Modeling the long-term antibody response of a hepatitis E vaccine.

BACKGROUND: The first commercialized hepatitis E vaccine, HEV 239, has been shown to be safe and highly immunogenic, the protection as well as the vaccine-induced anti-HEV maintained for at least 4.5 years. However, the longer term persistence of the vaccine-induced anti-HEV responses is unknown. METHODS: Two statistical models, the power-law model and the modified power-law model, were applied to predict the long-term antibody response of the HEV 239 vaccine. The models were fit using the anti-HEV IgG data from a modeling subpopulation of 1278 baseline seronegative vaccinees who seroconverted within one month after finishing the whole vaccination course in the phase 3 trial of HEV 239. In addition, antibody data from a validation subpopulation were used to validate the robustness of the derived models. RESULTS: In the vaccinees without pre-vaccination immunity, the power-law model and the modified power-law model estimated that the median duration of the detectable antibody (≥0.077 WU/ml) was 8 years and 13 years, respectively. The power-law model and the modified power-law model estimated that 50% of these vaccinees will maintain detectable levels of anti-HEV IgG for 8 years and >30 years, respectively. CONCLUSIONS: The recombinant hepatitis E vaccine HEV 239 is predicted to provide from 8 years to nearly life-long persistence of anti-HEV IgG above detectable levels. Model predictions are based on conservative mathematical assumptions. (NCT01014845).

Immunogenicity and safety of an E. coli-produced bivalent human papillomavirus (type 16 and 18) vaccine: A randomized controlled phase 2 clinical trial.

BACKGROUND: This study aimed to investigate the dosage, immunogenicity and safety profile of a novel human papillomavirus (HPV) types 16 and 18 bivalent vaccine produced by E. coli. METHODS: This randomized, double-blinded, controlled phase 2 trial enrolled women aged 18-25 years in China. Totally 1600 eligible participants were randomized to receive 90µg, 60µg, or 30µg of the recombinant HPV 16/18 bivalent vaccine or the control hepatitis B vaccine on a 0, 1 and 6 month schedule. The designated doses are the combined micrograms of HPV16 and 18 VLPs with dose ratio of 2:1. The immunogenicity of the vaccines was assessed by measuring anti-HPV 16 and 18 neutralizing antibodies and total IgG antibodies. Safety of the vaccine was assessed. RESULTS: All but one of the seronegative participants who received 3 doses of the HPV vaccines seroconverted at month 7 for anti-HPV 16/18 neutralizing antibodies and IgG antibodies. For HPV 16, the geometric mean titers (GMTs) of the neutralizing antibodies were similar between the 60µg (GMT=10,548) and 90µg (GMT=12,505) HPV vaccine groups and were significantly higher than those in the 30µg (GMT=7596) group. For HPV 18, the GMTs of the neutralizing antibodies were similar among the 3 groups. The HPV vaccine was well tolerated. No vaccine-associated serious adverse events were identified. CONCLUSION: The prokaryotic-expressed HPV vaccine is safe and immunogenic in women aged 18-25 years. The 60µg dosage formulation was selected for further investigation for efficacy. CLINICAL TRIALS REGISTRATION: NCT01356823.