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1. Vaccines Currently Licensed in the U.S.
2. Vaccines Currently Licensed in the U.S. (Continued)
3. Vaccines Which Need Improvement
4. Vaccines Which Need Improvement (Continued)
5. Vaccine Candidates for Development in U.S.
6. Vaccine Candidates for Development in U.S. (Continued)
7. IVI Vaccine Development for Use in Developing Countries*
8. IVI Vaccine Development for Use in Developing Countries* (Continued)
9. IVI Vaccine Development for Use in Developing Countries* (Continued)
10. Annually Required Vaccine Doses in Taiwan*
11. Epidemic Infection Primarily Affect the Elderly The reasons are :
Decline in activity of immune system;
Susceptibility to infections such as TB, influenza and pneumonia;
Increasing emergence of antibiotic-resistance pathogens;
Elderly will be subjected to stressful situations.
12. Infectious Diseases of the Elderly 1. Mortality due to infectious diseases in the U.S.
Year Mortality per 100,000 persons
? 65 yrs Whole population
1980 271 41
1992 338 65
2. Infectious diseases in the elderly
Influenza
Bacterial pneumonia
Tetanus
Tuberculosis
Group B streptococcus
14. Prevention of Influenza and Vaccine Supply???????????????? 1. Influenza pandemic during 20 century.
1968 Hong Kong flu
1957 Asian flu
1918 Spanish flu – 20 million death worldwide, more than $ 1
billion in health care.
2. Vaccine preparation and Supply.
Jan--Manufacturers arrange eggs for growing virus.
Feb—Scientific committees recommend the strains to be used.
Mar—Settle precise vaccine formulation.
Apr—Manufacturers begin testing vaccines they have produced.
Jul-Aug—FDA approval for vaccine release. Vaccine
distribution to public.
Sep-Dec--Immunization
15. Research on Drug resistance to TB ????????????
16. Status of DNA Vaccine Early stage of DNA vaccination.
Plasmid DNA to protective antigens of influenza.
--Hemagglutinin (HA).
--Nucleoprotein (NP).
Induced both humoral and cell-mediated immunity.
DNA vaccines successfully tested in animal models.
Viruses– HIV, hepatitis B, bovine herpes virus, herpes simplex,
papilloma virus, hepatitis C.
Parasites– Malaria, leishmania.
Bacteria—TB, mycoplasma.
Immune responses
Humoral– IgM, IgG (IgG 2a), IgA.
Cell-mediated immune (CMI) response– CTL and T-cells.
Th1-like cytokine response– high levels of IL-2, INFg.
17. Protective Immunity in Mice with Influenza HA DNA
18. DNA Vaccine Against Tuberculosis Antigen 85– Ag85A, B, C.
Ag85 induced strong CMI—
Th1-like response, IL-2, INFg, and CTL
Heat-shock protein– hsp65
Hsp65 induced both humoral and CMI responses in mice.
Advantages over BCG vaccine
--Purified plasmid DNA induces less reactogenicity.
--BCG is a live organism that can cause disease in
immunocompromised people.
--BCG is reactive in a PPD skin test, causing interference
with TB screening.
--DNA vaccine will be cloned directly from the relevant
pathogenic mycobacterial strain.
19. Advantages of DNA Vaccines Non-infectious, non-replicating.
Proteins produced in native conformation.
Mimic the effects of live attenuated vaccines.
Physicochemical homogeneity; easy to incorporate several genes in a single vaccine.
Inexpensive and simplified production.
Stable and can be stored without the need of refrigerator.
Induction of CTLs and antibody response.
20. Clinical Trials of DNA Vaccines
21. Human Immune Deficiency Virus (HIV) Disease HIV disease
--WHO estimates that 5,000people become
infected daily.
--In the U.S., 400,000 people developed AIDS;
1 million people are infected with HIV-1;
40,000 adults are newly infected each year.
Obstacles for vaccine development
(a). HIV infects and destroys critical component of the
immune system.
(b). Lack of known correlates of immunity and an
ideal animal model.
(c). High degree of variation in HIV and its mode of
transmission.
22. Animal Models and HIV Variation Animal models– lack of an ideal model of HIV disease.
-- Chimpanzees infected with HIV do not develop disease.
-- Macaque monkeys develop simian IV causes AIDS-
like disease but differ from HIV.
HIV variation
(a). HIV-1 envelop gene is catagorized into 9 subtypes;
within each subtype there is substantial variation.
(b). High rate of replication an mutation.
-- First AIDS vaccine used LAI strain which was
different from most strains in infected people.
-- SF-2 and MN isolates
More representative strains isolated for N. Am. And
Europe.
24. Safety Concerns on DNA Vaccines Potential for insertion into the host genome, thereby increasing the risk of malignancy.
To trigger the development of autoimmune disease.
Induces immunologic tolerance.
Possibility of stimulating production of cytokines that change the host ability to respond to other vaccines.
25. Issues on Development of Edible Vaccines Selection of plant cells for gene expression
Banana, tomato.
Lettuce, carrots, potato, bean, and rice.
High Yield of protein antigen production
HBsAg
Norwalk virus capsid protein (NVCP)
Cholera and enterotoxigenic E. coli (LT-B)
Effective vaccine delivery
Adjuvants, e.g. LT-B
Immune stimulating factors, e.g. cytokines
Suppression of immunity to antigens in food.