An attenuated HSV-1 live virus vaccine candidate that is replication competent but defective in epithelial cell-to-cell and neuronal spread

Abstract

Live attenuated vaccines represent the most successful approach for the prevention of alphaherpesvirus infections, including varicella zoster virus, pseudorabies virus, and equine herpes virus 1. It is reasonable to consider that live virus vaccines may also be effective for the prevention of other alphaherpesviruses, such as herpes simplex virus 1 (HSV-1) and 2 (HSV-2). An HSV-1 mutant strain that is deleted in glycoprotein E (gE), NS-gEnull, is replication competent but is defective in spread from one epithelial cell to another, from epithelial cells to axons, and from the neuron cell body into axons. The defect in spread likely accounts for the favorable safety profile of the live virus vaccine candidate in mice. The NS-gEnull mutant is also defective in immunoglobulin G (IgG) Fc receptor binding, which is a process used by the virus to escape antibody attack. NS-gEnull when used as an immunogen is highly effective in providing protection against epidermal and vaginal challenge by wild-type (WT) HSV-1 and HSV-2. NS-gEnull represents a novel HSV-1 vaccine approach that retains replication competency while impairing virus spread at the inoculation site and in neurons. Only gE is deleted from the vaccine strain, ensuring that most viral antigens are presented to the host. This strategy is worth considering for prevention of HSV-1 and possibly HSV-2. © Springer Basel AG 2011.