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Active                                     Passive
   Killed live or attenuated             Transfer of performed
    organism injected which can            antibodies
    induce immune response
    Long term                            Short term
   Immune system plays role              No role of immune system
   Ex-Hepatitis B vaccine                Ex- diptheria
Diphtheria-pertussis(acellular)-           Hepatitis A &B
    tetanus (DPaT)                         Measles
Inactivated (Salk) polio vaccine           Rabies
    (IPV)
Measles-mumps-rubella (MMR)
    combined vaccine
Haemophilus influenzae (Hib) vaccine
 A vaccine is a biological
preparation that improves
immunity to a particular
disease. A vaccine typically
contains an agent that
resembles a disease-causing
microorganism, and is often
made from weakened or
killed forms of the microbe
or its toxins.
 Vaccine is a form of Active
immunization
   Edward Jenner-The term vaccine derives
    from Edward Jenner’s 1796 use of the term cow
    pox (Latin variolæ vaccinæ, adapted from the
    Latin vaccīn-us, from vacca cow), which, when
    administered to humans, provided them
    protection against smallpox.
   Louis Pasteur- generalized Jenner's idea by
    developing a rabies vaccine, and in the
    nineteenth century vaccines were considered a
    matter of national prestige, and compulsory
    vaccination laws were passed.
The Mechanism
of a Vaccine
 In an ideal
scenario, whenever a
vaccine is first
administered, it is
phagocytized by an
antigen presenting cell
(APC).
 Recent research suggest
that it is particularly
important that the vaccine
be taken up by a dendritic
cell.
 This is because dendritic
cells play a key role in
activating T cells, which
become helper T cells (Th
cells).
  From there, the activated
Th cells goes on to activate
mature B-cells.
 These activated B-cells
divides into two cell
types, antibody-producing
plasma cells and, most
importantly, memory B
cells.
 Memory T-cells are also
established, however, they
usually have a shorter half-
life than memory B
cells, thus, they play only a
minor role in long-term
immunity.
 Usually, there are no
cytotoxic T-cells formed
whenever the body
responds to a vaccine.
Potential
Shortcomings
of Vaccines
 In some rare cases, a
vaccine may directly
activate a B cell, without
stimulation from Th cells.
 Such antigens are
known as T-independent
(TI) antigens.
 The problem with such
a response is that only
Ig-M antibodies are
produced and there are
no memory cells
established.
 Thus, such a vaccine
will be useless against
establishing immunity.
TYPES
Killed

Attenuated

Toxoid

Surface molecule
Recombinant
vector vaccine
DNA Vaccine

Multivalent
subunit Complex
Chimeric vaccine
Killed/Inactivated
Some   vaccines contain
killed, but previously
virulent, micro-organisms that
have been destroyed with
chemicals, heat, radioactivity or
antibiotics.
Examples are the influenza
vaccine, cholera
vaccine, bubonic plague
vaccine, polio vaccine, hepatitis
A vaccine, and rabies vaccine
HEAT                          CHEMICAL
                              INACTIVATED
INACTIVATED
 Heat inactivation is           Chemical inactivation
 generally unsatisfactory       with formaldehyde or
 because it causes              various alkylating
 extensive denaturation         agents has been
 of proteins; thus, any         successful.
 epitopes that depend on        E.g.-Salk Polio vaccine
 higher orders of protein
 structure are likely to be
 altered significantly.
      Microorganisms can be attenuated so that they
    lose their ability to cause significant disease
    (pathogenicity) but retain their capacity for
    transient growth within an inoculated host.
      Attenuation often can be achieved by growing a
    pathogenic bacterium or virus for prolonged
    periods under abnormal culture conditions. This
    procedure selects mutants that are better suited to
    growth in the abnormal culture conditions and are
    therefore less capable of growth in the natural
    host.
pathogenic bacteria and virus   mutants are sel
are grown in abnormal culture   -ected
Toxoid
 Some species of
bacterial produce what
is known as exotoxins.
 Toxoid are vaccines
which consist of
exotoxins that have been
inactivated, either by
heat or chemicals.
 These vaccines are
intended to build an
immunity against the
toxins, but not
necessarily the bacteria
that produce the toxins.
 Some examples are
botulinum antitoxin and
diphtheria antitoxin
Recombinant               Clone the gene for major
vaccines/Surface           surface antigen of hepatitis
molecule                   virus(HBsAg)

                          Express in yeast cell
The  gene encoding
any immunogenic
protein can be            Recombinant yeast cells are
cloned and                 grown in large fermenters
expressed in
bacterial, yeast, or
                          Yeast cell
mammalian cells
using Recombinant
                           harvested, disrupted by
DNA technology             high pressure
Example-
HepatitisB vaccine        Recombinant HBsAg
                           released& purified

