conjunction
with live bacterial vaccines.
• Chemical sterilization of syringes
• Immune response is suppressed (heavily
parasitized or malnourished animals; stress of
pregnancy, extremes of cold and heat, and
fatigue)

Other Refernces
• http://www.cdc.gov/vaccines/pubs/pinkbook/
downloads/prinvac.pdf
• MERIAL , Internal scientific data , Vaxxitek

Vaccine immunology m.fathy

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Viewers also liked

Viewers also liked (20)

Similar to Vaccine immunology m.fathy

Similar to Vaccine immunology m.fathy (20)

Recently uploaded

Recently uploaded (20)

Vaccine immunology m.fathy