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Anti-Viral Vaccines
Sarah Pham
Medicinal Chemistry
March 27, 2008
Virus Basics
• 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
• Obligately 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 singlestranded DNA or RNA that is linear or circular (or
fragmented)
Virus Basics
• Nucleic Acid: Viral DNA or RNA enclosed within
the capsid that will be replicated within the host
cell
• Capsid: Made of proteins surrounding the nucleic
acid of a virus. It is made of capsomer subunits that
serve as a protective shield. It is also responsible for
attachment and penetration of host cell.
• Envelope: Some viruses’ capsids are enclosed by a
protective envelope consisting of glycoproteins
that comes from the host cell. It is used for cell
recognition and attachment
Virus Basics
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).
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.
The Immune System & Response
• 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,
Diptheria, Pertussis, Tentanus, Chicken Pox, HIB,
Rotavirus, Meningococcal disease, and Influenza.
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 “eat” viral
antigens
The Immune System & Response
• Elimination of the disease will leave many T and B
cells to convert into memory cells
• Recovering from the infection leaves you with a
supply of memory cells that will protect against
future infection
Vaccine Types
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
Vaccine Types
INACTIVATED VACCINES
-
Using heat, radiation or chemicals a virus is killed
and is no longer infectious
WHY USE AN INACTIVATED VIRUS?
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-
The downside is that the immunogenicity is lowered
and multiple doses will be required (i.e. booster
shots)
-
-
Attenuated strains have yet to be developed
Reversion to virulent forms is a high occurrence
Requires no refrigeration
Adjuvants: administered simultaneously to enhance
immune response
Combination vaccines: DTP and MMR
More expensive to prepare
Vaccine Types
SUBUNIT VACCINES
-
Vaccines only contain the antigens of a virus to
stimulate an immune response
Usually safer than attenuated or inactivated vaccines
-
-
-
Chances of reversion are low
Subunits are recognized by antibodies
Finding the correct subunit or specific
antigen/protein that antibodies will recognize is a
much more complex process
Yields low success rates and effects, but has great
potential
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
Vaccines – a method of
prevention
• HIV
• 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
Vaccines – a method of prevention
• 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
Vaccines – a method of prevention
• 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
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 (leukemia, MS,
SIDS) have increased with the use of
vaccinations
– Some vaccines contain mercury, formaldehyde,
neomycin, and other toxic chemical components
Vaccines
• BE SMART!
• 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.
References
1. Vaccineinformation.org – Vaccine information for the public and health professionals
2. Wolfe R, Sharp L (2002). "Anti-vaccinationists past and present". BMJ 325 (7361): 430–2.
3. Bonhoeffer J, Heininger U (2007). "Adverse events following immunization: perception and evidence". Curr Opin
Infect Dis 20 (3): 237–46.
4. Advanced Drug Delivery Reviews, 2004 (Vol. 56) (No. 10) 1367-1382 Morein, B., Hu KeFei, Abusugra, I
5. Immunization. MedlinePlus. U.S. National Library of Medicine (2007-12-27).
6. Plotkin, Stanley A. (2006). Mass Vaccination: Global Aspects - Progress and Obstacles (Current Topics in
Microbiology & Immunology). Springer-Verlag Berlin and Heidelberg GmbH & Co. K.
7. Lombard M, Pastoret PP, Moulin AM (2007). "A brief history of vaccines and vaccination". Rev. - Off. Int. Epizoot.
26 (1): 29–48.
8. Melinda Wharton. National Vaccine Advisory committee U.S.A. national vaccine plan
9. Cdc.org – Center for Disease Control website
10. Strathern, Paul (2005). A Brief History of Medicine. London: Robinson, p. 179.
11. Flint, S.J. Principles of Virology. 2nd edition. 2004. ASM Press: Washington D.C.