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:

• codon-modification
• DNA vaccine
• Genital herpes
• healthy volunteers
• HSV-2
• polynucleotide vaccine
• ubiquitination

Disclosure of potential conflicts of interest

JLD, BL, WPW, NF and YX have share options in Admedus Vaccines Pty Ltd. IHF is an inventor on the patent US 2011/0287039 A1, “Expression system for modulating an immune response” and WO 02/083181 A1, “Novel compositions and uses therefor” and is a director and shareholder in Admedus Vaccines Pty Ltd to which these patents have been assigned. JLD is also an inventor on patent US 2011/0287039 A1. PG is an employee of Q-Pharm, which was contracted by Admedus Vaccines Pty Ltd to carry out the trial.

Acknowledgments

We would like to thank: Dr. Suzanne Elliott and her dedicated staff of Q-Pharm Pty Ltd.; Ms. Janette Taylor and Professor Anthony Cunningham at the Westmead Institute for Medical Research for conducting the screening tests; Dr Daniel Watterton and Professor Paul Young at the University of Queensland for carrying out the neutralisation assay; and the trial subjects, who made the study possible.