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New Approaches to Attenuated Hepatitis a Vaccine Development: Cloning and Sequencing of Cell-Culture Adapted Viral cDNA.

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Annual rept. 15 Sep 86-14 Sep 87,

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Hepatitis A virus HAV is a human picornavirus with a worldwide distribution. It poses a considerable threat to military forces of the United States due to its capacity for epidemic spread, and the fact that acute hepatitis A associated with primary infection with HAV is a protracted illness with a prolonged convalescence. No vaccine is currently available for prevention of infection with this medically important virus. Three general approaches to HAV vaccines have been considered, including development of an inactivated, cell-culture derived vaccine, an attenuated vaccine derived by extensive passage of virus in vitro, and more novel vaccines based on synthetic peptide or recombinant DNA technology. A detailed discussion of these approaches, all of which are beset with difficulties may be found in Report 1 of this contract, or in the review by Lemon. This contract has focused on understanding the molecular basis of attenuation of HAV, as such an understanding might open new approaches to development of an economic and effective HAV vaccine. The molecular mechanisms underlying either adaptation of HAV to growth in cell culture results in profound changes in the biologic characteristic of the virus and with continued passage of virus has been associated with a reduction in virulence in several different species of primates. A primary effort under support of this contract has therefore been the cloning and sequencing of the genome of a cell culture-adapted variant of HM175 strain HAV, and the identification of mutations in this virus that were associated with adaptation of this virus to growth in vitro.

Subject Categories:

  • Pharmacology
  • Microbiology

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