Live Attenuated Herpes Simplex Virus 2 Glycoprotein E Deletion Mutant as a Vaccine Candidate Defective in Neuronal Spread

• DOI: 10.1128/jvi.07203-11
• Publication Date: 2012-02-09T11:39:37Z
• Authors: Sita Awasthi; Elizabeth E. Zumbrun; Huaxin Si; Fushan Wang; Carolyn E. Shaw; Michael Cai; John M. Lubinski; Shana M. Barrett; John W. Balliet; Jessica A. Flynn; Danilo R. Casimiro; Janine T. Bryan; Harvey M. Friedman
• Keywords: Viral Shedding

A herpes simplex virus 2 (HSV-2) glycoprotein E deletion mutant (gE2-del virus) was evaluated as a replication-competent, attenuated live vaccine candidate. The gE2-del is defective in epithelial cell-to-axon spread and anterograde transport from the neuron cell body to axon terminus. In BALB/c SCID mice, caused no death or disease after vaginal, intravascular, intramuscular inoculation 5 orders of magnitude less virulent than wild-type when inoculated directly into brain. No infectious recovered dorsal root ganglia (DRG) multiple routes inoculation; however, DNA detected by PCR lumbosacral DRG at low copy number some mice. Importantly, recurrent vaginal shedding immunized guinea pigs. Intramuscular immunization outperformed subcutaneous all parameters evaluated, although individual differences were not significant, two immunizations more protective one. Immunized animals had reduced disease, titers, infection, genital lesions, HSV-2 DNA; protection incomplete. combined modality using C D subunit antigens pigs did totally eliminate lesions DNA. used an immunotherapeutic previously HSV-2-infected greatly frequency lesions. Therefore, safe, other injected high titer brain, efficacious prophylactic vaccine.