Development of mutations useful for attenuating dengue viruses and chimeric dengue viruses
AssigneeThe United States of America, as represented by the Secretary, Dept. of Health and Human Services
InventorsStephen S. Whitehead, Brian R. Murphy, Kathryn A. Hanley, Joseph E. Blaney, Ching-Juh Lai
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Abstract
A menu of mutations was developed that is useful in fine-tuning the attenuation and growth characteristics of dengue virus vaccines.
Claims28
A flavivirus having a phenotype in which the viral genome is modified by the introduction of a mutation, singly or in combination, taken from the group consisting of the mutations of any of Table 1-37, preferably Table 37.
4-6. (canceled)
9-11. (canceled)
A method of identifying a mutation that restricts replication in human liver cells or a mutation that promotes growth in Vero cells comprising:
- (a) introducing mutations into a dengue virus genome to make mutant viruses;
- (b) screening the mutant viruses for a phenotype characterized by host-cell restriction in human liver cells or host-cell adaptation for improved replication in Vero cells;
- and
- (c) determining the genetic basis for the phenotype by direct sequence analysis of the virus genome.
(canceled)
A method of assembling a menu of mutations for use in fine-tuning the attenuation and growth characteristics of recombinant dengue viruses comprising (a) introducing mutations into a dengue virus genome to make mutant viruses;
- (b) screening the mutant viruses for a phenotype characterized by temperature sensitivity in Vero cells or human liver cells, host cell restriction in mosquito cells or human liver cells, host-cell adaptation for improved replication in Vero cells, or attenuation in mice;
- (c) determining the genetic basis for the phenotype by direct sequence analysis of the virus genome;
- and (d) performing multiple iterations of steps (a)-(c), whereby a menu of mutations is assembled.
Dependencies are inferred from the claim text.