2. WHAT ARE VIRUSES
• Viruses are intracellular parasites unable to survive without
a living host
• Non-living ?; do not follow Koch’s Postulates
• They cannot reproduce or metabolize on their own because
they lack the self-machinery to do so Obligatory replicate
inside host cells using host metabolism
• A single infectious virus particle is termed a Virion that acts
as the vehicle for transmission
• All viruses consist of either double- or single-
stranded DNA or RNA that is linear or circular (or
fragmented)
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3. VIRUSES
• A virus is a submicroscopic obligate parasitic particle that infects
cells in biological organisms.
• Viruses are non-living particles that can only replicate when an organism reproduces the
virulent RNA or DNA.
• Among other things, viruses do not move, metabolize, or decay on their own. Viruses
are obligate intracellular parasites that lack the cellular machinery for self-reproduction.
• Viruses infect eukaryotes and prokaryotes such as bacteria; bacteriophages.
• Typically viruses carry a small amount of genetic material, either in the form of
RNA or DNA, but not both, surrounded by some form of protective coat consisting
of proteins, lipids, glycoproteins or a combination.
• The viral genome codes for the proteins that constitute this protective coat, as
well as for those proteins required for viral reproduction that are not provided by
the host cell.
3
4. HISTORICAL BEGINNING
Smallpox was the first disease people tried to prevent by
purposely inoculating themselves with other types of infections.
Inoculation is believed to have started in India or China before
200 BC. Physicians in China immunized patients by picking off
pieces from drying pustules of a person suffering from a mild
case of smallpox, grinding the scales to a powdery
substance, and then inserting the powder into the person's nose
in order for them to be immunized. In 1718, Lady Mary Wortley
Montague reported that the Turks have a habit of deliberately
inoculating themselves with fluid taken from mild cases of
smallpox. Lady Montague inoculated her own children in this
manner 4
5. ORIGIN OF VACCINES
In 1796, during the heyday of the smallpox virus in Europe, an English
country doctor, Edward Jenner, observed that milkmaids would sometimes
become infected with cowpox through their interactions with dairy cows'
udders. Cowpox is a mild relative of the deadly smallpox virus. Building on
the foundational practice of inoculation, Jenner took infectious fluid from the
hand of milkmaid Sarah Nelmes. He inserted this fluid, by scratching or
injection, into the arm of a healthy local eight year old boy, James Phipps.
Phipps then showed symptoms of cowpox infection. Forty-eight days
later, after Phipps had fully recovered from cowpox, Jenner injected some
smallpox-infected matter into Phipps, but Phipps did not later show signs of
smallpox infection
5
7. VACCINES [BACKGROUND]
• Vaccine comes from the Latin word ―vacca‖ which pertains to
―cows‖
• Based on the practice of variolation which was inoculating
healthy individuals with weak forms of smallpox
• 1st Vaccine (1796): Edward Jenner inoculated milkmaids with
cowpox to confer protective immunity against smallpox.
• 1st Attenuated Vaccine (1885): Louis Pasteur developed a
vaccine to protect against rabies; vaccine is made from viable
virus with reduced virulence (lower degree of pathogenicity).
7
8. VACCINES [BACKGROUND]
• Most damage to a cell is done too early before any clinical
symptoms of disease appear. Treatment becomes
difficult, therefore, prevention is preferred over post-exposure
vaccines.
• The Main Idea: Vaccines contain a weak form of a virus/microbe
that is not pathogenic
• Vaccines are used to protect a large number of people – fight
against epidemics and pandemics.
• Good vaccines elicit a secondary immune response that will
eliminate the pathogen.
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9. TIMELINE OF VACCINES
• 18th century
• 1796 First vaccine for smallpox, first vaccine for any disease
• 19th century
• 1882 First vaccine for rabies
• 20th century
• 1932 First vaccine for yellow fever
• 1945First vaccine for influenza
• 1952 First vaccine for polio
• 1954 First vaccine for Japanese encephalitis
• 1957 First vaccine for adenovirus-4 and 7
9
10. TIMELINE OF VACCINES
• 1962 First oral polio vaccine
• 1964 First vaccine for measles
• 1967 First vaccine for mumps
• 1970 First vaccine for rubella
• 1974 First vaccine for chicken pox
• 1977 First vaccine for pneumonia
• 1978 First vaccine for meningitis
• 1981 First vaccine for hepatitis B
• 1992 First vaccine for hepatitis A
• 1998 First vaccine for rotavirus 10
11. VACCINES BASICS
• The principle of vaccination is to induce a "primed" state in the vaccinated subject so that, following
exposure to a pathogen, a rapid secondary immune response is generated leading to the accelerated
elimination of the organism and protection from clinical disease. Success depends on the generation of
memory T and B cells and the presence in the serum of neutralizing antibody.
