Strategies for developing new vaccines to combat emerging infectious diseases

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Strategies for developing new vaccines to combat
emerging infectious diseases Wen Yumei Ministry
of Education/Health, Key laboratory of Medical
Molecular Virology Shanghai Medical College,
Fudan University
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2S Close relationship between Science (infectious
diseases) and Society The financial input for
public health issues should be increased from the
government More emphasis on the rural area and
for peasants To switch the essence of health
problems a step forward, from treatment of
diseases to prevention, early diagnosis, and
blocking the progress to sequelae or
complications .
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Interactions between the established vaccines and
new forthcoming vaccines
Established Vaccines
New Vaccines
Gain experiences from established vaccines
Support appropriate projects Connect projects
with small scale production and pilot clinical
trial
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Vaccines in use, under clinical trial or in
preparation Inactivated or attenuated microbial
vaccines Recombinant protein vaccines Nucleic
acid vaccines Peptide-based vaccines Conjugated
vaccines Therapeutic vaccines Different delivery
routes are in use or under study
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Vaccines for stimulating innate immune responses
(when the pathogen is not identified) All-round
vaccines CpG, DNA Poly IC, Polysaccharides (
LPS) Non specific stimulants
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Changes of TLR9 mRNA expression after cpG
intradermal injection In mice
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Intradermal injection of CpG motif enhances
proinflammatory cytokine mRNA expression
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For All Round vaccines suggested areas
are Encouraged Experiments Prevention in
spread of diseases Effects in new borns and
aged animals Delivery in different routes
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Inactivated first aid microbial vaccines
against acute emerging diseases Develop vectors
or established vaccines that can be modified or
inserted with target genes. Develop inactivated
vaccine or vaccine-like biological product for
immediate prevention or blocking of the
pathogen. Preferably used topically
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Blocking with inactivated SARS Virus Inactivated
SARS virus (107copies/ml ) treated vero cells 1
hr. Control treated with medium. Challenged
with 107 copies/ml live virus. (1) TCID50
10-2.50 (blocked with inactivated virus)
TCID50 10-6.66 (blocked with medium) decreased
3.16 log(99.9) (2) TCID50 10-3.50
(blocked with inactivated virus) TCID50
10-6.66 (blocked with medium) decreased 2.16
log(99.0)
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Neutralizing antibodies in serum of mice
immunized intranasally
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Detection of IgA in tracheal lung wash of mice
immunized intranasally
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Serum anti-H3N2 in mice immunized intranasally
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Serum HAI titers
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Anti-H3N2 IgA titer in tracheal-lung wash fluid
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For First Aid vaccines Suggested support
areas Methods for inactivation for a broad range
of microbes Effective methods for delivery
Induction of mucosal immune responses
Adjuvants simple assays for measuring systemic
and local immune responses
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Antigen presentation modifying vaccines against
persistent emerging diseases Immune tolerance
against the persistent viral antigen
Antigen-antibody complex-specific plasmid DNA can
be processed and presented by both exogenous and
endogenous pathways
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Anti-HBs titer immunized with 6 injections of
YIC 90?g  
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Healthy adults HBV markers negative Three
injections at 4 week- intervals intramuscular
injections ( 30, 60, 90 micrograms of HBsAg per
injection). Another group 90 micrograms of HBsAg
per injection, for 6 injections. Liver function,
renal function, blood, heart, lung function
check up etc. all within normal range. Safe for
human used.
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Phase II B Clinical trial 240 patients in 12
hospitals Double blind 6 injections at 4 week-
intervals Follow for 6 months
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For modulation of antigen presentation, suggested
areas are The mechanisms of IC processing and
presentation Processing of IC-DNA Therapeutic
effects in viral persistent infections
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IN SUMMARY New vaccines against emerging
diseases are usually based on the established
vaccines. Aside from traditional
vaccines, Vaccines to stimulate non-specific
immune responses (all roundvaccines)
Inactivated vaccines to be used locally( first
aid vaccines) vaccines to regulate antigen
presentation ( for persistent infections) may be
considered.