27 GX-188E, A therapeutic HPV vaccine, in combination with imiquimod or IL-7-HYFC for treatment of HPV-16 or HPV-18 related cin 3: results from phase 2 study

Abstract Introduction Available human papillomavirus (HPV) vaccines could have an important primary role in cervical cancer prevention once their long-term immunogenicity and safety are evaluated at the population level. The aim of this study was to optimize an assay to be used in evaluating the long-term durability of HPV vaccine response following a pilot vaccination of adolescent girls in Ghana. Methods A rapid, high-throughput, indirect enzyme-linked immunosorbent assay (ELISA) was evaluated for the detection and quantitation of anti-HPV L1 (late expression protein: types 6, 11, 16 and 18) immunoglobulin G (IgG) in human serum (n = 89). The performance of the assay was evaluated using serum collected from a cohort of pre-adolescent girls (n = 49) previously vaccinated with a quadrivalent vaccine and non-immune serum obtained from age-matched controls (n = 40). Results The seroprevalence of anti-HPV IgG antibodies was significantly higher among vaccinated than unvaccinated girls for both HPV − 16 (63.3% vs. 12.5%; p < 0.001) and HPV − 18 (34.7% vs. 20.0%; p = 0.042), respectively. Thirty-six months after receiving the third dose of vaccine, significantly higher mean anti–HPV-16 (0.618 vs. 0.145), anti–HPV-18 (0.323 vs. 0.309), and anti–HPV-6 (1.371 vs. 0.981) antibody levels were measured, compared to unvaccinated girls (all p < 0.05). A correlation between optical density and antibody activity indicated assay sensitivity to increasing levels of antibody activity. Conclusion We have successfully developed and implemented a robust and sensitive assay for the evaluation of antibody responses among immunized adolescent girls for monitoring future large-scale HPV vaccination studies in low-income settings. Our results demonstrated greater immunoglobulin G antibody activity within serum drawn from adolescent girls immunized 36 months prior.

Download Full-text

Human Papillomavirus 16 (HPV 16) and HPV 18 Antibody Responses Measured by Pseudovirus Neutralization and Competitive Luminex Assays in a Two- versus Three-Dose HPV Vaccine Trial

Clinical and Vaccine Immunology ◽

10.1128/cvi.00489-10 ◽

2011 ◽

Vol 18 (3) ◽

pp. 418-423 ◽

Cited By ~ 30

Author(s):

Mel Krajden ◽

Darrel Cook ◽

Amanda Yu ◽

Ron Chow ◽

Wendy Mei ◽

...

Keyword(s):

Human Papillomavirus ◽

Hpv Vaccine ◽

Antibody Responses ◽

Hpv 16 ◽

Suitable Alternative ◽

Human Papillomavirus 16 ◽

Group 3 ◽

Group 2 ◽

Hpv 18 ◽

Group 1

ABSTRACTHuman papillomavirus 16 (HPV 16) and HPV 18 antibody responses in a 2- versus 3-dose HPV vaccine (Gardasil) trial were measured by a pseudovirus neutralizing antibody (PsV NAb) assay and by the Merck competitive Luminex immunoassay (cLIA). Eight hundred twenty-four female subjects assigned to three dosing regimens (group 1, 9 to 13 years old; 2 doses, months 0 and 6 [n= 259]; group 2, 9 to 13 years old; 3 doses, months 0, 2, and 6 [n= 260]; group 3, 16 to 26 years old; 3 doses, months 0, 2, and 6 [n= 305]) had postvaccine responses assessed 1 month after the last dose. Of 791 subjects with baseline and 7-month sera, 15 (1.9%) and 9 (1.1%) were baseline seropositive for HPV 16 and HPV 18, respectively. All baseline-seronegative vaccinees seroconverted to both HPV 16 and HPV 18. Mean anti-HPV 16 levels were similar for groups 1 and 2 (for PsV NAb,P= 0.675; for cLIA,P= 0.874), and levels for both groups 1 and 2 were approximately 2-fold higher than that for group 3 (for PsV NAb and cLIA,P< 0.001). Mean anti-HPV 18 levels were approximately 1.4-fold lower in group 1 than in group 2 (for PsV, NAbP= 0.013; for cLIA,P= 0.001), and levels for both groups 1 and 2 were approximately 2.0- to 2.5-fold higher than that for group 3 (for PsV NAb and cLIA,P< 0.001). Pearson correlation coefficients for the assays were 0.672 for HPV 16 and 0.905 for HPV 18. Most of the discordant results were observed at lower cLIA signals. These results suggest that the PsV NAb assay could be a suitable alternative to cLIA for the measurement of postvaccine antibody responses.

