Abstract
ABSTRACTThis 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.
Highlights
Genital herpes is a common sexually transmitted disease that results from infection of the genital mucosa with Herpes Simplex Virus type 2 (HSV-2) or, increasingly, by infection with HSV type 1 (HSV-1).[1,2,3] While for some the infection is mild, others experience frequent and debilitating outbreaks
Two subjects withdrew from the study after the first vaccine injection: one in the 10 mg COR-1 group and one in the 1 mg dose group
A large number of DNA vaccines have undergone clinical trial and their general safety demonstrated.[18]. Consistent with those studies, this Phase I clinical trial clearly demonstrates that 3 intradermal immunizations with COR-1 is safe and well-tolerated in humans at doses up to 1 mg, with no vaccine-related moderate or severe treatment emergent adverse events (TEAEs) or SAEs observed
Summary
Genital herpes is a common sexually transmitted disease that results from infection of the genital mucosa with Herpes Simplex Virus type 2 (HSV-2) or, increasingly, by infection with HSV type 1 (HSV-1).[1,2,3] While for some the infection is mild, others experience frequent and debilitating outbreaks. HSV infection can lead to encephalitis in newborn babies, or ocular disease (such as herpes stromal keratitis) and HSV infection is believed to facilitate the transmission of Human Immunodeficiency Virus type 1.4,5 While antiviral medications are available to reduce the duration and severity of the outbreaks, these drugs are expensive, cannot eliminate outbreaks or shedding, and do not prevent recurrence of lesions and the spread of disease. Despite a number of clinical trials of potential vaccines for genital herpes, none have been shown to effectively prevent herpes infection.[6,7,8] Chiron’s recombinant gB2/ gD2 subunit vaccine formulated with MF59 adjuvant, despite generating neutralising antibodies, was ineffective in reducing HSV-2 acquisition.[9] Another recombinant subunit vaccine, GSK’s gD2/ alum/ 3-O-deacylated-monophosphoryl lipid A vaccine showed initial promise as, while it did not prevent HSV-2 acquisition in men or HSV-1 seropositive women, it did reduce HSV-2 disease by 70% and HSV-2 infection by 40% in HSV-1 and -2 double seronegative women.[10] this finding was not replicated in a larger follow-up study 11 and the vaccine was only shown to have an effect on HSV-1 disease and acquisition
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