Therapeutic HPV16 and HPV18 vaccine ‘may eliminate infection’

Oct 15 2012

By Liam Davenport, medwireNews Reporter

A candidate vaccine against human papillomavirus serotypes 16 and 18 appears to induce robust immune responses to antigens, potentially leading to the elimination of virus-infected cells and regression of dysplasia, say US investigators.

"The data generated from this phase 1 trial of VGX-3100 are important in terms of the safety and tolerability of the DNA-plus-EP [electroporation] platform as well as in terms of the magnitude and types of immune responses generated," comment the researchers, led by Niranjan Sardesai (Inovio Pharmaceuticals, Blue Bell, Pennsylvania).

They write in Science Translational Medicine that the findings of the study open up "the likely use of this combined technology to treat or prevent other human infectious diseases and cancers."

For the study, 18 women previously treated for cervical intraepithelial neoplasia grade 2 or 3 were given three intramuscular doses of VGX-3100, a highly engineered plasmid DNA encoding E6/E7 antigens from HPV16 and HPV18, followed by EP. The vaccine was given at one of three doses: 0.6, 2.0, or 6.0 mg DNA per dose.

Adverse events were mild to moderate, and all injection sites resolved without sequelae. Any grade 3 adverse events were deemed unrelated to treatment. Furthermore, all laboratory abnormalities were mild or moderate and required no treatment. Pain scores decreased from 6.2/10 to 1.4/10 within 10 minutes of injection.

All participants developed antibody positivity to at least two vaccine antigens, while 94% had positivity to three antigens and 56% to all four antigens. The antibodies elicited against HPV16 and HPV18 E7 antigens were more robust than those elicited to E6 proteins. Nevertheless, antibody titers against the four vaccine antigens remained high 24 weeks after the last immunization.

Vaccine-induced HPV16 or HPV18 E6- or E7-specific cellular immune responses were seen in four of six participants who received the lowest vaccine dose, in five of six of those who received the intermediate dose, and in five of six of those who received the highest dose. Overall, 78% of participants mounted a cellular response to the vaccine, and 100% had a humoral response.

Finally, it was observed that the vaccines caused the induction of HPV-specific CD8-positive T cells that efficiently loaded granzyme B and perforin, and had full cytotoxic functionality.

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