                          Produce Ab’s
Recombinant vector
vaccine
Genes  that encode
major antigens of
especially virulent
pathogens can be
introduced into
attenuated viruses or
bacteria.
The attenuated
organism serves as a
vector, replicating
within the host and
expressing the gene
product of the pathogen.
Example -vaccinia
vector vaccine
   DNA vaccines consist of plasmids that contains genes
    for certain types of antigens
   Plasmid DNA encoding antigenic proteins is injected
    directly into the muscle of the recipient.
   Muscle cells take up the DNA and the encoded protein
    antigen is expressed, leading to both a humoral
    antibody response and a cell mediated response
   The fact that muscle cells express low levels of class I
    MHC molecules and do not express costimulatory
    molecules suggests that local dendritic cells maybe
    crucial to the development of antigenic responses to
    DNAvaccines
   Gene gun can also be used for administration
DNA VACCINE                           NON DNA VACCINE
   encoded protein is expressed          Artificial form
    in the host in its natural form
   induce both humoral and               One type of immunity
    cell-mediated immunity                No memory(only in
   cause prolonged expression
    of the antigen, which                  some cases)
    generates significant
    immunological memory.
   Refrigeration is not required         Handling problem
    for the handling and storage
    of the plasmid DNA
   same plasmid vector can be            Can’t be reused
    used for different vaccines
   Synthetic peptide vaccines
   Contain immunodominant B-cell and T-cell
    epitopes.
   Works intra cellularly therefore effective in
    CTL response
   There are number of innovative techniques are
    being applied to develop multivalent vaccines
    that can present multiple copies of a given
    peptide or a mixture of peptides to the immune
    system-:
Solid matrix–antibody
antigen
(SMAA) complexes
 Monoclonal antibodies
are attached to solid
matrix

Saturate the antibody
with desired antigen.

Complex formed can be
used as vaccine

 Induce both HIR and
CMI

 Particulate nature
therefore increased
immunogenicity
facilitating phagocytosis
Detergent
oDetergent  +protein antigen ->1,2,3
oMixing protein and detergent and then
remove detergent from micelle
oThe individual proteins orient
themselves with their hydrophilic
residues toward the aqueous
environment and the hydrophobic
residues at the centre so as to exclude
their interaction with the aqueous
environment.
1.ISCOM-Immunostimulating
complexes (ISCOMs) are lipid carriers
prepared by mixing protein with
detergent and a glycoside called Quil A.
2.Liposome-Liposomes containing
protein antigens are prepared by mixing
the proteins with a suspension
of phospholipids under conditions that
form vesicles bounded by a bilayer.
Examples-influenza
virus
         -measles virus
         -hepatitis B virus
         -HIV
fuse with the plasma
membrane to deliver the
antigen
intracellularly, where it
can be processed by the
cytosolic pathway and
thus induce a cell-
mediated response
   Chimeric vaccines usually consist of attenuated
    viruses that have been engineered to carry
    antigens from multiple types of pathogens.
   For example, the yellow fever vaccine YF17D
    has been engineered to carry antigens from
    HIV, different types of bacteria, malaria, even
    cancer.
   The main adv.of a Chimeric vaccine is the
    establishment of immunity against several
    different diseases with one administration
   There are three main vaccine manufacturing
    strategies:
       In-vivo
       In-vitro
       Chemical Synthesis
   Some vaccines can be produced using any one
    of the three methods while for other
    vaccines, only one method will work.
In-Vivo
In in-vivo
manufacturing, the
vaccine is produced
inside a living organism.
Embryonated Chicken
eggs are commonly
used, particularly in
producing flu vaccines.
Vaccines, such as anti-
idiotype, can also be
produced in lab
animals, such as mice.
There are even some
species of plant, such as
bananas, that have been
genetically engineered to
produce a vaccine.
In-Vitro
 Here, using
recombinant DNA
technology, vaccines can
be produced in yeast
cultures, bacterial
cultures, or cell cultures.
Recombinant
vaccines, such as
chimeric vaccines, are
produced in this manor.
Attenuated
virus/bacteria vaccines
can also be produced
this way.
Chemical
Synthesis
 Here, instead of using
biological systems to
produce a vaccine, a
vaccine can be produced
in a lab.
 Vaccines that utilize
synthetic peptides as
well as conjugated lipids
and polysaccharides are
manufactured this way.
 Usually, this method is
used in combination
with either in-vivo or in-
vitro production.
   The primary risk associated with vaccines, especially
    vaccines that utilize live organisms, is that the vaccine
    itself causes illness.
     This Happened with the orally administered Sabin
       vaccine for polio, where some individuals became ill
       and, in rare cases, even spread the illness to other
       individuals who were not exposed to the vaccine.
   Another risk is that the vaccine may behave as a super
    antigen and over stimulate the immune system.
   Yet a third risk is that some individuals may have an
    allergic reaction to the vaccine, especially vaccines
    produced in Embryonated chicken eggs and in
    transgenic plants.
Active vs Passive Immunization: Understanding the Mechanism and Types of Vaccines

