Abstract
BackgroundHerpes simplex virus type-1(HSV-1) and HSV-2 are important human pathogens that cause significant ocular and urogenital complications, respectively. We have previously shown that HSV-1 virions lacking glycoprotein K (gK) are unable to enter into neurons via synaptic axonal membranes and be transported in either retrograde or anterograde manner. Here, we tested the ability of HSV-1 (F) gK-null to protect against lethal challenge with either highly virulent ocular HSV-1 (McKrae strain), or genital HSV-2 (G strain). The gK-null virus vaccine efficiently protected mice against lethal vaginal infection with either HSV-1(McKrae) or HSV-2 (G).ResultsFemale mice were immunized via a single intramuscular injection with 106 PFU of the gK-null virus. Immunized mice were treated with Depo-Provera fourteen days after vaccination and were challenged via the vaginal route one week later. Ninety percent of mice vaccinated with the gK-null virus survived HSV-1 (McKrae) challenge, while 70% of these mice survived after HSV-2 (G) challenge. Moreover, all vaccinated mice exhibited substantially reduced disease symptoms irrespective of HSV-1 or HSV-2 challenge as compared to the mock vaccinated challenge group. T-cell memory immune responses to specific glycoprotein B (gB) and glycoprotein D (gD) peptide epitopes were detectable at 7 months post vaccination.ConclusionsThese results suggest that the highly attenuated, non-neurotropic gK-null virus may be used as an effective vaccine to protect against both virulent HSV-1 and HSV-2 genital infections and induce lasting immune responses.
Highlights
HSV-1 and HSV-2 are closely related viruses sharing 83% nucleotide homology [1]
We describe the use of a glycoprotein Kdeleted HSV-1 virus as an effective vaccine to protect against lethal challenge with HSV-1 and HSV-2
HSV-1 and HSV-2 challenge following vaccination with glycoprotein K (gK)-null The gK-null virus was constructed by deletion of the gK gene using double-red recombination in conjunction with the HSV-1 genome cloned into a bacterial artificial chromosome (Figure 1)
Summary
HSV-1 and HSV-2 are closely related viruses sharing 83% nucleotide homology [1] These viruses cause different spectrum of disease symptoms. HSV-1 is the causative agent of cold sores, herpetic whitlow, herpes keratitis and ocular infections [2]. It is a leading cause of infectious blindness in the United States [3]. 1 has been increasingly identified with genital herpes infections [5,6,7] Both HSV-1 and HSV-2 produce persistent lifelong infections by establishing latency in immune privileged sensory neurons [8]. The gK-null virus vaccine efficiently protected mice against lethal vaginal infection with either HSV-1(McKrae) or HSV-2 (G). T-cell memory immune responses to specific glycoprotein B (gB) and glycoprotein D (gD) peptide epitopes were detectable at 7 months post vaccination
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