• Attributes of a good vaccine
• 1.Ability to elicit the appropriate immune response for the particular pathogen:
• Tuberculosis - cell mediated response
• most bacterial and viral infections - antibody
• 2. Long term protection
ideally life-long
3. Safety
vaccine itself should not cause disease
4. Stable
retain immunogenicity, despite adverse storage conditions prior to administration
5. Inexpensive
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12. VACCINES IMITATE AN
INFECTION
• Vaccines contain a weakened form of the
microbe that doesn’t cause disease or
reproduce
• Vaccines stimulate the macrophages, which
present the antigens to T and B cells
• The mock infection is rapidly cleared, and you
are left with a supply of memory T cells and B
cells to protect you against of future infection
of this type 12
15. THE IMMUNE SYSTEM & RESPONSE AND VACCINES
• Once vaccinated, the immune system takes a week and
upwards to begin fighting off the organism.
• Immunity is conferred once the immune system is ―trained‖
to resist a certain disease a vaccine is developed for
• Artificially Acquired Immunity is provided
• Childhood vaccinations are highly encouraged against:
• Measles, Mumps, Rubella, Polio, Hepatitis A &
B, Diphtheria, Pertussis, Tetanus, Chicken
Pox, HIB, Rotavirus, Meningococcal disease, and Influenza.
15
16. THE IMMUNE SYSTEM & RESPONSE
• Macrophages: white blood cells that detect and engulf viral
antigens; microbes are carried to lymphocytes
• Within lymph nodes, T and B cells are activated
• T cells: able to recognize virus infected cells early in infection
period and release cytotoxins to destroy them
• B cells: secrete antibodies that bind antigens on the virus
surface. This coats the virus and prevents infection. B-cells can
also recognize virus infected cells late in infection Ideally, good
vaccines evoke both T and B cells
• Antibodies will activate macrophages to ―engulf ‖ viral antigens
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18. LIVE (ATTENUATED) VACCINES
• Consist of a live form of the virus that has been
artificially weakened; select for mutants that will cause
wild-type infection without onset of disease
• Usually only takes 1 or 2 doses to confer life long
immunity (childhood vaccines).
• Must be careful of the small chance of reversion to a
more virulent form
• Elicit good immune response, inexpensive, but must be
cautiously stored to maintain viability
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19. INACTIVATED VACCINES
• Using heat, radiation or chemicals a virus is killed and is no longer infectious
• WHY USE AN INACTIVATED VIRUS?
• Attenuated strains have yet to be developed
• Reversion to virulent forms is a high occurrence
• Requires no refrigeration
• The downside is that the immunogenicity is lowered and multiple doses will
be required (i.e. booster shots)
• Adjuvants: administered simultaneously to enhance immune response
• Combination vaccines: DTP and MMR
• More expensive to prepare
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20. VACCINES IN GENERAL USE
Measles
• Live attenuated virus grown in chick embryo
fibroblasts, first introduced in the 1960's. Its
extensive use has led to the virtual eradication of
measles in the first world. In developed
countries, the vaccine is administered to all children
in the second year of life (at about 15 months).
However, in developing countries, where measles is
still widespread, children tend to become infected
early (in the first year), which frequently results in
severe disease. It is therefore important to
administer the vaccine as early as possible (between
six months and a year). If the vaccine is
administered too early, however, there is a poor take
rate due to the interference by maternal antibody.
For this reason, when vaccine is administered before
the age of one year, a booster dose is recommended
a months. 20
21. VACCINES IN GENERAL USE
Mumps
• Live attenuated virus developed in the
1960's. In first world countries it is
administered together with measles and rubella
at 15 months in the MMR vaccine.
