9th Annual Meeting of the American Society of Gene Therapy

ILC Workshop: Genetic Vaccine Clinical Trials (Doug Jolly, PhD and Gwen Binder, PhD)

Dr. Alain Roland (Chair): Vical: Overview of gene-based vaccines

A gene based vaccine for salmon is newly approved. There are now 93 gene-based vaccine clinical trials worldwide. Vical has renewed their efforts in this area and is pursuing an HIV vaccine with IAVI using DNA injection or electroporation (Inovio). Vical is also developing an influenza vaccine and demonstrated cross protection in mice, including for H5N1, and in ferrets after high challenge (5000 ID₅₀).

Dr. Timothy Tobery: Merck: Adenoviral (Ad) vectors expressing HIV antigens as HIV vaccines

A prime boost approach with this agent doubles the response rate. This CTL generating vaccine induced lower acute and chronic viral load in 27 of 33 monkeys. A phase I trial demonstrated that preexisting Ad immunity can be overcome with higher vector doses of 10¹¹. A Phase II trial in South Africa in 3000 high-risk people is ongoing, and will examine cross-clade efficacy and the role of preexisting immunity.

Dr. Michael Fons: Inovio: Clinical Electroporation

Delivery occurs by DNA injection followed by electroporation, which delivers a square wave pulse of electricity intra-tumorally or intramuscularly between two needles. This induces transient pores in cell membranes, and enhances delivery 10-100 fold with little to no risk of integration. The level of discomfort is equivalent to a needle stick. Over 50 patients have been treated. Four ongoing trials are in cancer and preclinical studies are in HCV and HIV.

Dr. Julie Martin: Vaccine Research Center, NIH: Phase I West Nile Virus vaccine trial

The DNA-based vaccine is designed to elicit antibody to the envelope protein, which is known to be protective. Vaccine (4 mg) was administered intramuscularly to 15 volunteers at 0, 1 and 2 months by biojector. Follow-up is currently at 12 weeks in all patients and will continue to 6 months. Neutralizing antibodies were detected in all patients who received three doses.

Dr. Suzanne Epstein: Center for Biologics Evaluation and Research, FDA: Flu Vaccine

Historical data that suggested that previous flu infection provides some protection against a subsequent strain (heterosubtypic immunity). This data supports the utility of a cross protective vaccine based on non-variant flu proteins. Adoptive transfer from immunized mice to mice challenged with heterotypic virus reduced morbidity and mortality, and was related to CD4 and CD8 T cells only. Such a vaccine could be used to reduce morbidity of novel flu virus, while a protective vaccine is developed.