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UNIVERSITY OF THE PHILIPPINES MANILA

COLLEGE OF ARTS AND SCIENCES


DEPARTMENT OF BIOLOGY

BIOLOGY 120 (General Microbiology)


Lecture 2.3c Vaccines
By:
Lani Manahan-Suyom, MSc
SS AY 2013-2014

History
o Edward Jenner (1796)
First to experiment on immunity (smallpox)
Vaccination: treatment or preventive
procedure developed
o Pasteur (1880)
Discovered why vaccination works (cholera)
Lost the ability to cause disease (avirulent);
later used as vaccines
Overview of Active immunization
o Active immunization - administration of antigen
resulting in production of a specific immune
response with immunologic memory. Response
may be cellular or humoral or both.
o Natural immunity - to diseases you have caught
and successfully fought
o Artificial immunity Vaccination(vaccines)
Attributes of a good vaccine
o Ability to elicit the appropriate immune response
for the particular pathogen
o Long term protection ideally life-long
o Safety vaccine itself should not cause disease
o Stable retain immunogenicity, despite adverse
storage conditions prior to administration
o In-expensive
LIVE VACCINES
o Live attenuated organism
o Heterologous vaccines
o Live recombinant vaccines
Live attenuated organism
o Organisms whose virulence has been artificially
reduced by in vitro Culture under adverse
conditions, such as reduced temperature.
Advantages of Attenuated Vaccines 2-1
o Both cell mediated immunity and antibody
response
o Activates all phases of immune system. Can get
humoral IgG and local IgA
o Raises immune response to all protective
antigens. Inactivation may alter antigenicity.
o More durable immunity; more cross-reactive
o Immunity is long lived
o Single dose
Advantages of Attenuated Vaccines 2-2
o Low cost
o Quick immunity in majority of vaccines
o In case of polio and adeno vaccines, easy
administration
o Easy transport in field
o Can lead to elimination of wild type virus from
the community

Disadvantages of Live Attenuated Vaccine


o Mutation; reversion to virulence (often frequent)
o Spread to contacts of vaccine who have not
consented to be vaccinated (could also be an
advantage in communities where vaccination is
not 100%)
o Spread vaccine not standardized--may be backmutated
o Poor "take" in tropics
o Problem in immunodeficiency disease (may
spread to these patients)
Heterologous vaccines
o Closely related organism of lesser virulence,
which shares many antigens with the virulent
organism. The vaccine strain replication in the
host and induces an immune response that cross
reacts with antigens of the virulent organism.
o Vaccinia virus /cowpox virus--- Variola virus
Live recombinant
o Vector
Bovine vaccine
BCG
Killed vaccines
o The organism is propagated in bulk, in vitro, and
inactivated with either beta-propiolactone or
formaldehyde. These vaccines are not infectious
and are therefore relatively safe. However, they
are usually of lower immunogenicity and multiple
doses may be needed to induce immunity. In
addition, they are usually expensive to prepare.
o Inactivated organism: rabies virus; epidmic type
B encephalitis virus.
o Subunit Vaccines: Influenza virus (HA and NA)
o Recombinant proteins: HBV
Advantages of inactivated vaccines
o Gives sufficient humoral immunity if boosters
given
o No mutation or reversion
o Can be used with immuno-deficient patients
o These vaccines tend to be able to withstand
more adverse storage conditions, Sometimes
better in tropics
Disadvantages of inactivated vaccines
o Many vaccines do not raise immunity
o Poor, only antibody, no cell immediate immune
response
o Response is short-lived and multiple doses are
needed
o Inactivated, therefore can not replicate in the
host and cause disease
o Failure in inactivation and immunization with
virulent virus
o Expense: Expensive to prepare