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Active vs Passive Immunization: Understanding the Mechanism and Types of Vaccines

  • 1.
  • 2. Active Passive  Killed live or attenuated  Transfer of performed organism injected which can antibodies induce immune response  Long term  Short term  Immune system plays role  No role of immune system  Ex-Hepatitis B vaccine  Ex- diptheria Diphtheria-pertussis(acellular)- Hepatitis A &B tetanus (DPaT) Measles Inactivated (Salk) polio vaccine Rabies (IPV) Measles-mumps-rubella (MMR) combined vaccine Haemophilus influenzae (Hib) vaccine
  • 3.  A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins.  Vaccine is a form of Active immunization
  • 4. Edward Jenner-The term vaccine derives from Edward Jenner’s 1796 use of the term cow pox (Latin variolæ vaccinæ, adapted from the Latin vaccīn-us, from vacca cow), which, when administered to humans, provided them protection against smallpox.  Louis Pasteur- generalized Jenner's idea by developing a rabies vaccine, and in the nineteenth century vaccines were considered a matter of national prestige, and compulsory vaccination laws were passed.
  • 5. The Mechanism of a Vaccine  In an ideal scenario, whenever a vaccine is first administered, it is phagocytized by an antigen presenting cell (APC).  Recent research suggest that it is particularly important that the vaccine be taken up by a dendritic cell.  This is because dendritic cells play a key role in activating T cells, which become helper T cells (Th cells).
  • 6.  From there, the activated Th cells goes on to activate mature B-cells.  These activated B-cells divides into two cell types, antibody-producing plasma cells and, most importantly, memory B cells.  Memory T-cells are also established, however, they usually have a shorter half- life than memory B cells, thus, they play only a minor role in long-term immunity.  Usually, there are no cytotoxic T-cells formed whenever the body responds to a vaccine.
  • 7. Potential Shortcomings of Vaccines  In some rare cases, a vaccine may directly activate a B cell, without stimulation from Th cells.  Such antigens are known as T-independent (TI) antigens.  The problem with such a response is that only Ig-M antibodies are produced and there are no memory cells established.  Thus, such a vaccine will be useless against establishing immunity.
  • 9. Killed/Inactivated Some vaccines contain killed, but previously virulent, micro-organisms that have been destroyed with chemicals, heat, radioactivity or antibiotics. Examples are the influenza vaccine, cholera vaccine, bubonic plague vaccine, polio vaccine, hepatitis A vaccine, and rabies vaccine
  • 10. HEAT CHEMICAL INACTIVATED INACTIVATED Heat inactivation is Chemical inactivation generally unsatisfactory with formaldehyde or because it causes various alkylating extensive denaturation agents has been of proteins; thus, any successful. epitopes that depend on E.g.-Salk Polio vaccine higher orders of protein structure are likely to be altered significantly.
  • 11. Microorganisms can be attenuated so that they lose their ability to cause significant disease (pathogenicity) but retain their capacity for transient growth within an inoculated host.  Attenuation often can be achieved by growing a pathogenic bacterium or virus for prolonged periods under abnormal culture conditions. This procedure selects mutants that are better suited to growth in the abnormal culture conditions and are therefore less capable of growth in the natural host.
  • 12. pathogenic bacteria and virus mutants are sel are grown in abnormal culture -ected
  • 13. Toxoid  Some species of bacterial produce what is known as exotoxins.  Toxoid are vaccines which consist of exotoxins that have been inactivated, either by heat or chemicals.  These vaccines are intended to build an immunity against the toxins, but not necessarily the bacteria that produce the toxins.  Some examples are botulinum antitoxin and diphtheria antitoxin
  • 14. Recombinant  Clone the gene for major vaccines/Surface surface antigen of hepatitis molecule virus(HBsAg)  Express in yeast cell The gene encoding any immunogenic protein can be  Recombinant yeast cells are cloned and grown in large fermenters expressed in bacterial, yeast, or  Yeast cell mammalian cells using Recombinant harvested, disrupted by DNA technology high pressure Example- HepatitisB vaccine  Recombinant HBsAg released& purified  Produce Ab’s
  • 15. Recombinant vector vaccine Genes that encode major antigens of especially virulent pathogens can be introduced into attenuated viruses or bacteria. The attenuated organism serves as a vector, replicating within the host and expressing the gene product of the pathogen. Example -vaccinia vector vaccine
