Lessons from studies with murine cytomegalovirus that could lead to a safe live attenuated vaccine for human cytomegalovirus

Access Microbiology
Clive Sweet

Abstract

Studies with a murine cytomegalovirus mutant tsm5 suggested two possible approaches to producing a live attenuated human cytomegalovirus vaccine. One approach would be to use a combination of five to six mutants where an attenuating mutation in the gene of one mutant is compensated by the wild-type version in a second mutant, which in turn has a mutation in a different gene compensated by the wild-type version in a third mutant, etc. Important genes in this approach could include those involved in DNA replication. The importance of the carboxy terminase of the primase gene (M70/UL70) for its function suggested a second approach where some of the natural codons in this region could be substituted with synonymous non-preferred (minor) codons that would reduce the replication fitness of the mutant.

References

Oct 1, 1995·The Journal of Pediatrics·P R Krause, D M Klinman
Jul 28, 1999·FEMS Microbiology Reviews·C Sweet
Jul 13, 2004·Trends in Biotechnology·Claes GustafssonJeremy Minshull
Aug 13, 2004·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Ann M ArvinUNKNOWN National Vaccine Advisory Committee
Jun 3, 2005·The New England Journal of Medicine·M N OxmanUNKNOWN Shingles Prevention Study Group
Nov 23, 2010·Expert Review of Vaccines·Heungsup Sung, Mark R Schleiss
Oct 17, 2013·Vaccine·Philip R KrauseStanley A Plotkin
Nov 9, 2018·Frontiers in Microbiology·Gaetan LigatSébastien Hantz

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