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SUMMARY STATEMENT
Annual Report
Laboratory of Infectious Diseases
National Institute of Allergy and Infectious Diseases
October 1, 1982 to September 30, 1983
HEPATITIS
Hepatitis A Virus (HAV) . HAV Purchase Flonase is responsible for most epidemics of short
incubation hepatitis and thus represents a major target Price Of Flonase for vaccine development.
This virus was first visualized and identified by LID scientists and was
subsequently grown in tissue culture by workers at Merck, Sharp and Dohme.
Serial cultivation in primary African green monkey kidney (AGMK) tissue culture
rapidly leads to attenuation of HAV for chimpanzees as reported last year.
After 10 passages in AGMK cells, HAV was observed to be highly attenuated for
chimpanzees inoculated parenteral ly. Tenth passage HAV infected chimpanzees and
induced a strong immunological response but did not cause significant disease.
HAV Order Flonase passaged 20 times in AGMK was also attenuated for chimpanzees and retained
its antigenicity. However, twentieth passage HAV remains virulent for marmosets
( Saguinus mystax and Sanguinus labiatus ). Infected marmosets developed a rise
in serum alanine amino transferase (ALT). At this time it is not known whether
the response of chimpanzees or marmosets more accurately predicts the response
of susceptible individuals to tissue culture grown HAV. If the response of
chimpanzees more accurately reflects that of man, currently available AGMK
culture HAV should be satisfactorily attenuated for man. If the marmoset more
closely resembles man in response to HAV, it will be necessary to introduce
additional mutations into Buy Flonase the virus before it can be used safely for
immunization against human disease. This issue can only be resolved by
cautious, stepwise trials in volunteers which are now under consideration.
HAV has been cloned biologically by three successive terminal dilutions in
AGMK cells to yield a master seed that is being employed currently to prepare a
twentieth tissue culture passage suspension for use in clinical trials. In
addition, earlier (passage level 5) and later (passage level 26) virus stocks
are being cloned by terminal dilution to yield master seed for preparation of
HAV suspensions at the 10th and 30th passage level. These suspensions will be
evaluated in volunteers if the 20th passage suspension proves to be over- or
underattenuated. Preparation and safety-testing of HAV suspensions suitable for
study in volunteers represents a collaborative effort involving RIT
Laboratories, a subsidiary of Smith, Kline and French (Feinstone, Daemer,
Purcell ).
During the past year considerable progress was made in advancing our
understanding of the molecular aspects of HAV. Previously it had been
established that HAV was a picornavirus with most if not all of the
characteristics of an enterovirus. The virus is is a 27 nm particle with cubic
symmetry that contains four polypeptides and a single-stranded linear RNA
genome.
22-1
Because HAV is difficult to grow in tissue culture, a number of questions
remain Cost Of Flonase unanswered concerning its molecular biology. Because of the small amount
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