  • 16. DNA vaccines consist of plasmids that contains genes for certain types of antigens  Plasmid DNA encoding antigenic proteins is injected directly into the muscle of the recipient.  Muscle cells take up the DNA and the encoded protein antigen is expressed, leading to both a humoral antibody response and a cell mediated response  The fact that muscle cells express low levels of class I MHC molecules and do not express costimulatory molecules suggests that local dendritic cells maybe crucial to the development of antigenic responses to DNAvaccines  Gene gun can also be used for administration
  • 17.
  • 18. DNA VACCINE NON DNA VACCINE  encoded protein is expressed  Artificial form in the host in its natural form  induce both humoral and  One type of immunity cell-mediated immunity  No memory(only in  cause prolonged expression of the antigen, which some cases) generates significant immunological memory.  Refrigeration is not required  Handling problem for the handling and storage of the plasmid DNA  same plasmid vector can be  Can’t be reused used for different vaccines
  • 19. Synthetic peptide vaccines  Contain immunodominant B-cell and T-cell epitopes.  Works intra cellularly therefore effective in CTL response  There are number of innovative techniques are being applied to develop multivalent vaccines that can present multiple copies of a given peptide or a mixture of peptides to the immune system-:
  • 20. Solid matrix–antibody antigen (SMAA) complexes  Monoclonal antibodies are attached to solid matrix Saturate the antibody with desired antigen. Complex formed can be used as vaccine  Induce both HIR and CMI  Particulate nature therefore increased immunogenicity facilitating phagocytosis
  • 21. Detergent oDetergent +protein antigen ->1,2,3 oMixing protein and detergent and then remove detergent from micelle oThe individual proteins orient themselves with their hydrophilic residues toward the aqueous environment and the hydrophobic residues at the centre so as to exclude their interaction with the aqueous environment. 1.ISCOM-Immunostimulating complexes (ISCOMs) are lipid carriers prepared by mixing protein with detergent and a glycoside called Quil A. 2.Liposome-Liposomes containing protein antigens are prepared by mixing the proteins with a suspension of phospholipids under conditions that form vesicles bounded by a bilayer.
  • 22. Examples-influenza virus -measles virus -hepatitis B virus -HIV fuse with the plasma membrane to deliver the antigen intracellularly, where it can be processed by the cytosolic pathway and thus induce a cell- mediated response
  • 23. Chimeric vaccines usually consist of attenuated viruses that have been engineered to carry antigens from multiple types of pathogens.  For example, the yellow fever vaccine YF17D has been engineered to carry antigens from HIV, different types of bacteria, malaria, even cancer.  The main adv.of a Chimeric vaccine is the establishment of immunity against several different diseases with one administration
  • 24. There are three main vaccine manufacturing strategies:  In-vivo  In-vitro  Chemical Synthesis  Some vaccines can be produced using any one of the three methods while for other vaccines, only one method will work.
  • 25. In-Vivo In in-vivo manufacturing, the vaccine is produced inside a living organism. Embryonated Chicken eggs are commonly used, particularly in producing flu vaccines. Vaccines, such as anti- idiotype, can also be produced in lab animals, such as mice. There are even some species of plant, such as bananas, that have been genetically engineered to produce a vaccine.
  • 26. In-Vitro  Here, using recombinant DNA technology, vaccines can be produced in yeast cultures, bacterial cultures, or cell cultures. Recombinant vaccines, such as chimeric vaccines, are produced in this manor. Attenuated virus/bacteria vaccines can also be produced this way.
  • 27. Chemical Synthesis  Here, instead of using biological systems to produce a vaccine, a vaccine can be produced in a lab.  Vaccines that utilize synthetic peptides as well as conjugated lipids and polysaccharides are manufactured this way.  Usually, this method is used in combination with either in-vivo or in- vitro production.
  • 28. The primary risk associated with vaccines, especially vaccines that utilize live organisms, is that the vaccine itself causes illness.  This Happened with the orally administered Sabin vaccine for polio, where some individuals became ill and, in rare cases, even spread the illness to other individuals who were not exposed to the vaccine.  Another risk is that the vaccine may behave as a super antigen and over stimulate the immune system.  Yet a third risk is that some individuals may have an allergic reaction to the vaccine, especially vaccines produced in Embryonated chicken eggs and in transgenic plants.