Download Full-text

Assessment of HPV 16 and HPV 18 antibody responses by pseudovirus neutralization, Merck cLIA and Merck total IgG LIA immunoassays in a reduced dosage quadrivalent HPV vaccine trial

Vaccine ◽

10.1016/j.vaccine.2013.09.007 ◽

2014 ◽

Vol 32 (5) ◽

pp. 624-630 ◽

Cited By ~ 20

Author(s):

Mel Krajden ◽

Darrel Cook ◽

Amanda Yu ◽

Ron Chow ◽

Qiang Su ◽

...

Keyword(s):

Hpv Vaccine ◽

Vaccine Trial ◽

Antibody Responses ◽

Hpv 16 ◽

Quadrivalent Hpv Vaccine ◽

Hpv 18

Download Full-text

Pembrolizumab plus GX-188E therapeutic DNA vaccine in patients with HPV-16-positive or HPV-18-positive advanced cervical cancer: interim results of a single-arm, phase 2 trial

The Lancet Oncology ◽

10.1016/s1470-2045(20)30486-1 ◽

2020 ◽

Vol 21 (12) ◽

pp. 1653-1660 ◽

Cited By ~ 1

Author(s):

Jin Won Youn ◽

Soo-Young Hur ◽

Jung Won Woo ◽

Yong-Man Kim ◽

Myong Cheol Lim ◽

...

Keyword(s):

Cervical Cancer ◽

Dna Vaccine ◽

Advanced Cervical Cancer ◽

Phase 2 ◽

Hpv 16 ◽

Phase 2 Trial ◽

Therapeutic Dna Vaccine ◽

Hpv 18

Download Full-text

Human papilloma virus (HPV) vaccine: Gardasil reactions

American Journal of BioMedicine ◽

10.18081/2333-5106/014-06/136-146 ◽

2014 ◽

Vol 2 (3) ◽

pp. 137-146

Keyword(s):

United States ◽

Cervical Cancer ◽

Hpv Vaccine ◽

Death Rate ◽

The United States ◽

Hpv Infection ◽

World Health ◽

Hpv 16 ◽

Night Sweats ◽

Hpv 18

The World Health Organization (WHO) as well as public health officials in Australia, Canada, Europe, and the United States recommend vaccination of young women against HPV to prevent cervical cancer, and to reduce the number of treatments for cervical cancer precursors. The death rate from cervical cancer in the United States is 3 per 100,000 and in 2011, about 12,000 women were diagnosed with cervical cancer and 4,000 died. In 2009, there were about 34,000 deaths from car accidents in the U.S. for a death rate of 11 per 100,000. HPV infection is extremely common; most sexually active people will be infected with HPV at some point in life. HPV infection usually causes no symptoms, but can cause genital warts and anal cancer in both women and men. The HPV vaccine prevents infection by the HPV types responsible for most cervical cancers. There are two available forms of the HPV vaccine: Cervarix; prevents infection by HPV-16 and HPV-18 and Gardasil; prevents infection by HPV-16, HPV-18, and also HPV-6 and HPV-11. There are many side events may caused by HPV vaccines such as; seizures, fatigue, strokes, dizziness, weakness, headaches, stomach pains, vomiting, muscle pain and weakness, joint pain, auto-immune problems, chest pains, hair loss, appetite loss, shortness of breath, heart problems, personality changes, insomnia, hand/leg tremors, arm/leg weakness, paralysis, itching, rashes, swelling, aching muscles, pelvic pain, nerve pain, menstrual cycle changes, fainting, swollen lymph nodes, night sweats, nausea, temporary vision/hearing loss. This topic review focused mainly on the side effects and health serious problems with Gardasil vaccine.

Download Full-text