• The current "Jeryl Lynn" strain of the mumps
vaccine was developed by Dr. Maurice Hillman
from the mumps virus that infected his 5-year-
old daughter (whose name was Jeryl Lynn).
This vaccine, combined with rubella or both
rubella and measles vaccines (MMR), has
been widely used worldwide (300 million doses
21
given) since it was approved
22. VACCINES IN GENERAL USE
Polio
• Two highly effective vaccines containing all 3 strains of poliovirus are in
general use:
• The killed virus vaccine (Salk, 1954) is used mainly in
Sweden, Finland, Holland and Iceland.
• The live attenuated oral polio vaccine (Sabin, 1957) has been
adopted in most parts of the world; its chief advantages being: low
cost, the fact that it induces mucosal immunity and the possibility
that, in poorly immunized communities, vaccine strains might replace
circulating wild strains and improve herd immunity. Against this is the
risk of reversion to virulence (especially of types 2 and 3) and the fact
that the vaccine is sensitive to storage under adverse conditions. -
Orimune®
• The inactivated Salk vaccine is recommended for children who are
immunosuppressed.
• 3 types of live polio virus, magnesium chloride, amino acid, polysorbate
80, purified water, neomycin, sulphate, streptomycin, penicillin and
monkey kidney cell cultures.
22
23. VACCINES IN GENERAL USE
Rubella
• Live attenuated virus. Rubella causes a mild febrile illness in children, but
if infection occurs during pregnancy, the fetus may develop severe
congenital abnormalities. Two vaccination policies have been adopted in
the first world. In the USA, the vaccine is administered to all children in
their second year of life (in an attempt to eradicate infection), while in
Britain, until recently, only post pubertal girls were vaccinated. It was
feared that if the prevalence of rubella in the community fell, then
infection in the unimmunized might occur later - thus increasing the
likelihood of infection occurring in the child-bearing years. This
programme has since been abandoned in Britain and immunization of all
children is the current practice.
• MMR — live measles virus, live mumps virus, live rubella
virus, chick embryo, human foetal cells, neomycin, sorbitol, gelatine.
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24. VACCINES IN GENERAL USE
Rabies
• No safe attenuated strain of rabies virus has yet been developed for
humans. Vaccines in current use include:
• The neurotissue vaccine - here the virus is grown in the spinal cords of
rabbits, and then inactivated with beta-propiolactone. There is a high
incidence of neurological complications following administration of this
vaccine due to a hypersensitivity reaction to the myelin in the preparation
and largely it has been replaced by
• A human diploid cell culture-derived vaccine (also inactivated) which is
much safer.
There are two situations where vaccine is given:
a) Post-exposure prophylaxis, following the bite of a rabid animal:
A course of 5-6 intramuscular injections, starting on the day of
exposure. Hyperimmune rabies globulin may also administered on
the day of exposure.
• b) Pre-exposure prophylaxis is used for protection of those
whose occupation puts them at risk of infection with rabies; for
example, vets, abbatoir and laboratory workers.
This schedule is 2 doses one month apart ,and a booster dose one
year later. (Further boosters every 2-3 years should be given if
risk of exposure continues).
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25. VACCINES IN GENERAL USE
Influenza
• Repeated infections with influenza virus are common due to rapid
antigenic variation of the viral envelope glycoproteins. Antibodies
to the viral neuraminidase and haemagglutinin proteins protect the
host from infection. However, because of the rapid antigenic
variation, new vaccines, containing antigens derived from
influenza strains currently circulating in the community, are
produced every year.
Surveillance of influenza strains now allows the inclusion of
appropriate antigens for each season.The vaccines consist of
partially purified envelope proteins of inactivated current influenza
A and B strains.
• Individuals who are at risk of developing severe, life
threatening disease if infected with influenza should receive
vaccine. People at risk include the elderly,
immunocompromised individuals, and patients with cardiac
disease. In these patients, protection from disease is only
partial, but the severity of infection is reduced. 25
26. VACCINE IN SPECIAL CIRCUMSTANCES
• Varicella-Zoster virus
• A live attenuated strain of varicella zoster virus has
been developed. It is not licensed in South Africa
for general use, but is used in some oncology units
to protect immuno-compromised children who have
not been exposed to wild-type varicella zoster virus.
