Abstract |
Despite the development of highly effective prophylactic vaccines against human papillomavirus (HPV) serotypes 16 and 18, prevention of cervical dysplasia and cancer in women infected with high-risk HPV serotypes remains an unmet medical need. We report encouraging phase 1 safety, tolerability, and immunogenicity results for a therapeutic HPV16/18 candidate vaccine, VGX-3100, delivered by in vivo electroporation (EP). Eighteen women previously treated for cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) received a three-dose (intramuscular) regimen of highly engineered plasmid DNA encoding HPV16 and HPV18 E6/E7 antigens followed by EP in a dose escalation study (0.3, 1, and 3 mg per plasmid). Immunization was well tolerated with reports of mild injection site reactions and no study-related serious or grade 3 and 4 adverse events. No dose-limiting toxicity was noted, and pain was assessed by visual analog scale, with average scores decreasing from 6.2/10 to 1.4 within 10 min. Average peak interferon-γ enzyme-linked immunospot magnitudes were highest in the 3 mg cohort in comparison to the 0.3 and 1 mg cohorts, suggesting a trend toward a dose effect. Flow cytometric analysis revealed the induction of HPV-specific CD8(+) T cells that efficiently loaded granzyme B and perforin and exhibited full cytolytic functionality in all cohorts. These data indicate that VGX-3100 is capable of driving robust immune responses to antigens from high-risk HPV serotypes and could contribute to elimination of HPV-infected cells and subsequent regression of the dysplastic process.
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Authors | Mark L Bagarazzi, Jian Yan, Matthew P Morrow, Xuefei Shen, R Lamar Parker, Jessica C Lee, Mary Giffear, Panyupa Pankhong, Amir S Khan, Kate E Broderick, Christine Knott, Feng Lin, Jean D Boyer, Ruxandra Draghia-Akli, C Jo White, J Joseph Kim, David B Weiner, Niranjan Y Sardesai |
Journal | Science translational medicine
(Sci Transl Med)
Vol. 4
Issue 155
Pg. 155ra138
(Oct 10 2012)
ISSN: 1946-6242 [Electronic] United States |
PMID | 23052295
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Viral
- Papillomavirus Vaccines
- VGX-3100
- Vaccines, DNA
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Topics |
- Adult
- Antigens, Viral
(genetics, immunology, metabolism)
- Electroporation
- Female
- Human papillomavirus 16
(immunology)
- Human papillomavirus 18
(immunology)
- Humans
- Immunotherapy
(adverse effects, methods)
- Papillomavirus Vaccines
(immunology, therapeutic use)
- Vaccines, DNA
(immunology, therapeutic use)
- Uterine Cervical Dysplasia
(immunology, therapy)
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