New Methods
o Selection of attenuated virus strain
Varicella
Hepatitis A
o Use monoclonal antibodies to select for virus
with altered surface receptor
Rabies
Reo
o Use mutagen and grow virus at 32 degrees.
Selects for temperature-sensitive virus. Grows in
upper respiratory tract but not lower
Flu (new vaccine)
Respiratory syncytial virus
Passage
progressively
at
cold
temperatures
Can be re-assorted to so that coat is the
strain that is this years flu strain
o Deletion mutants
Suppression unlikely (but caution in HIV)
Viable but growth restrictions
Problems: Oncogenicity in some cases
(adeno, retro)
o Recombinant DNA
Single gene (subunit)
Problems
Surface glycoprotein poorly
soluble - deletion?
Poorly immunogenic
Post-translational modifications
o Chemically synthesized peptide
Malaria
Poorly immunogenic
Vaccines
o 1796 Jenner: wild type animal-adapted virus
o 1800s Pasteur: Attenuated virus
o 1996 DNA vaccines
The third vaccine revolution
DNA vaccines
o DNA vaccines are at present experimental, but
hold promise for future therapy since they evoke
both humoral and cell-mediated immunity,
without the dangers associated with live virus
vaccines
o Plasmids are easily manufactured in large
amounts
o DNA is very stable
o DNA resists temperature extremes so storage
and transport are straight forward
o DNA sequence can be changed easily in the
laboratory. This means that we can respond to
changes in the infectious agent
o By using the plasmid in the vaccinee to code for
antigen synthesis, the antigenic protein(s) that
are produced are processed (post-translationally
modified) in the same way as the proteins of the
virus against which protection is to be produced.
This makes a far better antigen than purifying
that protein and using it as an immunogen.
o Possible Problems
Potential integration of plasmid into
host genome leading to insertional
mutagenesis

Induction of autoimmune responses


(e.g. pathogenic anti-DNA antibodies)
Induction of immunologic tolerance (e.g.
where the expression of the antigen in
the host may lead to specific nonresponsiveness to that antigen)
Examples of vaccine developments
o Smallpox
Variolation
1% v. 25% mortality
Life-long immunity
No drift or shift
Jenner 1796 : Cowpox/Swinepox
1800s
Compulsory
childhood
vaccination
1930s Last natural UK case
1940s last natural US case
1958 WHO program
October 1977: Last case (Somalia)
No animal reservoir
Lifelong immunity
Subclinical cases rare
Infectivity does mot precede overt
symptoms
One Variola serotype
Effective vaccine
Major commitment by governments
Polio
o Killed virus vaccine (Salk, 1954)
o Live attenuated oral polio vaccine( Sabin, 1957)
o The inactivated Salk vaccine is recommended for
children who are immunosuppressed.
Measles
o Live attenuated virus grown in chick embryo
fibroblasts, first introduced in the 1960s.
o Etiology: Measles virus
o Incubation: 8 to 12 days
o Clinical
Manifestations:
cough,
coryza,
conjunctivitis, erythematous maculopapular rash,
fever, Koplik Spots, complications include
Encephalitis, Pneumonia, and SSPE
Mumps
o Live attenuated virus developed in the 1960s
o MMR vaccine
o Etiology: Mumps Virus
o Incubation: 16 to 18 days
o Clinical Manifestations:
Swelling of the salivary glands
Complications
include
Meningitis,
Orchitis, Encephalitis, and Deafness
Rubella
o Live attenuated virus
o Etiology: Rubella Virus
o Incubation: 14 to 21 days
o Clinical Manifestations: Congenital, cataracts,
deafness, mental retardation, Postnatal mild
disease, erythematous maculopapular rash,
postauricular lymphadenopathy

Hepatitis B
o

o
o
o
o

Two vaccines are in current use:


A serum derived vaccine
A recombinant vaccine
Etiology: Hepatitis B Virus
Incubation: 120 days (average)
Clinical Manifestations: jaundice; anorexia,
nausea and vomiting; malaise
Complications include the development of a
chronic carrier state with a high risk for
Hepatocellular Carcinoma (liver cancer)

Hepatitis A
o Formalin-inactivated , cell cultured-derived virus,
Influenza
o New vaccines are produced every year
Modes of immunization
o Passive immunization - administration of
antibody-containing
serum
to
provide
immediate, but temporary protection. Doesn't
activate a lasting specific immune response.
o Natural immunization - Provides immunity for
diphtheria, tetanus, streptococcus, rubella (red
measles), rubella (German measles), mumps,
polio, and others.
o Artificial immunization - often used as antitoxins
for things such as black widow spider and snake
bites, botulism, and tetanus. Important for some
infectious diseases such as rabies, since it
provides immediate protection rather than
waiting the 7-10 days for a protective response
to develop from active immunization.

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