Escherichia coli-Produced Human Papillomavirus Vaccine Shows High Efficacy Among Women in Phase 3 Trial

A human papillomavirus (HPV) vaccine produced by Escherichia coli was found to be well tolerated and highly efficacious against high-grade genital lesions and persistent infection, according to results of a study published in The Lancet Infectious Diseases.

This was an interim analysis of data captured from a multicenter, randomized, double-blind, phase 3 controlled trial conducted at 5 sites in China between 2012 and 2013. Women (N=7372) aged between 18 and 45 years with no history of sexually transmitted infection and who had between 1 and 4 lifetime sexual partners were randomly assigned in a 1:1 fashion to receive 3 doses of either E coli-produced bivalent HPV 16 and 18 vaccine or hepatitis E vaccine (control). The primary outcomes included efficacy of the HPV vaccine against HPV 16- and 18-associated high-grade genital lesions, including cervical intraepithelial neoplasia of grade 2 or higher (CIN2+), vulvar intraepithelial neoplasia of grade 2 or higher (VIN2+), and vaginal intraepithelial neoplasia of grade 2 or higher (VaIN2+); and persistent infection associated with HPV 16 or 18 for 6 months or longer.

Among patients in the vaccine (n=3689) and control (3683) cohorts, the mean age was 30.0 (SD, 7.4) and 29.9 (SD, 7.3) years, 80.9% and 81.8% were susceptible to HPV 16 at baseline, 89.5% and 89.4% were susceptible to HPV 18 at baseline, and 90.6% and 91.1% were negative for intraepithelial lesions or malignancy at baseline, respectively.

Vaccine efficacy against high-grade CIN2+, VIN2+, and VaIN2+ was 100.0% (95% CI, 67.2%-100.0%; P =.002) for protection against HPV 16- or 18-associated events; 100.0% (95% CI, 63.6%-100.0%; P =.0005) for protection against HPV 16-assoicated events; and 100.0% (95% CI, -3785.1% to 100.0%; P =1.000) for protection against HPV 18-associated events. Vaccine efficacy was not significant against VaIN2+ in the intention-to-treat analysis, which included patients in the vaccine (n=3612) and control (n=3600) cohorts who received at least 1 vaccine dose and had completed 1 follow-up visit.

Vaccine efficacy against persistent infection for 6 months or longer was 97.3% (95% CI, 89.9%-99.7%; P <.0001) for HPV 16- or 18-assoicated infections, 95.8% (95% CI, 84.1%-99.5%; P <.0001) for HPV 16-assoicated infections, and 100.0% (95% CI, 86.0%-100.0%; P <.0001) for HPV 18-associated infections. Vaccine efficacy was similar among patients included in the intention-to-treat analysis.

At month 7, 100% of women who were initially seronegative seroconverted for HPV 16 (n=116) and 18 (n=125) with geometric mean concentrations (GMCs) of 726.77 IU/mL and 435.47 IU/mL, respectively. At 66 months, 100% of women who were seropositive for HPV 16 (n=110) remained seropositive with GMCs of 71.42 IU/mL, and 98.3% who were seropositive for HPV 18 (n=118) remained seropositive with GMCs of 33.78 IU/mL.

The rate of severe adverse events was 7.2% for patients in the vaccine cohort and 7.9% for those in the control cohort. A total of 1260 women in the vaccine and 1263 in the control cohorts became pregnant, resulting in 840 and 898 births, respectively. No congenital anomalies or pregnancy complications were reported.

Limitations include insufficient power and the exclusion of women with more than 4 lifetime sexual partners.

According to the researchers, “the E coli-produced bivalent HPV 16 and 18 vaccine is well tolerated, immunogenetic, and highly efficacious in preventing high grade genital lesions and persistent infection associated with HPV 16 and 18.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.