Methods: We infected mice by corneal scarification with serial dilutions of a clinical strain of HSV-1 (Bx31.1) to identify a sublethal dose associated with seroconversion. We then superinfected mice on the skin with HSV-2 and monitored for disease. Presence of virus in dorsal root ganglia (DRG), the site of HSV latency, was determined by quantitative PCR.
Results: Corneal infection with 10^4 PFU of HSV-1 resulted in disease in 18/29 (62%) mice and 13/18 survived. Seroconversion was documented in 9/13 survivors. Surviving mice were superinfected 2 weeks post-recovery with HSV-2. All of the mice developed signs of disease, but only 2/9 who were HSV-1+ died compared to 4/4 seronegative mice (p=0.02, Fisher exact test). HSV-2 DNA was detected in the DRG of 12/13 mice.
Conclusion: Sublethal HSV-1 corneal disease provides partial protection against HSV-2 superinfection and provides a model to test vaccine efficacy. We speculate that superinfection boosts preexisting nAb titers, a response consistent with immune repertoire freeze, but that ΔgD-2, because it elicits ADCC Abs, will overcome repertoire freeze and provide greater protection against HSV-2 superinfection.
B. C. Herold, X-vax: Grant Investigator , Research grant and Research support