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1
|
|
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2
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- Responsible for 20-30% of the 2 million hospital acquired infections in
the U.S. each year and 20% of all endocarditis infections.
- Enterococcus faecalis and Enterococcus faecium account for 80-90% and
5-15% of enterococcal clinical
isolates respectively.
- Surge in strains resistant to antibiotics,
- including VRE (vancomycin resistant Enterococcus).
|
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3
|
- Generation of a panel of antibodies against specific surface antigens
for passive protection during hospitalization ”engineered polyclonal”
- Many surface antigens / virulence factors identified, few evaluated as
antibody targets
- Recombinant monoclonals can be evaluated for affinity, cross reactivity
and epitope specificity, providing valuable insight into potential of
antigen as immune target.
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4
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5
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6
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7
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8
|
- Antibodies found in patient sera are specific to target antigen.
- Gene disruption effects pathogenicity of Enterococcus (decrease in
colonization, biofilm disruption, adhesion inhibition).
- Identification of a homolog in E. faecium.
- Both anchored to peptidoglycan surface and
- can be expressed in culture.
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9
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10
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11
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12
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13
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14
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15
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16
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17
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18
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19
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20
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21
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22
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23
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24
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25
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26
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27
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28
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29
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30
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31
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32
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33
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34
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|
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35
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36
|
- Affinity mature lead candidates
- Evaluate antibody protection in mouse models. (single and combos)
- Continue to utilize antibodies as tools for improving our understanding
of regulation of surface antigen expression.
- Isolate antibodies to additional targets.
- Continue to improve screening and selection strategies.
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37
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- Ken Pinkston
- Dr. Peng Gao
|
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38
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39
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40
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Notes
