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File: 970101_sep96_decls6_0004.txt
Subject: COVER SHEET FOR DOCUMENT TRANSMISSION
Unit: OTSG
Parent Organization: HSC
Box ID: BX003205
Folder Title: VACCINES TO PREVENT DIARRHEA IN OPERATION DESERT SHIELD
Document Number: 1
Folder Seq #: 14
1. PREVENNON OF SHIGELLA INFECTIONS. As many as 1000 cases of
shigallosis occur In our troops each week during Operation Desert Shield. The
problem may become worse as more new forces are deployed and the ooot weather
subsides. Over 90% of the @@ isolates isolated thus far are Shiaelia @; but
other serotypes, most commonly $. flexned, are endemic In the area and could
become a significant problem. Shicelia from this area are resistant to the commonly
used antibiotics. Currently c7iprofloxacin is the only oral antibiotic available for
treatment. Resistance to this drug has t>een documented In @ and could result
from widespread use of this antibiotic In the Area of Operations.
2. Our current vaccine EcSf2a-2 Is an E. cQU hybrid containing Shigetia Invasion
genes and Shiaella flexned 2a 0 antigen genes which has I>een further attenuated by
an amD mutation. This vaccine protected 70% of volunteers In the experimental
challenge model against the severe manifestations of shigeliosis which would debilitate
our troops. Twenty more Immunized volunteers will be challenged on I 1 December
1990 to confirm these results. EcSf2a-2 produced side effects such as fever,
malaise, or mild diarrhea in about 20% of volunteers after an initial dose of 2 X II?,
but none of these side effects were seen with 2 subsequent doses of 1.5 X I(?
organisms. In a previous trial where 1-1.2 X 109 organisms were given 3 times only
mild cramping In two volunteers after the third dose was seen. We believe that this Is
an effective vaccine that can t>e made safer by decreasing the Immunization dose.
Is to
modify our current EcSf2a-2 vaccine. the gene coding for the S. sonnet 0 side chain
has been cloned into a plasmid to express S. sonnet antigen in Ecsf2a-2. The levels
of expression are not as high as in the wild type organism and the plasmid Is not
suitable for human use because ft contains antibiotic markers. We propose to
construct a new plasmid suitable for use in a human vaccine which contains the genes
coding for the regulation and expression of the $. sonnei antigen. We believe that this
larger piece of DNA will express $. sonnei antigen at a level comparable to the wild
type S. sonnei strains. These molecular biology constructions should t>e completed by
January 1991. Manufacturing of the vaccine at the Salk Institute at Swiftwater, PA
should be complete and ready for IND submission by early February. Challenge
testing could begin in March. Large scale outpatient safety testing could begin In late
March with deployment to Desert Shield forces by mid-April. This process could be
accelerated by expedited review by the FDA.
Recommendation:
1) Rapid development of an E. cQU hybrid -5. sonnet vaccine which entails
scheduling of production facilities, expedited review of protocols, -scheduling of vaccine
testing centers, and Informing the FDA that this project has high priority.
4. Dr. John Robbins, National Instititues of Health, has developed conjugate vaccines
3
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Document 8 f:/Week-36/BX003205/VACCINES TO PREVENT DIARRHEA IN OPERATION DESERT SHIELD/cover sheet for document transmission:1224960931177
Control Fields 17
File Room = sep96_declassified
File Cabinet = Week-36
Box ID = BX003205
Unit = OTSG
Parent Organization = HSC
Folder Title = VACCINES TO PREVENT DIARRHEA IN OPERATION DESERT SHIELD
Folder Seq # = 14
Subject = COVER SHEET FOR DOCUMENT TRANSMISSION
Document Seq # = 1
Document Date =
Scan Date =
Queued for Declassification = 01-JAN-1980
Short Term Referral = 01-JAN-1980
Long Term Referral = 01-JAN-1980
Permanent Referral = 01-JAN-1980
Non-Health Related Document = 01-JAN-1980
Declassified = 24-DEC-1996