Such patients may develop severe, life threatening
infections if infected with the wild type virus.
26
27. VACCINES IN SPECIAL CIRCUMSTANCES
Yellow Fever
• The 17D strain is a live attenuated vaccine
developed in 1937. It is a highly effective
vaccine which is administered to residents in
the tropics and travelers to endemic areas. A
single dose induces protective immunity to
travelers and booster doses, every 10
years, are recommended for residents in
endemic areas.
27
28. HEPATITIS B VACCINATION EMERGING
NEED IN VACCINATION
• Hepatitis B
• Two vaccines are in current use: a serum derived vaccine and a
recombinant vaccine. Both contain purified preparations of the
hepatitis B surface protein.
• The serum derived vaccine is prepared from hepatitis B surface
protein, purified from the serum of hepatitis B carriers. This
protein is synthesised in vast excess by infected hepatocytes
and secreted into the blood of infected individuals. A vaccine
trial performed on homosexual men in the USA has shown
that, following three intra-muscular doses at 0, 1 and 6
months, the vaccine is at least 95% protective.
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29. NEWER VACCINES FOR HEPATITIS B
INFECTIONS
• A second vaccine, produced by recombinant DNA
technology, has since become available. Previously, vaccine administration
was restricted to individuals who were at high risk of exposure to hepatitis B,
namely: infants of hepatitis B carrier mothers, health care workers,
homosexual men and intravenous drug abusers. However, hepatitis B has
been targetted for eradication , and since 1995 the vaccine has been
included in the universal childhood immunization schedule. Three doses are
given; at 6, 10, and 14 weeks of age. As with any killed viral vaccines, a
booster will be required at some interval (not yet determined, but about 5
years) to provide protection in later life from hepatitis B infection as a
venereal disease.
• HEPATITIS B — Hepatitis B virus gene, aluminium hydroxide, mercury,
formaldehyde. For the genetically engineered vaccine: aluminium
hydrochloride, sodium chloride and mercury
29
30. ROTATEQ AND ROTAVIRUS INFECTIONS
30
• Rotateq is a live, oral Pentavalent vaccine that contains five
rotaviruses produced by reassortment. The rotavirus A parent
strains of the reassortants were isolated from human and bovine
hosts. Four reassortant rotaviruses express one of the outer
capsid, VP7, proteins (serotypes G1, G2, G3, or G4) from the
human rotavirus parent strain and the attachment protein VP4
(type P7) from the bovine rotavirus parent strain. The fifth
reassortant virus expresses the attachment protein VP4, (type
P1A), from the human rotavirus parent strain and the outer
capsid protein VP7 (serotype G6) from the bovine rotavirus
parent strain. In February 2006 approved RotaTeq for use in the
United States.
31. WHO RECOMMENDS THE ROTAVIRUS
VACCINE
31
• WHO recommends that rotavirus vaccine for
infants should be included in all national
immunization programmes. In countries where
diarrhoeal deaths account for ≥10% of mortality
among children aged <5 years, the introduction
of the vaccine is strongly recommended. WHO
recommends that the first dose of either RotaTeq
or Rotarix be administered at age 6–15 weeks.
The maximum age for administering the last
dose of either vaccine should be 32 weeks.
32. HPV – HUMAN PAPILLOMAVIRUS
• Genital HPV most common sexually transmitted
infection in US
• Cause of cervical cancer, genital warts, anal & penile
cancer
• By the age of 50, 80% of women will have contracted at
least 1 strain of the virus
• Fortunately, many strains can be cleared by immune
system before symptoms occur
• HPV vaccine is a preventative measure against initial
infection 32
33. HPV – HUMAN PAPILLOMAVIRUS
• HPV – Human Papillomavirus
• Types 16 and 18 cause 70% of the cases of cervical
cancer and types 6 and 11 cause 90% of genital
warts
• HPV Vaccine, Gardasil, protects against these
strains
• Pap smears are still recommended since there are
over 100 HPV strains identified, many of which can
also cause cancer
33
34. SUBUNIT VACCINES
• Immune response can be stimulated by one or a set of viral
proteins.
