Transcript NEW TECHNOLOGIES IN VACCINES

NEW
TECHNOLOGIES IN
VACCINES
• 1918-19 Flu Pandemic
• >500,000 people died in the US
• In 2009 a new strain of influenza emerged that had some
characteristics similar to the 1918 flu strain
• Pandemic – when an infectious disease breaks out worldwide –
smallpox, bubonic plague, HIV, flu
• Circulates among animals as well as humans
• Key weapon against influenza pandemics – Vaccinations
• Main goal of vaccinations is preventing disease
• State of NC requires vaccines against 10 different diseases
Responding to
Pandemics
• Vaccinations not only protect the vaccinated person, but also
protects the community as a whole
• Protects those too young to be vaccinated, those allergic to
vaccine ingredients and those with weakened immune systems
• Researchers working on vaccines against HIV, malarie and
chlamydia
• Immune system – protects from diseases caused by pathogenic
organisms
• Includes viruses, bacteria, protozoa and worms
• Mechanical barriers – skin, mucus – first line of defense
against microorganisms
• Purpose of vaccine is to jump-start immune response by
introducing the person to the disease-causing agent
• Vaccines contain enough of the disease agent to cause the
response without making the person sick
• Immune system can recognize protein molecules that belong to
the body and those that don’t
How Vaccinations Work
• Foreign proteins are called antigens
• White blood cells recognize surface proteins on disease agents
as antigens
• Macrophages – the PacMan of the immune system – engulfs
invaders
• T cells and B cells are activated to make antibodies – proteins
shaped to attach to the antigens
• Antibodies bind to the antigens which marks them for
destruction by the macrophages and T cells
• Once the immune system has learned to make antibodies
against a particular disease, it makes both T and B memory
cells that remain in the body for many years
• Vaccinations work by triggering this response
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Live but weakened disease agents (attenuated)
Inactivated or killed disease agents
Subunit vaccines
Toxoid vaccines – help the body to develop antibodies to
toxins released by bacteria
• Conjugate vaccines – help the immune system of infants and
young children recognize the polysaccharide coatings of some
bacteria that disguise them from immature immune systems
• DNA vaccines – experimental stages
• Recombinant vector vaccines – still experimental
Types of Vaccines
• Edward Jenner – credited with discovering the smallpox
vaccine
• Deliberately infected people with cowpox – mild disease
related to smallpox
• When the infected people recovered, he deliberately infected
them with smallpox and found them to be immune
• Today researchers weaken or attenuate pathogens by growing
them in a series of non-human cell cultures and select those
with lowered capability to reproduce in humans
• Now have live, attenuated vaccines for MMR, chickenpox and
influenza
• Live and attenuated vaccines effective in inducing full
protection
• Problems with this type of vaccine:
• Viruses are still “live” and can mutate to a more dangerous
form
• Those persons with weakened immune systems get sick
from even the weakened form
• Need constant refrigeration to remain effective which makes
distribution difficult
• Inactivated or killed disease agents are made by destroying the
disease agent’s DNA with chemicals, heat or radiation to
prevent reproduction
• This method keeps some of the disease organism’s proteins
intact
• These proteins are purified and packaged to make the vaccine
• Can be stored without refrigeration
• Weaker response means that more booster shots are required to
maintain immunity
• Smallpox vaccination eradicated smallpox
• Polio may be eradicated next
• Disease that routinely cause death greatly reduced in the
US
• Vaccination does have risk
• Risk of death or serious complications from measles
vaccination is <1 in 1,000,000
• 1 of 1,000 people who catch measles die
• Common myth is that vaccination leads to autism
• Two large studies show there is no connection between
the two
Vaccine Fears
• Controversies developed around Gardasil and Cervarix for
HPV
• HPV most common STD in the US
• Vaccination requires three doses and is relatively expensive
• Not known how long it protects
• Cervical cancer affects 11,000 women/year in US and kills
almost 4,000
• Prevents abnormal Pap smears that often lead to biopsy
• Social controversy surrounds HPV saying it may lead girls to
feel it is safer to have sex
• Vaccine does not prevent pregnancy or STDs
• FDA must approve vaccines for use
• In-vitro, animal testing clinical trials
• Researchers use cell and tissue cultures to assess cellular
response to new vaccines
• Ferrets used in flue vaccine research
• Mice and monkeys used for vaccines for other diseases
• Application has to be made to FDA to test on humans
Vaccine Development
Process
• Eggs
• Injecting fertilized chicken eggs with weakened strains of
influenza virus
• Replicates in the egg for several days
• Separated from the egg and exposed to chemicals to
inactivate the virus DNA
• Outer proteins of virus purified and tested to measure
yield, concentration and sterility of these proteins
• Packaged into vials
• Takes five to six months to produce when a new strain is
identified
• Contamination serious threat – has to be controlled
Manufacturing
Vaccines
• Cell culture
• Antigen is grown in large vats of cells
• Vats are called bioreactors and are completely closed from
contact with outside environment
• After vats are filled with cells, they are infected with the virus
• Virus replicates in the cells, producing lots of antigen and
killing the cells
• Antigen harvested, purified, tested, packaged and tested again
• Careful quality control and documentation at each step
• Significantly faster than egg process
• Pharming
• Plant-based vaccines
• Live vaccine not used – new strain of influenza isolated and
characterized, gene for its main surface protein is sequenced
• Sequence inserted into a plasmid (small piece of DNA) which
can replicate independently inside bacterial cells
• Plasmids transferred into Agrobacterium tumefaciens – soil
bacterium that normally causes plant disease
• Tobacco plants grown in controlled greenhouse are put in a
vacuum tank and air is sucked out of the spaces inside leaves
• Plasmid with the virus surface protein pulled into the leaf when
vacuum released
• After several days leaves are harvested and virus surface
protein extracted and purified
• Packaged for delivery as a vaccine
• Able to produce >10 million doses of flu vaccine in one month
• Safer, non-infectious and more stable for distribution
• Some disease organisms pose complex problems to
vaccine developers
• Need rapid and economical manufacturing techniques to
produce large amounts
• Vaccine products must be pure and stable – refrigeration a
problem
• Researchers working on introducing the vaccines into
food for consumption rather than shots
• Mutations of viruses cause problems with developing a
vaccine making it necessary to change the vaccine
constantly
Challenges in Vaccine
Research
• Protozoans much larger and present multiple possible surface
proteins that the immune system could attack
• Have a complex life cycle with different stages of parasite
growth within different cells and tissues
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Purchasing raw materials
Production
Packaging
Distribution
Researchers
Educators
Technicians
Support personnel
Careers in Vaccine
Manufacturing