Immunization against genital herpes with a vaccine virus that has defects in productive and latent infection

XJ Da Costa, CA Jones… - Proceedings of the …, 1999 - National Acad Sciences
XJ Da Costa, CA Jones, DM Knipe
Proceedings of the National Academy of Sciences, 1999National Acad Sciences
An effective vaccine for genital herpes has been difficult to achieve because of the limited
efficacy of subunit vaccines and the safety concerns about live viruses. As an alternative
approach, mutant herpes simplex virus strains that are replication-defective can induce
protective immunity. To increase the level of safety and to prove that replication was not
needed for immunization, we constructed a mutant herpes simplex virus 2 strain containing
two deletion mutations, each of which eliminated viral replication. The double-mutant virus …
An effective vaccine for genital herpes has been difficult to achieve because of the limited efficacy of subunit vaccines and the safety concerns about live viruses. As an alternative approach, mutant herpes simplex virus strains that are replication-defective can induce protective immunity. To increase the level of safety and to prove that replication was not needed for immunization, we constructed a mutant herpes simplex virus 2 strain containing two deletion mutations, each of which eliminated viral replication. The double-mutant virus induces protective immunity that can reduce acute viral shedding and latent infection in a mouse genital model, but importantly, the double-mutant virus shows a phenotypic defect in latent infection. This herpes vaccine strain, which is immunogenic but has defects in both productive and latent infection, provides a paradigm for the design of vaccines and vaccine vectors for other sexually transmitted diseases, such as AIDS.
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