• This was first demonstrated by hepatitis B and influenza
vaccines
• These can be a lot safer than attenuated or inactivated vaccines
• The subunits included are determined by identifying which
proteins the antibodies recognize.
• Subunits vaccines
• Composed solely of purified protein can be delivered to body by
means of a non-pathogenic virus, bacteria, etc
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35. DNA VACCINES
• DNA vaccines are at present experimental, but hold promise for future therapy since they will
evoke both Humoral and cell-mediated immunity, without the dangers associated with live virus
vaccines.
• The gene for an antigenic determinant of a pathogenic organism is inserted into a
plasmid. This genetically engineered plasmid comprises the DNA vaccine which is then
injected into the host. Within the host cells, the foreign gene can be expressed (transcribed
and translated) from the plasmid DNA, and if sufficient amounts of the foreign protein are
produced, they will elicit an immune response. in recent years a new type of vaccine, created
from an infectious agent's DNA called DNA vaccination, has been developed. It works by
insertion (and expression, triggering immune system recognition) into human or animal
cells, of viral or bacterial DNA. These cells then develop immunity against an infectious
agent, without the effects other parts of a weakened agent's DNA might have. As of 2006, DNA
vaccination is still experimental, but shows some promising results.
35
36. RECOMBINANT VACCINES
36
• Recombinant vaccines are those in which genes for desired antigens are
inserted into a vector, usually a virus, that has a very low virulence.
• The vector expressing the antigen may be used as the vaccine, or the
antigen may be purified and injected as a subunit vaccine.
• The only recombinant vaccines currently in use in humans is the Hepatitis B
Virus (HBV) vaccine, and HPV which is a recombinant subunit vaccine
• Hepatitis B surface antigen is produced from a gene transfected into yeast
cells and purified for injection as a subunit vaccine.
• This is much safer than using attenuated HBV, which could cause lethal
hepatitis or liver cancer if it reverted to its virulent phenotype.
• Recombinant DNA techniques can also be used to make safer attenuated
pathogen vaccines….
37. VACCINES – A METHOD OF PREVENTION
• Influenza
• Nearly 40,000 deaths and 115,000 hospitalized yearly in US
• Educated guess on most probable form of virus
• Also comes in nasal spray of attenuated form
• New vaccines must always be produced due to high antigenic
variation
• At risk individuals (elderly, Immunodeficient) should be
vaccinated
37
38. HUMAN IMMUNODEFICIENCY VIRAL
VACCINES
• Currently in use: subunit, recombinant, and DNA vaccines
• Method:
• Inhibit fusion to host cell
• Inhibit reverse transcriptase
• Stops any viral integration into host cells
• Targets functional HIV viral proteins
• Viral exit form host cell is stopped
• HIV continuously mutates and recombines to escape effects of
vaccine
• It can also be transmitted as a free virus
38
39. WHY HIV IS A HARD TARGET
39
• Spread both sexually and blood so need both mucosal immune responses
and systemic
• Probably transmitted both as cell-free virus and cell associated and therefore
probably need both neutralizing antibody AND T-cell mediated immune
response
• Worst of all, our own immune systems can’t stop the replication of the virus
• Here, the virus’s evolution is the central issue
• maybe it will never be possible to generate immune protection against the
virus
• Ignoring this, for the moment, you then still would need to contend with the
tremendous genetic diversity of the virus
40. VACCINES – A SOURCE OF CONTROVERSY
• Some health critics say vaccination benefits are exaggerated. Claim that
vaccines are not solely responsible for reducing mortality rates of any one
disease.
• Opponents find that even vaccinated individuals still contract disease
• Adverse effects (although RARE) can be worse than the naturally occurring
disease
• Vaccine schedules are not designed for multiple exposure to immunogens at
young ages
• Some diseases and conditions (leukaemia, MS, SIDS) have increased with
the use of vaccinations
• Some vaccines contain mercury, formaldehyde, neomycin, and other toxic
chemical components
40
42. • Vaccines still most
effective preventative
measure you can take to
protect yourself from
disease
• Remains one of the most
affordable methods
• Not only are you
protecting yourself, you
are protecting everyone
around you.
DO NOT NEGLECT VACCINATION
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