An escalating dose study to assess the safety, tolerability and immunogenicity of a Herpes Simplex Virus DNA vaccine, COR-1

Abstract

This paper describes a single site, open-label Phase I clinical trial evaluating the safety, tolerability and immunogenicity in healthy volunteers of a herpes simplex polynucleotide vaccine that has previously been shown to enhance immunogenicity and protect against lethal herpes simplex virus type 2 (HSV-2) challenge in mice. Five escalating doses of the vaccine, COR-1, were given by intradermal injection to HSV-1 and 2 seronegative healthy individuals. COR-1 was found to be safe and well-tolerated; the only vaccine-related adverse events were mild. While vaccine-induced antibody responses were not detectable, cell-mediated immune responses to HSV-specific peptide groups were identified in 19 of the 20 subjects who completed the study, and local inflammation at the immunisation site was observed. This study indicates COR-1 has potential to be used as a therapeutic vaccine for HSV-2 infection.

Keywords: DNA vaccine; Genital herpes; HSV-2; codon-modification; healthy volunteers; polynucleotide vaccine; ubiquitination.

Figure 1.

Disposition of subjects. N = number of subjects.

Figure 2.

Injection site reactions. Scores corresponding to the injection site erythema size, measured 1 (A) and 2 (B) days after each vaccination, are plotted for subjects of cohorts that received 500 μg to 30 μg DNA vaccine. Note that the cohort which received 1 mg of DNA vaccine received 2 injections of 500 μg to both forearms. Scores of 1, 2, 3 and 4 were given for erythema measuring ∼0.5, ∼1.0, ∼1.5 and >1.5 cm, respectively.

Figure 3.

Pre-existing and vaccine-related cellular responses measured by IFN-γ ELISPOT. (A) Pre-existing responses to the gD2 peptide were determined using PBMCs taken at Visit 1 before the first vaccination. Responses were determined positive if X-(SD of X) – Y-(2xST of Y) > 10 (X: mean spot value; Y: mean spot value of no peptide control wells). (B) Number of subjects that were classified of having mounted a vaccine-related cellular immune response to gD2. Vaccine related positivity was accepted when the mean spot value was increased at least 2 fold compared to pre-existing responses in at least one peptide pool and at least one visit after vaccination.