Safety of an Escherichia coli-expressed bivalent human papillomavirus (types 16 and 18) L1 virus-like particle vaccine: an open-label phase I clinical trial

Abstract

An Escherichia coli-expressed recombinant bivalent human papillomavirus (types 16 and 18) vaccine candidate has been shown to be safe and immunogenic in preclinical trials. The safety of this vaccine was analyzed in an open-label phase I clinical trial in Jiangsu province, China. Thirty-eight healthy women from 18 to 55 y of age were enrolled and vaccinated at 0, 1, and 6 mo. Adverse events that occurred within 30 d after each injection and serious adverse events that occurred throughout the study were recorded. In addition, blood parameters were tested before and after each injection. All but one woman received all 3 doses. Thirty-two (84.2%) of the participants reported adverse events, all adverse events of which were mild, of short duration and resolved spontaneously. No serious adverse events occurred during the study. Changes in blood parameters after each injection were random, mild, and not clinically significant. These preliminary results show that a new Escherichia coli-expressed recombinant HPV 16/18 bivalent vaccine is well tolerated in healthy women and support further immunogenicity and efficacy studies for this HPV vaccine candidate.

Keywords: clinical trial; human papillomavirus; phase I; safety; vaccine.

Figures

Figure 1. Trial profile. One participant withdrew from the study before her third dose because she had moved away from the study area.

Figure 2. Age distribution of the participants.

Figure 3. Solicited local and systemic adverse events, unsolicited AEs and SAEs after vaccinations. The x-axis shows the number of participants experiencing AEs, with the highest severity of AEs experienced by each participant after each vaccination shown. Solicited AEs were monitored for seven days. Unsolicited AEs were monitored for 30 d. SAEs were monitored throughout the 7 months’ study. AE: adverse event; SAE: serious adverse event.

Figure 4. Blood index fluctuations after the first, second, and third vaccinations. The x-axis shows the number of participants who experienced changes in blood parameters. For each participant, these changes were determined by comparing the results of paired blood samples obtained before and 2 d after each vaccination. The fluctuations were classified into three categories: “remaining” indicated no grade change observed; “worsen” indicated a change from normal to abnormal or an increase in grade; and “improving” indicated a change from abnormal to normal or a decrease in grade. a, routine blood test; b, blood coagulation function; c, liver function; d, kidney function; e, other indexes.

Figure 5. Transmission electron micrograph of HPV16 and HPV18 L1 VLP ( × 25,000, Bar = 200 nm). (A). HPV16 L1 VLP; (B). HPV18 L1 VLP.