Safety and Comparative Immunogenicity of an HIV-1 DNA Vaccine in Combination with Plasmid Interleukin 12 and Impact of Intramuscular Electroporation for Delivery
Background. DNA vaccines have been very poorly immunogenic in humans but have been an effective priming modality in prime-boost regimens. Methods to increase the immunogenicity of DNA vaccines are needed.
Methods. HIV Vaccine Trials Network (HVTN) studies 070 and 080 were multicenter, randomized, clinical trials. The human immunodeficiency virus type 1 (HIV-1) PENNVAX®-B DNA vaccine (PV) is a mixture of 3 expression plasmids encoding HIV-1 Clade B Env, Gag, and Pol. The interleukin 12 (IL-12) DNA plasmid expresses human IL-12 proteins p35 and p40. Study subjects were healthy HIV-1–uninfected adults 18–50 years old. Four intramuscular vaccinations were given in HVTN 070, and 3 intramuscular vaccinations were followed by electroporation in HVTN 080. Cellular immune responses were measured by intracellular cytokine staining after stimulation with HIV-1 peptide pools.
Results. Vaccination was safe and well tolerated. Administration of PV plus IL-12 with electroporation had a significant dose-sparing effect and provided immunogenicity superior to that observed in the trial without electroporation, despite fewer vaccinations. A total of 71.4% of individuals vaccinated with PV plus IL-12 plasmid with electroporation developed either a CD4+ or CD8+ T-cell response after the second vaccination, and 88.9% developed a CD4+ or CD8+ T-cell response after the third vaccination.
Conclusions. Use of electroporation after PV administration provided superior immunogenicity than delivery without electroporation. This study illustrates the power of combined DNA approaches to generate impressive immune responses in humans.
Kyle, I was expecting more from this article than what I see. I have full access to pubmed and a massive electronic database of journals. I found this journal of course but couldn't find the abstract or article. How did you find this? Thanks.
J Infect Dis. (2013)
First published online: July 8, 2013
1Infectious Diseases Division, Department of Medicine
2Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee
3Division of Infectious Disease, Department of Medicine, University of Alabama Medical Center, Birmingham
4Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
5Emory University, Atlanta, Georgia
6Department of Pathology and Laboratory Medicine, School of Medicine
7Department of Pathology, University of Pennsylvania, Philadelphia
8Inovio Pharmaceuticals, Blue Bell, Pennsylvania
9San Francisco Department of Health, California
10Laboratory of Infectious Disease Prevention, New York Blood Center, New York City
11University of Rochester School of Medicine and Dentistry, New York
12Profectus BioSciences, Tarrytown, New York
13Astellas Pharma US, Northbrook, Illinois
14Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes, Port au Prince, Haiti
15Division of Infectious Disease, Brigham and Women's Hospital, Boston, Massachusetts
16National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
Correspondence: Spyros A. Kalams, MD, Vanderbilt University Medical Center, 1161 21st Avenue South, MCN A2207, Nashville, TN 37232