new technologies in vaccines. responding to pandemics 1918-19 flu pandemic >500,000 people died...
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Responding to Pandemics
• 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
• 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
How Vaccinations Work
• 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
• 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
Types of Vaccines
• 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
• 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
Vaccine Fears
• 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
• 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
Vaccine Development Process
• 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
Manufacturing Vaccines
• 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
• 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
Challenges in Vaccine Research
• 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
• 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