NEW TECHNOLOGIES IN VACCINES

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

Careers in Vaccine Manufacturing

• Purchasing raw materials• Production• Packaging• Distribution• Researchers• Educators• Technicians• Support personnel